Fibromuscular Dysplasia (Genetic Component)

Non-atherosclerotic, non-inflammatory arteriopathy of medium-sized and small arteries, predominant in women, with a multifactorial basis and minority familial aggregation, a common susceptibility locus in PHACTR1 and other association loci, and a rare monogenic form linked to COL5A1.

Literature and regulatory information updated: 31 October 2026.

0. Initial Reference Table

1. Introduction

1.1. Original description and evolution of the concept

Fibromuscular dysplasia (FMD) was described in 1938 and, in the 1960s and 1970s, classified according to angiographic and histopathological criteria that separated intimal, medial and perimedial fibroplasia [1, 2]. For several decades, knowledge of the disease was based on surgical specimens and small series of patients with renovascular hypertension, which led to it being considered a rare and almost exclusively renal cause of hypertension in young women [2]. The most significant advances came after 2009, with the US FMD registry and the French and European registries (ARCADIA, since 2010, and the European/International FMD Registry and Initiative, FEIRI, since 2015), which showed a systemic disease, often multivessel, with cerebrovascular involvement as frequent as renal involvement and with dissections and aneurysms in about 40% of patients [2, 26, 27, 34].

In 2014, an American Heart Association (AHA) scientific statement and a European consensus were published independently, with similar interpretations of the literature but slightly different terminologies ("focal" FMD in the AHA document and "unifocal" in the European document) [2, 35, 36]. In 2019, a committee commissioned by the Society for Vascular Medicine (SVM) and the "Hypertension and the Kidney" working group of the European Society of Hypertension (ESH) published the first international consensus, simultaneously in Vascular Medicine and the Journal of Hypertension, which harmonises North American and European practice and remains the reference document for adults; the authors stress that level I data are scarce and that most consensus points result from expert opinion [2].

1.2. Milestones of genetic research

Familial occurrence has been described since the 1960s in sisters with renovascular hypertension, and the first formal pedigree analysis, by Rushton in 1980, found other affected relatives in 12 of 20 families, with repeated vertical transmission, although without histological confirmation in the relatives [1]. Gladstien and colleagues concluded in the same year that the data were compatible with autosomal dominant inheritance of variable and often subclinical expression [1]. Candidate gene studies of connective tissue disorders (FBN1, ACTA2, SMAD3, TGFBR1/2, COL3A1) and the first exomes of small families did not identify a major gene, which steered research towards a complex model [2, 37].

In 2016, Kiando and colleagues identified the first susceptibility locus, the polymorphism rs9349379 in an intron of PHACTR1 (6p24), and in 2017 Gupta and colleagues showed that this same variant, associated with five vascular diseases, regulates at a distance the expression of the endothelin-1 gene (EDN1) [8, 38]. In 2021, the first meta-analysis of genome-wide association studies (GWAS) added the loci LRP1, ATP2B1 and LIMA1 and, by transcriptome-wide analysis, SLC24A3, estimating a SNP-based heritability of 0.43 [7]. In parallel, rare monogenic forms were described: loss of function of PTGIR (prostacyclin receptor) enriched in patients with FMD, biallelic YY1AP1 variants in Grange syndrome and, in 2020, the recurrent variant COL5A1 c.1540G>A p.(Gly514Ser), which defined the first monogenic form of multifocal FMD (OMIM #619329) [3, 4, 37].

1.3. Definition, classification and current nomenclature

The international consensus adopts the European definition: an idiopathic, segmental, non-atherosclerotic and non-inflammatory disease of the musculature of the arterial walls, leading to stenosis of small and medium-sized arteries, with lesions that may be symptomatic or silent and haemodynamically significant or not [2]. The histological classification is no longer applicable in practice, because tissue is rarely available since the advent of endovascular therapy, and has been replaced by a binary angiographic classification: multifocal FMD, with alternating stenoses and dilatations ("string of beads"), usually in the mid and distal portions of the artery; and focal FMD, with an isolated stenosis in any segment [2, 23]. Diagnosis requires at least one focal or multifocal lesion; isolated aneurysm, dissection or tortuosity is not sufficient but, when it coexists in another bed with a typical lesion, it counts as multivessel involvement [2].

FMD is, by definition, a diagnosis of exclusion of other arteriopathies, including monogenic ones: the presence of a known hereditary syndrome (vascular Ehlers-Danlos, Loeys-Dietz, neurofibromatosis type 1, Williams, Alagille, Grange) removes the patient from the category of idiopathic FMD, even if the lesions are indistinguishable on imaging [2, 39]. The form associated with COL5A1 occupies an intermediate position, because the arterial phenotype is that of multifocal FMD, but OMIM classifies it as a separate Mendelian entity [3]. In children, FMD differs from the adult form in histology (intimal fibroplasia predominates), distribution and the proportion of boys, and the terms "childhood cerebral and systemic arteriopathies" and "aorto-renal dysplasia" have been proposed for the focal paediatric renal form [39, 40]. A 2026 review by the European group proposed a more detailed classification of FMD and related diseases, beyond the focal/multifocal distinction, presented as a research tool and common language among clinicians [41].

The scope of this article is the genetic component of FMD in adults and children: the polygenic architecture, familial aggregation, rare monogenic forms and the genetic and clinical overlap with spontaneous coronary artery dissection (SCAD) and spontaneous cervical artery dissection (CeAD). The monogenic arteriopathies (Grange syndrome, vascular Ehlers-Danlos, Loeys-Dietz, neurofibromatosis type 1, Williams-Beuren, Alagille) are included only as differential diagnoses.

2. Molecular Genetics and Pathophysiology

2.1. Arterial lesion and pathophysiology

The most frequent lesion is medial fibroplasia, which corresponds to the multifocal angiographic phenotype: smooth muscle cells lose their elongated shape and their arrangement perpendicular to flow, islands of fibrous tissue appear between them and the internal elastic lamina shows breaks [37]. Intimal fibroplasia, more associated with focal stenoses, represents less than 5% of specimens in adults, but predominates in children: in a series of 81 children with FMD and arterial ischaemic stroke, 27 had histological confirmation, with intimal fibroplasia in 89% and none with the medial fibroplasia typical of adults [39]. In the classical pathology-based distribution, taken up by the French national protocol, medial fibroplasia accounts for 60–70% of lesions ("beaded" appearance, with areas of fibrous hypertrophy of the media and rupture of the internal elastic lamina, mainly around 40 years of age), perimedial or subadventitial fibroplasia for 10–20% (tubular stenosis due to hyperplasia of the extracellular matrix in the outer layers of the media, which compresses the adventitia and narrows the lumen) and intimal fibroplasia for about 5% (unifocal stenosis due to circumferential thickening of the intima, without involvement of the other tunicae) [33]. Renal artery stenosis reduces perfusion pressure, activates the renin-angiotensin-aldosterone system and raises blood pressure; in multifocal FMD, however, renal flow and renin may be normal and the disease is often bilateral, which makes renal vein renins of little value [2, 31].

The changes are not limited to the stenosed segments. High-resolution echo-tracking studies found thicker carotid and radial arteries and echoacoustic heterogeneity in arteries without apparent lesions, and a physiological study showed reduced endothelium-independent dilatation and a smaller brachial artery diameter, which suggests a systemic alteration of arterial tone and structure [37]. Increased secretion of TGF-β1 and TGF-β2 by dermal fibroblasts and raised plasma levels of these factors, a plasma signature of 37 proteins and 10 lipids (confirmed in a validation cohort), collagen degradation products in urine and intense expression of progesterone receptors in the nuclei of smooth muscle cells of operated renal arteries have been described [2, 21, 37]. These findings have not yet translated into biomarkers for clinical use [37].

2.2. Inheritance model: from pedigree to complex model

In modern registries, only 1.9–7.3% of patients report an affected relative; in the US registry, patients frequently reported a family history of stroke (53.5%), aneurysm (23.5%) and sudden death (19.8%), but only 7.3% had documented FMD in a first- or second-degree relative [2, 34]. Family analyses have been limited by the small size of families (pairs of sisters, mother and daughter), by incomplete penetrance, estimated at about 0.5, and by underdiagnosis of subclinical disease, since invasive imaging is not justified in asymptomatic relatives [2, 37]. Cases of renal FMD in monozygotic twin pairs and in sibships have been described, and the French protocol estimates that familial forms account for about 5% of cases, a value within the range of the registries [33]. The prevalence of asymptomatic FMD in the population (about 3–6% in imaging series), the influence of environmental and hormonal modifiers and the absence of a major gene in family exomes point to a complex architecture, with a majority contribution from common variants of small effect and a minority of rare monogenic forms [2, 37]. Family history is therefore a risk factor, but does not define a Mendelian pattern in most patients. The reference table records the two patterns described: multifactorial in most cases and autosomal dominant with incomplete penetrance in some families and in the form associated with COL5A1 [1, 3].

A study with carotid echo-tracking found a higher "arterial score" in familial and sporadic patients than in controls and intermediate values in unaffected relatives, which suggests a shared subclinical arterial phenotype, but with limited ability to distinguish the medial thickening of FMD from the intima-media thickening of atherosclerosis [37].

2.3. Common variants: the susceptibility loci

The first locus was identified in a two-stage study of about 26,000 common variants in 249 patients and 689 controls, replicated in 1154 cases (85% women) and 3895 controls from four studies: the polymorphism rs9349379, in the third intron of PHACTR1 [8, 37]. The 2021 meta-analysis analysed about 5.5 million variants in 1556 patients with multifocal FMD and 7100 controls, all of European ancestry, and estimated a SNP-based heritability of 0.43 (standard error 0.14), compatible with a substantial polygenic basis [7]. A GWAS restricted to women (1421 cases) reproduced the same four loci; the number of men (135) did not allow a separate analysis, and there was no signal on the X chromosome [7, 37].

Table sources: [7, 37]. In GRCh38, rs9349379 is located at NC_000006.12:g.12903725, and the FMD risk allele (A) is the reference allele, present on about 60% of chromosomes of European ancestry [37, 42].

