Patau Syndrome (Trisomy 13)

Literature and regulatory information updated: 4 October 2026.

Patau Syndrome (Chromosome 13 Trisomy) — Medical Genetics Lecture, specialist/clinical geneticist level

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0. Initial Reference Table

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1. Introduction

The earliest clinical description attributed to chromosome 13 trisomy dates to the Danish anatomist Thomas Bartholin, who in 1657 reported a newborn with multiple congenital abnormalities retrospectively consistent with the syndrome. This accounts for the historical name Bartholin–Patau syndrome, still found in older European publications [5,7]. For three centuries, however, the condition lacked a systematic nosological identity and appeared in scattered descriptions of multiple malformations without an established cause.

The decisive advance came in 1960, when Klaus Patau and colleagues, including David W. Smith, Eeva Therman, Stanley L. Inhorn and Henry P. Wagner, published the foundational Lancet article “Multiple congenital anomaly caused by an extra chromosome”. They demonstrated for the first time that an infant with the characteristic dysmorphic phenotype had 47 chromosomes because of an additional group D chromosome, subsequently identified as chromosome 13 [5]. This finding emerged at a pivotal stage in human cytogenetics, only one year after Lejeune, Gautier and Turpin demonstrated chromosome 21 trisomy in Down syndrome (1959), establishing that complete autosomal aneuploidies could be compatible with life despite severe malformation phenotypes.

Warburg and Mikkelsen (1963) subsequently reinforced the genotype–phenotype association with another case described as “trisomy 13–15”, terminology reflecting the difficulty of distinguishing group D acrocentric chromosomes before chromosome banding became available [5,19]. Smith, a coauthor of the original article, published a systematic review of known autosomal abnormalities in 1964, consolidating clinical recognition criteria later incorporated into reference works such as Smith's Recognizable Patterns of Human Malformation. This principal source quantitatively summarises individual findings from decades of accumulated cases [7,20]. Warkany, Passarge and Smith (1966) extended this phenotypic characterisation through systematic comparison of the recognised autosomal trisomy syndromes (13, 18 and 21) [7,21].

Trisomy 13 is now recognised as the third most frequent autosomal aneuploidy among live births, after trisomies 21 and 18. Together they constitute the “major trisomies” routinely screened in contemporary obstetric practice using non-invasive prenatal testing (NIPT) [14,15]. The Brazilian reference also identifies the condition as a leading cause of miscarriage in early pregnancy, notes greater frequency in pregnancies above maternal age 35, and reports a female predominance [4]. Its academic relevance extends beyond description: Patau syndrome provides a model for studying gene dosage effects on cephalic midline morphogenesis and has historically informed understanding of the holoprosencephaly spectrum, now recognised as the most common structural abnormality of the human forebrain [22].

The molecular, clinical, diagnostic and therapeutic evidence integrates the classical cases of Patau and colleagues with more recent epidemiological data, surgical outcomes and professional guidance. These include the American Association for Thoracic Surgery (AATS) 2023 consensus document [16] and the American Academy of Pediatrics (AAP) 2025 clinical report [17], which substantially revised the ethical framework for treating affected children.

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2. Molecular Genetics and Pathophysiology

2.1 Cytogenetic basis

Approximately 75–80% of Patau syndrome cases result from free, complete chromosome 13 trisomy (47,XX,+13 or 47,XY,+13), arising through meiotic nondisjunction. The origin is maternal in approximately 90%, with similar proportions of maternal meiosis I and meiosis II errors in the largest published molecular series (82 conceptuses) [23]. No primary gene mutation is identifiable in these cases; pathogenicity reflects chromosomal dosage alone [1,2]. Approximately 20% result from an unbalanced Robertsonian translocation, in which the long arm of the additional chromosome 13 is fused to another group D or G acrocentric chromosome, most commonly chromosome 14, producing der(13;14). The translocation may arise de novo or be inherited from a parent carrying a balanced Robertsonian translocation, a distinction with direct consequences for recurrence risk [2,6,24]. The remaining 5% have trisomy 13 mosaicism following postzygotic mitotic nondisjunction, producing euploid and trisomic cell lines whose relative proportions substantially influence phenotypic severity and survival [2,25].