All FMD loci are also blood pressure loci, and the overall genetic correlation between FMD and systolic and diastolic pressure is positive; the associations persist when stratified by hypertension or conditioned on the genetics of systolic pressure, which indicates a contribution of the arteriopathy itself [7]. FMD has a positive genetic correlation with migraine (rg 0.28), intracranial aneurysm (rg 0.36) and aneurysmal subarachnoid haemorrhage (rg 0.35), high but non-significant with CeAD (rg 0.67), and negative with coronary artery disease (rg −0.31) and myocardial infarction (rg −0.30), independent of blood pressure [7]. This opposition is reproduced at PHACTR1: the rs9349379-A allele increases the risk of FMD, CeAD, SCAD and hypertension, but the G allele is associated with a higher risk of atherosclerotic coronary artery disease, in which PHACTR1 is among the more than 160 loci of small effect [37, 43]. In the CeAD GWAS (1393 cases and 14,416 controls), the G allele was associated with a lower risk (OR 0.75; 95% CI 0.69–0.82) [44].

2.4. PHACTR1, endothelin-1 and the mechanisms of the loci

PHACTR1 encodes a phosphatase and actin regulator that binds G-actin through RPEL motifs and regulates the phosphatase PP1 (PPP1CA), controlling stress fibre formation, motility and contractility of smooth muscle cells [12, 37]. rs9349379 lies in an arterial wall-specific regulatory element, interferes with the binding of MEF2 transcription factors and is an eQTL for PHACTR1 in artery, macrophages, fibroblasts and stem cell-derived endothelial cells [37]. In CRISPR-edited stem cell-derived endothelial cells, the variant regulates the expression of EDN1, located 600 kb upstream, and the G allele was associated with higher plasma endothelin-1 in healthy individuals, in angina and in SCAD, without replication in patients with FMD [37, 38]. Chromatin accessibility in the region is high in smooth muscle cells and macrophages, but low in endothelial cells, where EDN1 is transcribed, so the effector gene at the locus remains under discussion [37, 38].

The target genes of the other loci converge on arterial contraction and intracellular calcium homeostasis: ATP2B1 encodes a plasma membrane calcium pump whose deletion in mouse smooth muscle raises blood pressure through vasoconstriction; SLC24A3 encodes a sodium/calcium/potassium exchanger involved in vascular contraction, expressed less in arteries of women than of men and regulated by oestradiol and progesterone in the rodent uterus; LRP1 is an endocytic receptor that regulates the extracellular matrix and whose deletion in smooth muscle alters contraction, disrupts the elastic lamina and favours aneurysms [7, 37]. The dominant mechanistic hypothesis is altered vascular contraction or deficient relaxation, to which oestrogens, which are vasodilators and activators of prostacyclin synthesis, might respond differently in women [37].

The same PHACTR1 gene has a Mendelian phenotype unrelated to FMD: heterozygous de novo missense variants in the RPEL3 domain cause developmental and epileptic encephalopathy type 70 (DEE70, OMIM #618298), with infantile spasms, through a dominant-negative effect on neuronal migration [12]. The rs9349379 genotype is a small shift in population risk, does not diagnose FMD, does not predict DEE70 and should not be reported as a Mendelian result [2, 12, 30].

2.5. Monogenic forms and rare variants

The variant COL5A1 NM_000093.5:c.1540G>A p.(Gly514Ser) (GRCh38 NC_000009.12:g.134750587G>A) was identified in four unrelated probands of Central European ancestry, who share a 160.1 kb haplotype, suggestive of a common founder [3, 4, 10]. The substitution affects the penultimate glycine of the first triple-helix repeat of the interrupted collagenous region, in exon 12, and is absent from gnomAD [4, 9]. The probands presented with stroke due to carotid FMD with dissecting aneurysms (man aged 54 years), rupture of an iliac dissecting aneurysm (woman aged 44 years), infarction due to SCAD (woman aged 52 years) and hypertension with pulmonary artery aneurysm (woman aged 64 years); all had vertebral and carotid tortuosity, and only one met the 2017 criteria for classical Ehlers-Danlos, although hyperextensible skin, hypermobility, atrophic scars and postoperative dehiscence were present in several [3]. In family 1, the 24-year-old daughter and the 40-year-old nephew, both carriers, had hyperextensible skin and hypermobility, without dissection, which documents incomplete arterial penetrance [3]. In a cohort of 264 patients with multifocal FMD, the same variant and six other rare COL5A1 variants predicted to be deleterious were found (≈2.7%), associated with arterial dissections (p = 0.005), and none in 284 controls [3, 4]. In ClinVar, the c.1540G>A variant has conflicting classifications of pathogenicity (VCV000236997, last evaluated in December 2024) [45].

In an exome study of families and sporadic cases from the Hôpital Européen Georges-Pompidou, followed by sequencing in about 1000 patients from Europe and the US and exomes of 264 US patients, six unrelated patients, all women, had loss-of-function variants in PTGIR, with significant enrichment compared with gnomAD; the missense variant NM_000960.4:c.200T>C p.(Leu67Pro) reduced sensitivity to iloprost in functional assays [10, 37]. The variant described in the 2022 review as "p.Glu163*" corresponds, according to VariantValidator, to NM_000960.4:c.487C>T p.(Gln163Ter), a notation matching that of another review (Q163X); it was observed in a patient with FMD and SCAD [10, 46]. The first exomes of 16 familial cases (seven families) found no gene shared by three or more families, and extension to 249 sporadic cases showed a nominal association, yet to be replicated, for MYLK, OBSCN, DYNC2H1 and RNF213 [37].

Biallelic loss-of-function variants in YY1AP1 cause Grange syndrome, with FMD-like arterial stenoses, focal and multifocal; in 286 patients with sporadic multifocal FMD, one heterozygous truncating variant was found (none in 282 controls), and the heterozygous mother of three affected siblings had refractory hypertension due to renal artery stenosis, which led to the proposal of susceptibility through haploinsufficiency, not yet demonstrated [1, 37].

2.6. Environmental, hormonal and mechanical factors

Smoking is associated with renal FMD in case-control studies (current smokers OR 2.5–4.05; ever smokers OR 1.8–4.1); smokers with multifocal FMD are diagnosed earlier, have more renal asymmetry and more interventions and, in the US registry, more aneurysms [2]. Despite the female predominance of about 9:1 in the multifocal form, no causal relationship with oral contraceptives or hormone therapy has been demonstrated, and the genetic evidence identified no signal on the sex chromosomes [2, 37]. Renal mobility (nephroptosis) has been associated with FMD without a demonstrated major contribution, and mechanical factors may explain the predilection for the right renal artery, the mid-distal internal carotid and the external iliac artery [2]. The French protocol also lists, among the associated factors without a demonstrated causal role, an immunological factor (association with the HLA-DRw6 antigen, described in older series), alongside mechanical, hormonal, smoking-related and genetic factors [33].

2.7. Pleiotropy with arterial dissection and penetrance

FMD, SCAD and CeAD share loci (PHACTR1, LRP1), female predominance and clinical coexistence, but differ in part in their genetic architecture. The SCAD GWAS (1917 cases and 9292 controls) identified 16 loci, with a SNP-based heritability of about 0.70, genes linked to the extracellular matrix and a specific locus in the tissue factor gene F3 (rs1146473, OR 1.32), and several variants with an effect diametrically opposite to that in coronary artery disease [11]. Rare variants in fibrillar collagens and in connective tissue disease genes appear more in SCAD than in FMD, in which dissection within beds with typical lesions is rare; variants in Loeys-Dietz syndrome genes are enriched in SCAD but not in severe FMD [37, 47]. In all forms, expression is variable: families with members with hypertension only, others with dissection and carriers without demonstrable arterial disease [1, 3].

3. Clinical Spectrum and Manifestations by System

3.1. Data sources and what they measure

Almost all clinical data come from referral-centre registries, in which patients were studied with selective or systematic imaging, which overestimates the symptomatic and severe forms and underestimates the silent forms. The US registry included 1885 adults in 2018 (94.7% women; mean age at diagnosis 53.3 years) and the European/International registry 609 (83.3% women; 45.8 years); FEIRI published in 2021 the characterisation of 1022 patients from 22 countries (82% women, 88% Caucasian, age at diagnosis 46 ± 16 years, 12% aged 65 years or older; hypertension in 86%, multifocal FMD in 72% and multivessel disease in 57%) [2, 22]. The differences between registries reflect recruitment: the European registry included more hypertension centres and less cerebrovascular imaging, which explains less multivessel disease and more focal FMD [2].

Source: tables 4 and 5 of the international consensus [2]; not all patients underwent brain-to-pelvis imaging and the US registry had no central review of images.

3.2. Renal territory and hypertension

Hypertension is the most frequent manifestation (67–86% in the registries) and the usual route to diagnosis of renal FMD, whose typical phenotype is that of a middle-aged white woman with hypertension and a family history of hypertension; the renal arteries are involved in about 75% of patients in the US and ARCADIA registries [2, 22]. In the summary of the French protocol, renal lesions are bilateral in more than half of cases, the multifocal "beaded" appearance is seen on more than 80% of angiograms, mostly in women between 30 and 50 years of age, and hypertension may be accompanied by a lumbar bruit, renal size asymmetry or hypokalaemia [33]. The delay between onset of hypertension and diagnosis is, on average, nine years, which allows superimposed essential hypertension to develop and reduces the likelihood of cure after revascularisation [37]. Other renal presentations are a small unilateral kidney, an abdominal bruit, renal artery dissection with renal infarction (initial presentation in 3.1% in the US registry and more frequent in men) and, rarely, renal failure [2, 30]. In a French series of 186 renal infarctions, the predominant lesions were atherosclerosis (34.4%), dissecting haematoma (23.2%) and FMD (19.2%) [2].

The focal and multifocal forms correspond to distinct clinical phenotypes. In a series of 337 patients with renal FMD (82% multifocal), the unifocal form was diagnosed earlier (median 30 vs 49 years), with earlier hypertension (26 vs 40 years), more men (female:male ratio 2:1 vs 5:1), higher initial blood pressure (157/97 vs 146/88 mmHg), more smoking (50% vs 26%), more unilateral lesions (79% vs 38%) and renal asymmetry (33% vs 10%), more revascularisation (90% vs 35%) and a higher rate of cure of hypertension after revascularisation (54% vs 26%) [23].

3.3. Cerebrovascular territory

With systematic imaging, cervical FMD is as frequent as renal FMD; it mainly affects the mid-distal extracranial internal carotid and the vertebral arteries, and unruptured aneurysm is the main intracranial manifestation [2]. The most common manifestations are headache (8–52% in the series; significant headache in 67.5% and daily headache in 27.4% in the US registry), pulsatile tinnitus (17–23% as a presenting symptom; 22–27% prevalence) and dizziness; migraine affects 28–38% of patients, but leads to fewer than 10% of diagnoses [21, 30, 37]. A systematic review of 119 studies estimated, in cerebrovascular FMD, CeAD in 7–17%, saccular intracranial aneurysm in 7%, ischaemic stroke in 7–10%, transient ischaemic attack (TIA) in 5–12%, subarachnoid haemorrhage in 2–3% and intracerebral haemorrhage in 0.01% [21]. In the US registry, 12.9% of women had an intracranial aneurysm, more than half with multiple aneurysms, 43% measuring 5 mm or more and 19% in the posterior circulation [2, 48]. The French protocol places the age at diagnosis of symptomatic cervicocranial FMD around 50 years, includes retinal ischaemic events among the presentations and points out that, in older series, a significant proportion of cases were findings on angiography performed for another indication [33].

The relationship with CeAD is bidirectional. In the US registry, 26% of patients had an arterial dissection, mainly carotid or vertebral [2]. In the Italian IPSYS cohort, 103 of 1283 patients (8.0%) with a first spontaneous CeAD had cerebrovascular FMD, associated with migraine (OR 1.78), intracranial aneurysms (OR 8.71) and less prior minor trauma; FMD (HR 3.40; 95% CI 1.58–7.31) and migraine predicted recurrence [29]. In a cohort from three US centres (2018–2023), 97 of 1632 patients with CeAD (6%) had FMD; 33% had multiple dissections, associated with younger age and the classic "beaded" appearance (OR 3.06), 27% had aneurysms and, over 5 ± 2.5 years, 13% had a new dissection and 28% cardiovascular events [49]. Risk factors for presentation with CeAD are male sex, age over 50 years, migraine, hypertension and involvement of three or more beds [21, 22].

Carotid web, an endoluminal membrane of the bulb described mainly in Black and Afro-Caribbean patients, has been classified by some as atypical intimal FMD and is associated with embolic stroke, but the consensus considers it probably a distinct entity [2, 21].

3.4. Visceral, peripheral and aortic territories

Visceral involvement (coeliac trunk, hepatic, splenic, mesenteric arteries) occurs in 17.5–19.3% of patients studied and is associated with more aneurysms (41.2% vs 19.7%) and dissections (35.6% vs 20.6%); it presents with postprandial pain, mesenteric ischaemia, a bruit or spontaneous hepatic artery dissection with shock [2]. Symptomatic mesenteric stenoses may cause nausea, abdominal pain and weight loss; as these presentations are more often atherosclerotic, a search for FMD is justified in a young patient without risk factors or atheromatous plaques [33]. Lower-limb FMD is usually multifocal, bilateral and asymptomatic, in the external iliac arteries, and upper-limb FMD mainly affects the brachial artery, with digital ischaemia, arm claudication, Raynaud phenomenon and blood pressure asymmetry [2]. Aortic involvement was long questioned: in a series of 360 patients with multifocal FMD and complete aortic imaging, 10.0% had aortic findings (ectasia 4.7%, aneurysm 2.2%, congenital anomalies 2.5%, acute aortic syndrome less than 1%), associated with male sex and non-aortic aneurysms, and tests for hereditary aortopathy in nine of these patients were negative [50]. A systematic review brought together 34 patients with aortic FMD, mainly focal stenosis, histologically confirmed in 27 [51].

3.5. Coronary arteries and spontaneous coronary artery dissection

SCAD has a female predilection above 90%, occurs in about 10% of cases during or after pregnancy, accounts for 10–25% of myocardial infarctions in women under 50 years and for 50% of postpartum infarctions, and results from a false lumen in the outer third of the media that compresses the true lumen [2, 28]. Extracoronary FMD is found in 16% to 62.7% of patients with SCAD, depending on the method: 31.8% in a British series of 173 patients with blinded MR angiography (multivessel in 29.1% of these), with aneurysms in 7.5% and no primary extracoronary vascular events in five years, and 32.1% in a Polish series of 109 patients with CT angiography, with silent aneurysms in 23.2% [2, 25, 52]. In the Polish series, FMD was associated with type 2a SCAD (OR 2.53) and with pregnancy-associated SCAD [52]. Conversely, SCAD is rare in FMD: 2.7% of all patients in the US registry and 1–3% in more recent data from the consensus authors [2, 30]. Histological coronary FMD (aorto-ostial left main stem, sinus node and atrioventricular node arteries) is associated with sudden death in post-mortem reports, but appears to be an entity distinct from typical SCAD; it has been described as a cause of death in Costello syndrome [2, 19].

3.6. Differences by sex and age

Men represent 10–20% of patients, are diagnosed younger, and have more focal FMD, more dissections and more renal complications (dissection, infarction, renal failure) [22, 30]. Patients aged 65 years or older have more multifocal FMD, lower renal function and more coexisting atherosclerosis [22]. In FEIRI, independent predictors of multivessel disease were age at diagnosis, stroke, the multifocal subtype, the presence of aneurysm or dissection and a family history of FMD; of aneurysms, multivessel and multifocal disease; of dissections, age, male sex, stroke and multivessel disease [22].

3.7. Paediatric FMD

In the 33 children of the US registry (mean age at diagnosis 8.4 ± 4.8 years, from 16 days to 17 years), compared with 999 adults, there were more boys (42.4% vs 6%), hypertension in all, headache in 55%, renal involvement in 97% (vs 69.7%), less extracranial carotid involvement (23.1% vs 73.3%) and more mesenteric (38.9% vs 16.2%) and aortic involvement (26.3% vs 2.4%) [24]. In a series of 25 children with renovascular FMD from a US paediatric centre included in the same registry (mean age 7 ± 4.9 years, from 4 months to 17 years), 48% were boys, 40% were not Caucasian, all were hypertensive, 48% had headache, only 12% had a renal bruit, 8.7% had a family history of FMD and none had pulsatile tinnitus, neck pain or stroke; focal FMD (at one or several sites) predominated over multifocal FMD (11 of 25 children) [53]. The first paediatric meta-analysis (nine studies, 218 children, all with renal FMD, mean age 11.7 years) found 52% girls, focal FMD in 66.6%, multivessel disease in 19.1% despite incomplete screening, aneurysms in 15.3%, dissections in 1.7% and mid-aortic syndrome in 6.3%; 93.7% were revascularised [54]. In children, intracranial lesions are more frequent and extracranial lesions less frequent than in adults, there is more family history of FMD or genetic arteriopathies, and stroke occurs in 0–3% [21]. Renovascular hypertension accounts for 5–10% of paediatric hypertension, and FMD is the most common cause of renal artery stenosis in children; it may present as hyponatraemic hypertensive syndrome, with severe hypertension, hyponatraemia, hypokalaemia, metabolic alkalosis and polyuria [55].

3.8. Natural history and treated disease

The evolution of the lesions is poorly understood: multifocal FMD is rare in children, which suggests that it arises mainly in young adults, but longitudinal studies are lacking [37]. Aneurysms and dissections are present in 41.7% of patients at the time of diagnosis in the US registry, and patients with dissection are younger (48.4 vs 53.5 years) and have more ischaemic events [26]. Systematic imaging reveals additional lesions: in ARCADIA, 48.0% of the 469 patients had FMD in more than one bed and 66.3% had lesions (including aneurysms and dissections) in more than one bed; in a series with chest-to-pelvis CT angiography, 48.7% had new FMD lesions, 18.6% new aneurysms and 2.7% new dissections [2, 27]. The risk of new lesions in previously normal beds appears low, according to the consensus authors [30]. In a population-based study of stroke/TIA in Alberta (2016–2017), cerebrovascular FMD was found in 0.86% of patients with CT angiography or MR angiography; at five years, recurrence of stroke/TIA was 22.9% and mortality 28.5%, with no significant difference compared with patients without FMD after adjustment (HR 1.54; 95% CI 0.77–3.11), in a population with a median age of 74 years [56]. Data on treated disease (angioplasty, antiplatelet therapy) are observational.

4. Clinical Recognition and Warning Signs

4.1. When to suspect in adults

Suspicion arises from combinations of signs in a patient without atherosclerotic risk factors, typically a middle-aged woman: early or resistant hypertension, pulsatile tinnitus, a cervical or abdominal bruit, or an unexplained vascular event, such as subarachnoid haemorrhage, carotid or vertebral dissection, renal infarction, mesenteric ischaemia, or early-onset or severe pre-eclampsia or gestational hypertension [30]. Isolated headache and neck pain are non-specific and do not by themselves justify screening, because up to 25% of women in the general population have migraine during their lifetime [2, 30]. The 2024 European hypertension guideline recommends considering FMD as a cause of secondary hypertension in young women and screening for secondary causes in young hypertensive adults [31]. Diagnosis takes, on average, about five years from the first symptoms [30].

Source: tables 1 and 2 of the international consensus [2]. The 2024 European guideline on peripheral arterial diseases lists overlapping signs for renal artery disease in general, adding deterioration of renal function after renin-angiotensin system blockade, hypertensive crisis and flash pulmonary oedema [57]. The French national protocol recommends looking for renal stenosis due to FMD in the same situations (hypertension before 30 years, especially in women; accelerated or malignant; blood pressure of 180/110 mmHg or higher; resistant to triple therapy with a diuretic; small kidney) and adds hypertension in a first-degree relative of a patient with FMD [33]. The same document stresses that asymptomatic lesions are frequent and that the causal relationship between lesion and symptom is not automatic: essential hypertension or cerebrovascular disease of another cause may coexist with FMD [33].

4.2. Contexts that should prompt a search for FMD

SCAD is a strong trigger: all patients with SCAD should undergo brain-to-pelvis imaging, at least once, to look for FMD and other extracoronary anomalies [2]. In known FMD, a Takotsubo syndrome or myocardial infarction with non-obstructive coronary arteries should prompt review of the coronary angiogram to exclude SCAD [30]. In spontaneous renal artery dissection, an underlying vascular disease was identified in about 60% of cases investigated with whole-body imaging, FMD in 26%, with more new dissections during follow-up, so brain-to-pelvis CT angiography is reasonable in young patients, a strategy the authors consider applicable to other dissections [30]. In cervical dissection, FMD coexists in 6–8% of cases and predicts recurrence [29, 49]. In young patients with ischaemic stroke without risk factors, urgent CT angiography from the aortic arch to the intracranial arteries makes it possible to identify dissections and aneurysms and to distinguish FMD from other arteriopathies [30].

4.3. Warning and emergency signs

Emergencies are sudden unilateral neck, facial or head pain with focal signs (cervical dissection), thunderclap headache (subarachnoid haemorrhage), chest pain in a young or postpartum woman (SCAD), sudden lumbar or flank pain with haematuria (renal dissection or infarction), severe abdominal pain with shock (visceral dissection) and acute limb ischaemia; patients should be taught to seek immediate care in the presence of signs of TIA, stroke, CeAD or SCAD [2]. In pregnancy and the postpartum period, a rise in blood pressure, new headache or chest pain require rapid assessment [2, 30].

Some findings should suggest a hereditary arteriopathy rather than idiopathic FMD: a family history of arterial dissections (rare in FMD), easy bruising, thin translucent skin, pneumothorax or bowel rupture (vascular Ehlers-Danlos), bifid uvula, hypertelorism, arachnodactyly, pectus and joint laxity (Loeys-Dietz), café-au-lait spots (neurofibromatosis type 1), facial dysmorphism with supravalvular aortic stenosis (Williams) or brachysyndactyly with bone fragility (Grange) [30, 39]. Multiple or recurrent dissections or ruptures of medium-sized arteries before 40 years should raise the possibility of vascular Ehlers-Danlos [58].

4.4. Children

In children, FMD almost always presents with hypertension (100% in the US registry), often severe, with headache, abdominal bruit, left ventricular hypertrophy, heart failure or growth failure [24, 40]. The triad of severe hypertension, polyuria and polydipsia with hyponatraemia and hypokalaemia (hyponatraemic hypertensive syndrome) should prompt a search for unilateral renal artery stenosis [55]. In children with cerebral arteriopathy, renovascular hypertension may arise years later, which justifies regular follow-up of blood pressure [39]. There is no newborn screening.

5. Diagnosis: Criteria, Tests and Algorithms

5.1. Diagnostic criteria

The diagnosis of FMD is radiological and rests on three conditions: at least one typical focal or multifocal lesion in an arterial bed; exclusion of spasm, standing waves, artefacts, atherosclerosis, vasculitis and monogenic arteriopathies; and classification of the lesion as focal or multifocal [2]. Isolated aneurysm, dissection or tortuosity is insufficient but, when accompanying a typical lesion in another bed, counts as multivessel involvement of all affected beds [2]. There is no validated blood biomarker or specific genetic test [2, 37].

5.2. Imaging when renal FMD is suspected

The international consensus recommends CT angiography as the initial examination, because of its better spatial resolution and the detection of small calcifications that help to distinguish atherosclerotic stenosis, with contrast-enhanced MR angiography as an alternative if CT is contraindicated; duplex Doppler ultrasound as the first examination should be used only in centres with extensive experience in FMD, because the velocity thresholds were extrapolated from atherosclerosis, the examination is operator-dependent and the distal segments and branches, where FMD is frequent, may not be visualised [2, 30]. The 2024 European guideline on peripheral arterial diseases, which deals with renal artery stenosis in general (more than 90% atherosclerotic), recommends duplex Doppler as first line (class I, level B) and MR angiography or CT angiography when Doppler is suspicious or inconclusive (I, B), with criteria such as a peak systolic velocity above 200 cm/s for stenosis above 50% (sensitivity 95%, specificity 90%) [57]. The divergence reflects different populations: in patients with a specific suspicion of FMD, the reference is the 2019 consensus. The 2024 European hypertension guideline accepts duplex Doppler, CT angiography or MRI in the investigation of renovascular hypertension and points out that a very high renin increases suspicion, without high sensitivity [31]. The French protocol, which predates the consensus, proposes a sequential algorithm: duplex Doppler as screening in people at risk of renal artery stenosis (stenosis or renal asymmetry); if positive, confirmation by CT angiography or MR angiography; if negative with high clinical suspicion, another imaging examination; CT angiography and MR angiography are specific for the multifocal appearance, but poorly suited to grading the stenosis [33].

Catheter angiography is the reference standard, but is indicated only when the result may change management: confirmed FMD in a candidate for angioplasty or high suspicion with negative non-invasive imaging [2]. Angiography carries a risk of complications at the puncture site (haematoma, dissection), dissection of the artery studied during selective catheterisation and, like CT angiography, contrast nephrotoxicity; the French protocol likewise reserves it for patients in whom revascularisation is planned in the same session or with high suspicion and persistent doubt [33]. In multifocal FMD, imaging does not allow the haemodynamic significance to be assessed, and measurement of the translesional gradient, ideally with a pressure wire, is recommended before and after angioplasty; a threshold of 10% of mean aortic pressure (Pd/Pa below 0.90) has been proposed, extrapolated from atherosclerosis and not validated in FMD [2]. In a paediatric series, CT angiography, MR angiography and ultrasound were often discordant with angiography, which should be performed when suspicion of renovascular hypertension persists [59]. In the paediatric series of 25 children with renovascular FMD, taking angiography as the reference, sensitivity was 28% for duplex Doppler (38.5% for main trunk lesions), 62.5% for MR angiography and 84.2% for CT angiography (specificity 70%); 28% of the children had lesions beyond the second bifurcation of the renal artery that only angiography showed, which led the authors to recommend angiography in the initial investigation of any child with suspected renovascular FMD [53]. These estimates were obtained only in children with confirmed FMD, in a small sample and without blinded reading, and cannot be generalised to screening [53].

The French protocol devotes a section to the concept of functional stenosis: stenosis that causes ischaemia of the downstream kidney, stimulates the renin-angiotensin system and causes renovascular hypertension that is in principle reversible with revascularisation. Many FMD lesions do not cause it, and only functional stenosis justifies renal revascularisation [33].

Sources: [2, 33].

5.3. Imaging when cerebrovascular FMD and FMD in other beds are suspected

There are no data to favour one modality; CT angiography or contrast-enhanced MR angiography are the initial choices, depending on local resources, and, in the emergency setting (stroke, suspected dissection), CT angiography is preferred because it also assesses the aortic arch and thorax [2, 30]. Carotid duplex Doppler is reasonable in high-volume centres and useful in follow-up, but does not assess the distal internal carotid, the vertebral arteries or the intracranial arteries; there are no validated Doppler criteria for FMD, although turbulence, high velocities and tortuosity in the mid-distal internal carotid are suggestive [2]. Catheter angiography is reserved for treatment planning. For the visceral and limb beds, Doppler may identify stenosis, turbulence and a parvus-tardus waveform, but is less sensitive than CT angiography, MR angiography or angiography [2]. In the rare cases of limb ischaemia due to FMD of a superficial artery, duplex Doppler is the usual first-line imaging; in mesenteric ischaemia, CT angiography or ultrasound [33].

5.4. Systemic assessment after diagnosis

Whatever the initial bed, all patients with FMD should undergo, at least once, imaging of all vessels from brain to pelvis, usually by CT angiography or MR angiography, to detect other lesions and occult aneurysms and dissections; the sequential approach of earlier documents has been abandoned [2]. The recommendation includes a search for intracranial aneurysm by brain CT angiography or MR angiography; it is not known whether this examination should be repeated when negative [2]. The 2024 European hypertension guideline likewise recommends head-to-pelvis CT angiography or MR angiography in renovascular hypertension due to FMD [31]. Coronary imaging is not recommended in the absence of symptoms [2, 30]. In children, the baseline assessment includes blood pressure (with ambulatory monitoring if necessary), echocardiogram and renal duplex Doppler, and digital subtraction angiography is better at diagnosing branch stenoses [39]. The French protocol followed the conditional approach, since abandoned: in renal FMD, look for lesions of the supra-aortic trunks and intracranial lesions only if their discovery would change management; in FMD of the supra-aortic trunks, look for intracranial aneurysm after informing the patient that treatment of unruptured aneurysms is poorly standardised; and, in a hypertensive patient with cervical FMD, look for renal FMD [33].

Sources: [2, 30, 31].

5.5. Renal angiography and angioplasty protocol (2019 consensus)

In focal FMD that is severe on inspection, the prior gradient may be omitted, but measurement after treatment is essential [2].

5.6. Genetic testing: indications, choice and limitations

There are no specific genetic tests for FMD, and the international consensus does not justify testing asymptomatic relatives; the susceptibility loci confer modest increases in risk and have no individual clinical utility [2, 30]. The genotype of rs9349379 or of any other GWAS polymorphism should not be requested or reported as a diagnosis [2, 30]. Genetic testing is indicated when the phenotype suggests a hereditary arteriopathy: a family history of dissections or of sudden death at a young age, multiple dissections or ruptures before 40 years, cutaneous or visceral signs of vascular Ehlers-Danlos, features of Loeys-Dietz, syndromic dysmorphism, arteriopathy of paediatric onset or a phenotype overlapping vEDS and multifocal FMD, a situation in which analysis of COL5A1 should be considered [4, 30]. In unselected patients with cervical dissection, a 38-gene panel identified causal variants in only 1.1% (COL3A1 and ABCC6) and variants of uncertain significance (VUS) in 13.6%; in a review of 14 studies (330 patients), the proportion of carriers ranged from 0.4% in unselected series to 23.4% with a family history of dissection, which supports testing targeted only at patients with a high pre-test probability [60]. In SCAD, variants in vascular connective tissue disease genes (mainly COL3A1) appear in fewer than 5% of patients tested [46].

In a child with arteriopathy, trio exome or genome sequencing is preferred, with reanalysis of negative results, because paediatric intimal fibroplasia is common to several monogenic arteriopathies [39]. An arteriopathy panel including COL3A1, COL5A1, TGFBR1, TGFBR2, SMAD3, TGFB2, ACTA2, MYH11, NF1, ELN (with copy-number analysis for the 7q11.23 deletion), JAG1, NOTCH2, YY1AP1 and ENPP1 covers the main differentials; the inclusion of ENPP1 is justified because a child with a clinical diagnosis of paediatric FMD had ENPP1 deficiency [2, 17, 39, 40]. A negative result does not exclude a hereditary arteriopathy (deep intronic variants, rearrangements, mosaicism, genes not yet described) and does not alter the diagnosis of FMD, which remains clinical and radiological. A variant such as COL5A1 c.1540G>A should be reported with the transcript NM_000093.5, the nomenclature p.(Gly514Ser), the zygosity and the laboratory's ACMG/AMP classification, noting that ClinVar has conflicting classifications, and familial segregation may help to interpret it, bearing in mind incomplete penetrance [3, 45]. VUS in arteriopathy genes should not guide predictive testing in relatives.

5.7. Prenatal and preimplantation diagnosis

In multifactorial FMD there is no indication for prenatal or preimplantation diagnosis. In monogenic forms with a confirmed pathogenic or likely pathogenic variant (for example, vascular Ehlers-Danlos, Loeys-Dietz or Grange syndrome), the reproductive options follow those of these entities; for the COL5A1 p.(Gly514Ser) variant, the conflicting classification and incomplete penetrance limit reproductive use [3, 45].

6. Differential Diagnosis

6.1. Comparative table

The French protocol adds that the multifocal appearance, almost pathognomonic, has been described in poisoning by sympathomimetics and ergot derivatives, exposure to which guides the diagnosis; that the distinction between proximal unifocal FMD and atherosclerotic stenosis rests on age and the absence of risk factors and plaques, and may be difficult in early atheroma; that unifocal renal stenosis may be due to Takayasu arteritis; and that the differential includes rare diseases recognised by family history, syndromic phenotype and gene or chromosomal anomalies [33].

6.2. FMD versus vascular Ehlers-Danlos

This is the differential with the greatest consequences. In vascular Ehlers-Danlos, the diagnosis is often made only after a catastrophic complication or at autopsy; dissections and ruptures affect medium-sized arteries in different territories, synchronously or recurrently, before 40 years, and rupture without a prior aneurysm occurred in 33% of patients with a serious haemorrhagic complication in a literature review [58]. Estimated median survival is 50 years and 70% of adults have a major complication before 30 [61]. Management differs: in vEDS, conventional angiography and arterial manipulation are avoided, antiplatelets and anticoagulants are avoided routinely, and celiprolol reduced vascular events in an open-label randomised trial of 53 patients (a 36% reduction, with an event rate still of 20% in the treated group), whereas in FMD antiplatelet therapy is reasonable and renal angioplasty is the treatment of choice for significant stenoses [2, 58, 61]. The "beaded" appearance may appear in vEDS during healing of a dissection, and the COL5A1 p.(Gly514Ser) variant produces a phenotype reminiscent of vEDS, which makes genetic testing decisive when there are multiple dissections [2, 4].

The clinical criteria for vEDS help in deciding whether to request COL3A1: major criteria are arterial rupture in a young individual, bowel rupture without risk factors, uterine rupture, carotid-cavernous fistula and a family history with a known pathogenic COL3A1 variant; minor criteria include atraumatic bruising at unusual sites, thin translucent skin, characteristic facies, acrogeria, hypermobility of small joints, tendon or muscle ruptures, clubfoot and congenital hip dislocation, early varicose veins, spontaneous pneumothorax, gingival recession and keratoconus [58, 64]. Gastrointestinal rupture occurs in about 25% of patients with vEDS and spontaneous pneumothorax in 12% [58]. Pregnancy also separates the two entities: in vEDS, a large series recorded pregnancy-related death in 5.3% of pregnancies, arterial dissection or rupture in 9.2% and uterine rupture in 2.6%, whereas in FEIRI the arterial complications of pregnancy in FMD were below 1% [30, 58].

6.3. Syndromes with focal renal stenosis in children

Neurofibromatosis type 1, Williams-Beuren syndrome and Alagille syndrome are the most frequent syndromic causes of paediatric focal renal stenosis, with an angiographic appearance indistinguishable from focal FMD and a frequent association with mid-aortic syndrome (blood pressure gradient between upper and lower limbs, weak femoral pulses) [40, 76]. The term "aorto-renal dysplasia" has been proposed to bring together these forms and focal renal FMD of childhood, associated with NF1, JAG1, NOTCH2, ELN, TSC1, TSC2, YY1AP1, PDGFRB and NOTCH3 [40]. Targeted examination (skin, face, liver, spine, calcium) and trio genetic testing help to separate idiopathic FMD from syndromic forms [39].

6.4. Cerebral arteriopathies and moyamoya

In children, the "beaded" appearance is non-specific and intimal fibroplasia is common to several monogenic arteriopathies, which led to the proposal of the term "childhood cerebral and systemic arteriopathies"; up to 15% of patients with moyamoya have extracranial involvement, including hypertension [39]. Smooth muscle dysfunction due to ACTA2 produces fusiform dilatation of the internal carotid arteries and distal stenosis, with periventricular hyperintensities in almost all patients [58]. The first FMD exomes suggested a nominal association with RNF213, the moyamoya disease gene, and the LRP1 allele opposite to the FMD risk allele is associated with moyamoya, but these relationships have no diagnostic application [7, 37].

6.5. SCAD and cervical dissection without FMD

SCAD and CeAD may occur without FMD. In SCAD, rare variants in fibrillar collagens and in Loeys-Dietz syndrome genes are enriched, unlike in severe FMD, and brain-to-pelvis imaging looks simultaneously for FMD, aneurysms and signs of connective tissue disease [2, 37, 47]. In unselected CeAD, the yield of the genetic panel is low (1.1%), and testing should be reserved for patients with a family history or syndromic signs [60].

7. Treatments and Risk Management Strategies

7.1. General principles

There is no therapy targeted at the mechanism of FMD, nor are there randomised trials of medical treatment or comparing medical treatment with intervention; the recommendations rest on registries, series and expert consensus [2, 30]. The aims are to control blood pressure, prevent thrombotic and thromboembolic events, identify and treat aneurysms and dissections, relieve symptoms (headache, tinnitus) and revascularise haemodynamically significant renal stenoses that cause hypertension or renal dysfunction. Follow-up is by professionals experienced in FMD, with coordination between vascular medicine, nephrology, cardiology, neurology, interventional radiology and obstetrics [2, 30].

7.2. Antiplatelet therapy

In the absence of contraindications, antiplatelet therapy with aspirin 75–100 mg/day is considered reasonable by the international consensus to prevent thrombotic and thromboembolic complications, even in asymptomatic FMD, because the webs and dilatations of multifocal lesions may serve as a niche for platelet aggregation [2]. There are no placebo-controlled studies or data favouring one antiplatelet agent, and the decision should weigh the bleeding risk (previous subarachnoid haemorrhage, large intracranial aneurysm, other haemorrhages) and the factors that strengthen the indication (thromboembolic events, dissection, revascularisation) [2]. In the US registry, 72.9% of patients were on antiplatelet therapy, mainly aspirin [2]. The 2026 practical review is more selective: it recommends low-dose aspirin mainly in carotid or vertebral FMD, after TIA or dissection, and in severe multivessel disease [30]. The use of aspirin in FMD rests on expert consensus, without specific trials. In children with arterial ischaemic stroke, secondary prevention uses aspirin 3–5 mg/kg/day or anticoagulation (low-molecular-weight or unfractionated heparin) depending on the aetiology; the source sets no maximum dose and there are no data on optimal duration or on prolonged use in renal or visceral arteriopathies, so applying this dose to paediatric FMD without stroke is an extrapolation [39].

7.3. Treatment of hypertension

The ideal blood pressure target in FMD is unknown, so the general hypertension guidelines are followed (ACC/AHA 2017 and ESC/ESH 2018 at the time of the consensus; the 2024 European recommendations in the 2026 review) [2, 30, 31]. Angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) are often preferred in renal FMD, because they act on the renin-angiotensin-aldosterone system, although activation of this system is inconsistent in multifocal disease; they require monitoring of creatinine and potassium, especially in tight bilateral stenosis or a single functioning kidney, because of the risk of acute kidney injury [30, 31]. Blood pressure control is particularly important in the presence of aneurysms, and beta-blockers, calcium channel blockers and ARBs may also serve as migraine prophylaxis [2]. After SCAD, beta-blockers may have a protective effect against recurrence [2]. Most patients with FMD-associated hypertension respond to medical treatment, which remains first line [30, 31].

7.4. Renal revascularisation: indications and technique

The sources converge on angioplasty without stenting; they differ in the wording of the indications (the ESC peripheral disease guideline requires high-risk features and renal viability, criteria inherited from atherosclerotic stenosis, whereas the consensus and the ESC hypertension guideline focus on hypertension with significant stenosis). Renal stenting is not routinely indicated: kinking and fracture of stents have been described, and in the ARCADIA-POL registry systematic stenting brought no benefit and had stent-related complications in 58%, including in-stent occlusion with recurrence of hypertension or renal deterioration [2, 30]. Surgery remains for complex bifurcation or branch lesions, stenoses with complex aneurysms or failure of angioplasty, and repeated angioplasties should be considered carefully so as not to compromise future surgery [2]. The French protocol asks that revascularisation be proposed by a multidisciplinary team experienced in the disease, for the same reason [33]. The European peripheral disease guideline defines signs of renal viability (kidney longer than 8 cm, cortex thicker than 0.5 cm, albumin/creatinine ratio below 20 mg/mmol, resistive index below 0.8) and haemodynamic criteria (mean resting gradient above 10 mmHg, hyperaemic systolic gradient above 20 mmHg or Pd/Pa of 0.9 or less) [57]. Methods of computational modelling of renal haemodynamics from CT or MR angiography and quantitative analysis of the geometry of the "beads" are under investigation, to estimate the gradient without invasive measurement [30].

7.5. Results of revascularisation

These studies are observational, heterogeneous in their definitions of cure and in period, and do not allow direct comparison between angioplasty and medical treatment or between populations; the difference between Asian and white patients may reflect age and the proportion of men, of focal forms and of selection criteria [79, 80]. In the 2010 meta-analysis, 18% of patients repeated the procedure, and the probability of cure was associated with younger age and shorter duration of hypertension, which reinforces the value of early diagnosis [2, 79]. Adverse events of angioplasty in FMD occur in about 12% of procedures (access complications in 3%, renal complications such as dissection, occlusion, thrombosis, embolisation or rupture in 8%, mortality below 1%), based on older studies [30].

7.6. Care after renal angioplasty

After angioplasty, the consensus indicates aspirin 75–100 mg/day indefinitely; some operators prescribe dual antiplatelet therapy for 4–6 weeks, empirically [2]. Previous antihypertensives can generally be stopped at discharge after successful angioplasty and the need is frequently reassessed during the first year; renal duplex Doppler surveillance is performed at the first visit (usually in the first month), then every six months for 24 months and then annually, or earlier if there is an unexplained rise in blood pressure or decline in renal function [2]. In children, blood pressure may fall abruptly after angioplasty, so antihypertensives are stopped during the procedure and blood pressure is monitored [39].

7.7. Cervical dissection and intracranial aneurysms

Carotid or vertebral dissection in FMD is treated as in the population without FMD: intravenous thrombolysis and mechanical thrombectomy in eligible patients with acute stroke, sometimes with acute carotid stenting; an anticoagulant or antiplatelet agent for at least 3–6 months in patients with stroke or TIA, the AHA/American Stroke Association position supported by the CADISS trial, which the consensus extends to patients with FMD; thereafter, prolonged antiplatelet therapy [2]. The French protocol, which predates CADISS, proposes anticoagulation for a few weeks to a few months in cervical dissection and, outside acute dissection, in patients with FMD and an ischaemic event, an antithrombotic agent, usually antiplatelet, whose efficacy has never been evaluated in this indication; revascularisation of cervical lesions is considered only in symptomatic FMD, by decision of an experienced multidisciplinary team [33]. Data on direct oral anticoagulants are very limited, stenting is reserved for persistent ischaemia despite optimal treatment and dissection pseudoaneurysms rarely require treatment [2]. In the 2026 US cohort, patients were discharged on single antiplatelet therapy (49%), dual antiplatelet therapy (29%) or anticoagulation (22%), with no difference in event rates [49]. Unruptured intracranial aneurysm is managed as in the general population (mean annual risk of rupture below 1%, it being unknown whether FMD increases it), with a decision based on number, size, shape and location, hypertension, smoking and patient preferences; clipping and coil embolisation, with or without stents and flow diverters, do not differ from those used without FMD [2, 21].

7.8. Renal and visceral dissection and aneurysms

Most renal and visceral dissections are treated medically with imaging surveillance; empirical anticoagulation for 3–6 months may be used, especially with distal thromboembolic lesions, followed by prolonged antiplatelet therapy, or antiplatelet therapy from the outset (aspirin alone or with clopidogrel), with no data allowing a consensus point [2]. Intervention (covered stent, coil embolisation, surgery) is justified in the presence of progressive malperfusion, progression of the dissection or secondary aneurysm; recanalisation of an already infarcted territory brings no benefit [2]. For renal and visceral aneurysms, intervention is usually proposed above 2 cm (data extrapolated from patients without FMD); many experts consider a threshold below 2 cm in women of childbearing age who are planning pregnancy, because of the risk of gestational rupture [2]. Symptomatic stenoses of the digestive and lower-limb arteries, which are rare, are treated first line by angioplasty, according to the French protocol [33].

7.9. SCAD associated with FMD

In SCAD, percutaneous coronary intervention has worse results than in atherosclerotic disease, because of the risk of propagating the dissection, and bypass grafts often fail after healing of the native artery; there is therefore a growing consensus in favour of conservative treatment when flow is preserved and there is no ongoing ischaemia [2]. Most dissections heal within 3–6 months, but recurrence was 10.4% in 327 patients followed for a median of 3.1 years; beta-blockade and blood pressure control may reduce recurrence, and the regimen and duration of antiplatelet therapy are uncertain [2]. The details of SCAD management are given in the AHA statement and the ESC study group statement [28, 81].

7.10. Headache, pulsatile tinnitus and drugs to be used with caution

Migraine follows the general recommendations, preferably with follow-up by a headache specialist; triptans, ergotamines (including dihydroergotamine) and other vasoconstrictors should be used with caution and may be contraindicated after CeAD or SCAD [2, 30]. Drugs targeting calcitonin gene-related peptide (CGRP), monoclonal antibodies and gepants, have not been studied in FMD and the trials excluded patients at relevant cardiovascular risk; real-world data recorded cardiovascular events in 3.1% of patients over about 1.5 years, including stroke and coronary dissection, without established causality, while pooled long-term erenumab data showed no increase in ischaemic events, and some experts avoid these drugs in small-vessel disease, distal stenosis or after dissection [30]. For prophylaxis, beta-blockers (propranolol, nadolol, metoprolol) and candesartan have strong evidence in episodic migraine and also serve concomitant hypertension or SCAD [30]. Pulsatile tinnitus often responds to explanation and reassurance, with sound therapy or cognitive behavioural therapy in severe cases and audiological and ear, nose and throat assessment to exclude other causes [2].

7.11. Statins, tobacco, hormones and physical activity

Statins are not routinely indicated, because the disease is not atherosclerotic, and are used when there is a separate indication (dyslipidaemia, coexisting atherosclerosis, chronic kidney disease or overall cardiovascular risk) [2, 30]. Smoking cessation is strongly recommended, because tobacco is associated with earlier symptoms, more renal interventions, more aneurysms and more vascular events [2, 30]. Concerns about oral contraceptives and hormone replacement therapy remain theoretical in FMD [2]; the European hypertension guideline advises against combined oestrogen-progestogen contraceptives in hypertensive women when an alternative exists and considers progestogen-only methods safe [31]. Regular physical activity is encouraged (150–300 minutes per week of moderate aerobic activity and strength training two days a week), with adaptations: after a dissection, postpone intense exertion until healing is documented on imaging and avoid resistance training for about 8–12 weeks; prefer low loads with more repetitions, avoid heavy loads and prolonged Valsalva manoeuvres; avoid contact sports, extreme neck positions, chiropractic or osteopathic neck manipulation and roller coasters [2, 30].

7.12. Pregnancy

Preconception counselling with a professional experienced in FMD and with high-risk obstetrics or maternal-fetal medicine is recommended, especially after CeAD or SCAD or with poorly controlled hypertension; it includes optimisation of blood pressure, assessment of renal stenoses and of cerebral and visceral aneurysms and, in selected cases, preventive renal angioplasty [2, 30]. All aneurysms, regardless of size, should be assessed for the need for prophylactic repair before pregnancy [30]. Pregnancy requires intensive follow-up, blood pressure surveillance in each trimester and in the immediate postpartum period, and an individualised delivery plan (planned caesarean section or assisted second stage) [2]. In FEIRI, 534 pregnancies in 237 women had at least one complication in 40%, gestational hypertension in 25%, preterm delivery in 20%, pre-eclampsia in 7.5% (above the 1.4–4.0% of the general population, but below the 22–26% of chronic essential hypertension), resistant hypertension in 5%, HELLP syndrome in 1%, placental abruption in 1% and fetal death in 4%; arterial complications were below 1% (one cervical dissection 19 days after delivery and one subarachnoid haemorrhage due to aneurysm rupture at 24 weeks) [30]. A British series of 185 pregnancies in 83 women showed gestational hypertension in 22%, pre-eclampsia in 5%, stillbirth in 2% and preterm delivery in 12% [30]. The cohorts included mainly renal FMD, with under-representation of women with cerebrovascular disease or previous dissection; pregnancy should not be systematically discouraged, and postpartum imaging is recommended to assess arterial progression [30]. Antihypertensive therapy should be reviewed before conception according to the general rules for hypertension in pregnancy, which the FMD sources consulted do not detail.

7.13. Children and transition

There are no evidence-based paediatric guidelines; an approach similar to that in adults is used, with blood pressure treated according to paediatric guidelines and particular care because lowering blood pressure may reduce cerebral perfusion when cerebral arteriopathy coexists [39]. Renal angioplasty is reserved for symptomatic stenosis despite optimal medical treatment, or for complications, because of periprocedural morbidity; stenting is avoided in children except for flow-limiting dissection or rupture, and initial medical treatment sometimes allows waiting for growth before intervening [39, 76]. Before surgical revascularisation for moyamoya, extracranial involvement should be sought, and hyperextension or extreme rotation of the neck should be avoided when there is a risk of dissection [39]. Transition to adult care should include brain-to-pelvis imaging, if not yet performed, and discussion of pregnancy and contraception.

7.14. Form associated with COL5A1

Management follows that of FMD with dissections and aneurysms, with attention to the tissue fragility suggested by features of classical Ehlers-Danlos (poor wound healing, postoperative dehiscence) and to the high likelihood of dissection [3, 4]. There are no specific therapeutic data or trials in this form; extrapolation of measures specific to vascular Ehlers-Danlos (celiprolol, restriction of conventional angiography) has not been studied.

7.15. Regulatory status

The sources consulted did not identify orphan medicinal product designations, regulatory applications or therapies targeted at FMD in development; a negative search does not demonstrate non-existence.

7.16. Ongoing studies and developments

Source: ClinicalTrials.gov [82]. There are no trials of targeted drugs or results of randomised trials of antiplatelet therapy or of gradient-guided angioplasty, which the consensus identified as research priorities [2].

In the last 12 months, the developments came exclusively from published literature, without regulatory actions: a practical review by the European and British group with proposals on imaging intervals, exercise, pregnancy and migraine (expert opinion) [30]; a systematic review of cerebrovascular FMD [21]; cohorts of FMD with cervical dissection and of FMD in population-based stroke [49, 56]; data on aortic involvement [50, 51]; meta-analyses of angioplasty by ethnicity and of paediatric FMD [54, 80]; a Polish SCAD registry with silent aneurysms [52]; a genetic panel study in CeAD [60]; and a review proposing a new classification of FMD and discussing imaging and proteomic biomarkers and computational modelling of lesion haemodynamics (expert proposal) [41].

7.17. Divergences between sources

There are three main divergences. First, initial imaging: CT angiography in the 2019 consensus for suspected FMD, duplex Doppler in the European peripheral disease guideline for renal stenosis in general [2, 57]. Second, antiplatelet therapy: reasonable for all in the 2019 consensus, selective (carotid, vertebral, post-dissection, severe multivessel) in the 2026 review [2, 30]. Third, stenting: not indicated except as bail-out in the consensus and the ESC hypertension guideline, provided for as bail-out in the ESC peripheral disease guideline, with no substantive difference [2, 31, 57]. As for relatives, the consensus does not justify assessment of asymptomatic relatives, whereas the 2026 review allows screening of first-degree relatives of patients with particularly severe disease to be considered [2, 30]. The 2010 French national protocol, the only European national guideline dedicated to FMD, diverges from the later sources on five points. In renal imaging, it favours duplex Doppler as screening followed by confirmation by CT angiography or MR angiography, a position close to the European peripheral disease guideline and distinct from the 2019 consensus [2, 33, 57]. In haemodynamic assessment, it considered the transstenotic gradient of as yet undemonstrated value, whereas the consensus recommends it before and after multifocal angioplasty [2, 33]. In the extent of investigation, it allowed the search for cervical and intracranial lesions only when it would change management, whereas the consensus recommends brain-to-pelvis imaging in all [2, 33]. In cervical dissection, it preferred anticoagulation for weeks to months, whereas the consensus, supported by CADISS, accepts an anticoagulant or antiplatelet agent for 3–6 months [2, 33]. In follow-up, it proposed annual cervical and intracranial imaging in asymptomatic forms and reassessment at 3 or 6 months after an ischaemic event, more frequently than the 2–3 years suggested in the 2026 review [30, 33]. The French recommendation to look for renal FMD in a hypertensive first-degree relative is compatible with the consensus, which limits imaging of relatives to those with suggestive signs [2, 33]. The protocol gives no doses and refers only to therapeutic classes (antihypertensives, antithrombotics in cerebral ischaemia, anticoagulants in cervical dissection), so the doses in this section follow the 2019 consensus [2, 33].

8. Reproductive Options and Family Counselling

8.1. Recurrence risk in multifactorial FMD

In most families, FMD behaves as a multifactorial disease, and the risk to relatives should be communicated as empirical and increased relative to the population, without the fixed risks of a Mendelian disease. In the registries, 1.9–7.3% of patients report an affected relative (5.4% in the US registry, 2.8% in the European registry), with 2.4–7.3% familial aggregation according to the 2026 review [2, 30]. In families with vertical transmission, Rushton's analysis and Gladstien's estimate suggested autosomal dominant inheritance with variable and often subclinical expression, and penetrance was estimated at about 0.5 [1, 2]. These figures come from series with clinical diagnosis, without systematic imaging of relatives, and may underestimate subclinical disease and overestimate familial disease through ascertainment bias. The risk polymorphisms (PHACTR1, LRP1, ATP2B1, LIMA1) do not improve the individual estimate and should not be used to counsel relatives [2, 30].

8.2. Assessment of relatives

The international consensus does not justify genetic testing or imaging in asymptomatic relatives; relatives undergo clinical examination and imaging of potentially affected beds only if they have suggestive symptoms or signs (tables 1 and 2) [2]. The 2026 review maintains this position, but proposes selective clinical screening of first-degree relatives with early or resistant hypertension, pulsatile tinnitus, unexplained stroke or dissection in any territory, with targeted imaging, and allows screening of first-degree relatives of patients with particularly severe and disabling disease to be considered [30]. In practice, it is useful to measure the blood pressure of first-degree relatives and to inform them about warning signs (sudden headache, unilateral neck pain, chest pain, pulsatile tinnitus), given the low cost of these measures; this recommendation derives from the consensus signs of suspicion and not from family screening studies. The French protocol recommends asking all patients about early hypertension, dissection, aneurysm or cerebral haemorrhage in first-degree relatives, with the patient responsible for informing relatives of the possibility of familial FMD, and considers it logical to look for renal FMD in a hypertensive first-degree relative [33].

A family history of arterial dissections, sudden death at a young age or multiple aneurysms is rare in FMD and should lead to assessment by medical genetics, because it suggests a hereditary arteriopathy with its own reproductive and cascade risks [30].

8.3. Monogenic forms

In multifocal FMD associated with COL5A1, inheritance is autosomal dominant: each child of a carrier has a 50% probability of inheriting the variant, but arterial penetrance is incomplete, as shown by the carrier relatives without dissection in Richer's family 1 [3]. The conflicting classification of the variant in ClinVar calls for caution in predictive testing and reproductive use; if the laboratory classifies it as pathogenic or likely pathogenic, cascade testing of first-degree relatives allows arterial surveillance to be directed at carriers [45]. In Grange syndrome (autosomal recessive), the risk to siblings of an affected individual is 25%, and in vascular Ehlers-Danlos, Loeys-Dietz and neurofibromatosis type 1 (autosomal dominant) it is 50% for each child of an affected individual, with the prenatal and preimplantation diagnosis options specific to each disease [6, 61].

8.4. Pregnancy as a counselling issue

Reproductive counselling of a woman with FMD concerns mainly the maternal risk: pre-eclampsia in 7.5% and gestational hypertension in 25% of pregnancies in FEIRI, with arterial complications below 1%, and the need to assess aneurysms and stenoses before conception [30]. Transmission to offspring, in the multifactorial form, is a small empirical risk that does not justify prenatal or preimplantation diagnosis.

8.5. Minors

There is no indication to study asymptomatic children of patients with multifactorial FMD, nor to test minors for susceptibility polymorphisms. In monogenic forms with a confirmed pathogenic variant, testing of minors follows the rules of the disease concerned, when the result changes surveillance in childhood (for example, in vascular Ehlers-Danlos); periodic measurement of blood pressure in children of families with FMD is a simple measure consistent with the paediatric signs of suspicion [24, 39].

9. Special Considerations: Population Diversity and Epidemiology

9.1. Prevalence: what each estimate measures

The prevalence of FMD in the general population is unknown, because the disease is often silent and diagnosis depends on imaging performed for other reasons [2, 83]. The available estimates measure different things and should not be confused:

The gap between prevalence on imaging (2.3–4% in donor candidates) and diagnosed prevalence (12 per 100,000) shows that most lesions never reach diagnosis; Orphanet classifies arterial FMD as a non-rare entity in Europe (ORPHA:336), while keeping a code for FMD in the classification of rare circulatory diseases (ORPHA:698012) [14, 15]. SCAD accounts for 10–25% of myocardial infarctions in women under 50 years, and CeAD has an incidence of 2.6 per 100,000 per year [2, 44].

9.2. Sex, age and ancestry

Multifocal FMD affects women in a proportion of about 9:1, with diagnosis between 45 and 55 years; the focal form is more balanced between the sexes and earlier [23, 37]. The registries are dominated by white patients: 91.3% in the US registry (5.0% of African ancestry, 2.6% Hispanic, 0.3% Asian) and 81.8% in the European/International registry (7.2% Asian, 6.6% Hispanic from Argentina, 3.3% from the Maghreb and Middle East), and 88% Caucasian in FEIRI [2, 22]. The genetic studies included only patients of European ancestry, and the frequency of the risk alleles and their applicability in other populations have not been studied [7]. In the angioplasty meta-analysis, Asian patients had more cure of hypertension (40% vs 17%) and fewer complications, and in the paediatric meta-analysis Asian children included fewer girls (43.6% vs 58.1%) and less multifocal FMD (21.8% vs 37.9%) than Caucasian children [54, 80]. Carotid web is the predominant form of cervical lesion in Black and Afro-Caribbean populations [21].

9.3. Founder populations, Portugal and Brazil

The only observation of a founder effect is the shared 160.1 kb haplotype of the COL5A1 p.(Gly514Ser) variant in four probands of Central European ancestry [3]. The sources consulted do not include epidemiological data from Portugal or Brazil; the European/International registry integrates national registries (France, Belgium, Poland) and initiatives in Argentina, Japan, Tunisia and China, and does not document Portuguese or Brazilian centres in the published data [2]. Absence from the sources consulted does not demonstrate the non-existence of published data.

9.4. Special populations

In men, the disease is more focal, earlier and more dissecting; in older people, it coexists with atherosclerosis, which makes the distinction difficult [22]. In pregnancy, the maternal risks are mainly hypertensive [30]. In renal donor candidates, incidental FMD (2.3–4%) raises the question of donor acceptance, for which the sources consulted give no criteria [2, 20]. In children, FMD is a leading cause of renovascular hypertension, with more boys and more focal forms than in adults [24, 54].

9.5. European reference network and patient associations

The relevant European reference network is VASCERN (European Reference Network on Rare Multisystemic Vascular Diseases), whose working groups cover heritable thoracic aortic diseases and medium-sized artery diseases, such as vascular Ehlers-Danlos, which constitute the main differential; FMD, as a non-rare entity, is not listed as a target disease on the pages consulted [32]. The FEIRI registries (based at the Cliniques Universitaires Saint-Luc, Brussels) and the US registry accept patients from participating centres and are the main driver of research [2, 82]. The patient associations include the European Fibromuscular Dysplasia Patient Association (www.fmd-eu.com), the Fibromuscular Dysplasia Society of America (www.fmdsa.org), the FMD Society of UK & Ireland, the FMD Groep Nederland (www.fmdgroep.nl) and Fibromuscular Dysplasia Australasia Advocacy [30, 84, 85].

In France, symptomatic FMD in adults is managed by the reference centre for rare vascular diseases at the Hôpital Européen Georges-Pompidou (Paris) and by regional competence centres (eleven in the 2010 protocol: Marseille, Caen, Toulouse, Montpellier, Tours, Grenoble, Nancy, Lille, Clermont-Ferrand, Lyon and Limoges), and is recognised as an off-list long-term condition, with exemption from patient co-payment through a care protocol between the attending physician and the health insurance medical adviser [33]. The associated list of procedures and services includes consultations in radiology, cardiology, angiology, neurology, internal medicine, nephrology, general practice (in coordination with the centre), vascular surgery, urology, pathology (after surgery), nuclear medicine (before nephrectomy or to assess intracranial haemodynamic impact) and anaesthesia; creatinine with estimated GFR, full blood count with platelets and PT/aPTT at diagnosis and during follow-up; electrocardiogram, renal ultrasound, arterial duplex Doppler, CT angiography, MR angiography and brain MRI; and, as treatments, antihypertensives, antithrombotics in cerebral ischaemia and anticoagulants in cervical dissection [33]. The hospital social worker supports administrative procedures, and the document refers to Orphanet, to the Maladies Rares Info Services helpline and to the US patient association [33].

10. Illustrative Clinical Case

10.1. Presentation

A previously healthy 9-year-old girl was admitted to a Polish paediatric department with acute abdominal pain, preceded for about ten days by polydipsia, polyuria, nocturia, anorexia, progressive weakness, reduced muscle strength and weight loss [55]. The family history was negative for renal and endocrine disease and hypertension. Laboratory tests showed hypokalaemia, hyponatraemia, proteinuria and haematuria with dysmorphic red cells, a fractional sodium excretion of 1.3% and normal renal function (estimated glomerular filtration rate of 101 mL/min/1.73 m²) [55]. Blood pressure remained high, averaging 150/110 mmHg, with a maximum of 166/124 mmHg, measured by validated oscillometry and confirmed by auscultation; the cortisol profile, adrenocorticotropic hormone and plasma metanephrines were normal [55].

10.2. Investigation

Ultrasound, initially reported as normal, revealed in the paediatric nephrology unit a marked asymmetry (right kidney 65 mm and left 92 mm) and Doppler showed low-resistance flow in the right intrarenal arteries; scintigraphy confirmed reduced perfusion and slow excretion on the right [55]. CT angiography demonstrated a severe focal stenosis of the right renal artery, about 1.5 mm in diameter over 6 mm, close to the aortic origin, with a normal left artery and a single artery to each kidney; assessment of the aorta, iliac arteries, coeliac trunk, carotid, vertebral and subclavian arteries and cranial CT showed no other lesions [55]. The fundus showed hypertensive changes and the echocardiogram showed no ventricular hypertrophy. Arteriography confirmed the narrowing close to the origin of the right renal artery, followed by a segment of normal calibre (figure 4 of the article, consulted at https://pmc.ncbi.nlm.nih.gov/articles/PMC13712050/figure/f4-amjcaserep-27-e952551/) [55]. The authors excluded an inflammatory cause and considered FMD the most likely aetiology, in a picture of hyponatraemic hypertensive syndrome due to unilateral renal artery stenosis [55]. No genetic testing was described.

10.3. Treatment and course

Blood pressure and potassium were initially controlled with amlodipine, doxazosin and metoprolol and oral potassium supplementation [55]. On the ninth day, angioplasty of the right renal artery was performed in three stages, with 2 × 20, 3 × 20 and 4 × 20 mm balloons, with good morphological and haemodynamic dilatation; blood pressure normalised and antihypertensives were stopped by day 15, with low-molecular-weight heparin during the procedure and aspirin for six months [55]. At discharge, the laboratory abnormalities had resolved and Doppler showed no restenosis. At 18 months, the patient remained normotensive without medication (110/64 mmHg in clinic; 24-hour mean of 110/68 mmHg on ambulatory monitoring), with kidneys of 88 and 92 mm, no restenosis and normal renin and aldosterone [55].

10.4. Contrast with the second case in the same series

A 4-year-old girl, referred for a heart murmur, had left ventricular hypertrophy, blood pressure up to 200/140 mmHg, raised renin and aldosterone, a right kidney of 62 mm (left 76 mm) and a tardus-parvus pattern on Doppler [55]. Angiography showed a thread-like stenosis greater than 95% close to the hilum, with post-stenotic dilatation and collaterals (figure 3, consulted at https://pmc.ncbi.nlm.nih.gov/articles/PMC13712050/figure/f3-amjcaserep-27-e952551/); the patient developed hyponatraemic hypertensive syndrome with polyuria of up to 5 L per day, attempted angioplasty encountered complete occlusion and right nephrectomy was performed, with resolution of the hypertension and electrolyte abnormalities; at 7 years of age she was normotensive without medication [55].

10.5. Lessons from the case

The case illustrates focal paediatric FMD with renal presentation, the form in which angioplasty is most likely to cure, in keeping with the association between focal lesion, young age and cure of hypertension described in the series and meta-analyses [23, 79, 80]. Assessment of the whole arterial tree, performed in this case by CT angiography, follows the consensus recommendation for systemic imaging, which the 2026 paediatric meta-analysis also considers applicable to children [2, 54]. The second case shows that, in rapidly progressive critical stenosis, functional loss of the kidney may make nephrectomy the definitive solution. Dilatation in three stages with increasing balloons approximates the principle of the adult consensus protocol (progressive balloon increments), but the consensus does not cover the paediatric age group and the report does not describe gradient measurement; the use of periprocedural heparin and of aspirin for six months is the centre's practice and not a guideline recommendation [2, 55]. In a case such as this, genetic testing is justified if there are syndromic signs or a family history, and measuring blood pressure in relatives is a simple measure; neither was described in the report.

11. Prognosis and Long-Term Follow-up

11.1. Prognosis

FMD is a chronic disease whose prognosis depends on the distribution and type of lesions, the presence of aneurysms and dissections and blood pressure control. In the US registry, 41.7% of 921 patients had an aneurysm and/or dissection at the time of diagnosis and 19.2% of the first 447 patients had had a TIA or stroke; in the US and European/International registries, 36.6% and 55.5% of patients underwent at least one vascular procedure [2, 26, 34]. In renal FMD, cure of hypertension after angioplasty ranges from 17% to 54% depending on the population, age and lesion type, and restenosis is around 20% [23, 79, 80]. Progression of renal artery stenosis is slow and rarely leads to ischaemic renal failure, but the disease may progress to tighter stenoses, downstream complications (renal atrophy or infarction, cerebral ischaemia) or new lesions in the contralateral territory or in other beds [33]. In cerebrovascular disease, recurrence of cervical dissection is greater when FMD is present (HR 3.40 in the Italian cohort; 13% over about five years in the US cohort, with cardiovascular events in 28%) [29, 49]. In a population-based stroke study, recurrence of stroke/TIA at five years was 22.9% in patients with cerebrovascular FMD, with no significant adjusted difference compared with patients without FMD, in an elderly population [56]. After SCAD, recurrence was 10.4% over 3.1 years, but primary extracoronary vascular events were rare in a British series followed for five years [2, 25]. Arterial complications in pregnancy were below 1% in FEIRI [30]. There are no population survival data or studies that rigorously separate the natural history from treated disease; patients with FMD associated with COL5A1 appear to have a greater propensity for dissections [4].

11.2. Organisation of follow-up

The consensus recommends at least annual follow-up by a professional experienced in FMD, more frequent in severe disease, with assessment of interim vascular events, migraine, neck pain, pulsatile tinnitus, claudication and mesenteric angina, blood pressure measurement, vascular examination (pulses and bruits), checking of adherence and adverse effects of antiplatelet and antihypertensive drugs, and education about the signs of TIA, stroke, CeAD and SCAD [2]. In renal FMD, renal function and electrolytes should be assessed at least annually, with periodic testing for albuminuria when other risk factors are present [2]. There is no validated follow-up imaging algorithm; the modality and frequency should be individualised according to symptoms, the beds involved, the severity of the lesions, the presence and size of aneurysms, previous revascularisation and local resources [2]. The 2026 review suggests imaging of already affected beds every 2–3 years, alternating duplex Doppler or MR angiography with CT angiography, extendable to 5 years when lesions are mild and stable, without systematic reimaging of normal beds in the absence of new symptoms [30].

In revascularised patients, imaging surveillance is more frequent in the first two years [2]. The French protocol assesses the efficacy of revascularisation by comparing blood pressure, antihypertensive medication and GFR before and after the intervention, and makes follow-up after subarachnoid haemorrhage depend on the initial treatment of the aneurysm; its cervical imaging intervals are shorter than those of the 2026 review [30, 33].

12. Summary and Final Considerations

Fibromuscular dysplasia is a non-atherosclerotic, non-inflammatory arteriopathy of medium-sized and small arteries, diagnosed by imaging of a focal or multifocal lesion after other arteriopathies have been excluded. It mainly affects middle-aged women, frequently involves several beds (renal, carotid, vertebral, visceral, peripheral and, more rarely, aortic) and is associated with hypertension, headache, pulsatile tinnitus, stroke, aneurysms and dissections, including cervical dissection and spontaneous coronary artery dissection. The prevalence on imaging in populations without symptoms is around 2–4% for the renal arteries, far above the diagnosed prevalence.

The genetic component is mainly polygenic: SNP-based heritability is around 0.43, and five loci (PHACTR1, LRP1, ATP2B1, LIMA1 and SLC24A3) point to arterial contraction and calcium homeostasis, with genetic overlap with blood pressure, migraine, intracranial aneurysm and cervical dissection and opposition to atherosclerotic coronary artery disease. The PHACTR1 polymorphism rs9349379, which regulates endothelin-1 through an arterial enhancer, illustrates this pleiotropy, but has no individual diagnostic value. Familial aggregation exists in a minority of patients (1.9–7.3%), with transmission compatible with dominant inheritance with incomplete penetrance in some families. Monogenic forms are rare: multifocal FMD associated with COL5A1 p.(Gly514Ser), with dissections and features of classical Ehlers-Danlos, and the enrichment of PTGIR loss of function; Grange syndrome, vascular Ehlers-Danlos, Loeys-Dietz, neurofibromatosis type 1, Williams-Beuren syndrome and Alagille syndrome produce similar lesions and are differential diagnoses with their own therapeutic and familial consequences.

The current approach rests on the 2019 international consensus and the 2024 European guidelines: CT angiography or MR angiography of the suspected territory and, after diagnosis, one-time brain-to-pelvis imaging; antiplatelet therapy with low-dose aspirin in most patients; blood pressure control according to the general guidelines, with a preference for ACE inhibitors or ARBs in renal disease; smoking cessation; balloon angioplasty without stenting for haemodynamically significant renal stenoses, with a greater likelihood of cure in young patients and focal lesions; management of dissections and aneurysms as in the general population; and at least annual follow-up, with individualised imaging. Genetic testing is not routinely indicated, nor in asymptomatic relatives, but should be requested when the phenotype, age or family history suggests a hereditary arteriopathy. Pregnancy is generally possible with specialist follow-up. Trials of antiplatelet therapy and of gradient-guided angioplasty, longitudinal natural history studies and data from non-European populations, Portugal and Brazil are lacking.

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