Oxford Desk Reference gives a different distribution: 90% free trisomy 13, 5–10% translocation, usually an unbalanced 13;14 Robertsonian translocation, and a small mosaic proportion. It states that approximately 90% of trisomy 13 conceptions arise from maternal meiosis I nondisjunction and that most end in miscarriage [3]. Bugge et al.'s molecular analysis (2007), using 21 microsatellites in 82 conceptuses, confirmed maternal origin in 89% but found nearly equal numbers of maternal meiosis I and II errors. This is unusual among human autosomal trisomies, where maternal meiosis I errors predominate in trisomies 15, 16, 21 and 22, and meiosis II errors in trisomy 18. Of nine paternal-origin cases, five resulted from meiosis II errors and none from meiosis I errors [23]. The Brazilian source summarises the three constitutions as follows [4].

Advanced maternal age is the principal population risk factor for free trisomy 13, reflecting age-related oocyte meiotic nondisjunction, analogous to but quantitatively less marked than in trisomy 21 [7]. Even at maternal age 40, the absolute risk of a live birth with trisomy 13 remains approximately 1/2,000 [3]. Trisomies 13 and 21 arising from a parental Robertsonian translocation are not associated with advanced maternal age: the mechanism is abnormal meiotic segregation of a structurally rearranged karyotype rather than age-related nondisjunction [26].

2.2 Pathophysiological mechanism of abnormal morphogenesis

The central mechanism emphasised in the classical reference is an early disturbance, around the third week of embryonic development, of the prechordal mesoderm, which governs midfacial morphogenesis and induces subsequent forebrain development [7]. Disruption of this mesodermal field explains the apparently heterogeneous but mechanistically related facial midline defects (hypotelorism, median cleft lip and palate, absent philtrum) and holoprosencephaly spectrum. The latter ranges from cyclopia (complete orbital fusion with a proboscis) to milder forms such as cebocephaly (a single nose with a central nostril and closely spaced but separate orbits) and less severe lobar forms [7,22].

The chromosome 13 gene most firmly implicated in holoprosencephaly is ZIC2, at 13q32.3 [5,22]. It encodes a zinc-finger transcription factor homologous to the Drosophila odd-paired gene, essential for neurulation and dorsoventral asymmetry of the anterior neural tube. Heterozygous loss-of-function mutations cause holoprosencephaly type 5 (HPE5) through haploinsufficiency [5]. The relationship between ZIC2 triplication in complete trisomy 13, which includes 13q32, and holoprosencephaly is less mechanistically established than the haploinsufficiency relationship. Isolated 13q32 duplications without complete trisomy suggest that increased ZIC2 dosage alone may be relatively well tolerated in some settings. Simultaneous triplication of dozens of other chromosome 13 loci interacting with ZIC2 is considered the most likely determinant of holoprosencephaly in almost three quarters of complete trisomy 13 cases [5,6]. Reported frequencies differ: 60–70% in Oxford Desk Reference [3] and 29% in the Brazilian source [4].

This field defect simultaneously affects ocular, nasal, labial and forebrain structures and was historically termed arhinencephaly or holoprosencephaly, terminology retained in classical references [7]. Phenotypic variation, from cyclopia to minimal manifestations such as hypotelorism and a single central incisor, probably reflects the intensity and precise timing of disrupted mesodermal induction rather than primary aetiological heterogeneity.

2.3 Genotype–phenotype relationships in partial trisomy

Partial chromosome 13 trisomies, already described in the foundational literature, demonstrate a phenotypic distinction relevant to genetic counselling [7]. Proximal partial trisomy (13pter→q14) produces a non-specific pattern of prominent nose, short upper lip, retrognathia and fifth-finger clinodactyly, with severe intellectual disability in most cases but no significant reduction in survival. Genes most relevant to early lethality, particularly major cardiac and cerebral morphogenesis, appear to lie more distally; the overall phenotype resembles complete trisomy 13 only weakly [7]. Distal partial trisomy (13q14→qter), including the ZIC2 critical region at 13q32, produces a more characteristic and severe phenotype: frontal capillary haemangiomas, a short upturned nose, long philtrum, synophrys, thick eyebrows, long curved eyelashes and a prominent antihelix. Severe intellectual disability accompanies an estimated early mortality of approximately 25%; trigonocephaly and arhinencephaly have occasionally been reported [7]. Similarly, the Brazilian source states that partial translocations involving the short arm (p) generally have attenuated symptoms and a more favourable prognosis, whereas those involving the long arm (q) resemble complete trisomy and reduce life expectancy [4].

2.4 Mosaicism and translocation in genetic counselling

Trisomy 13 mosaicism spans a continuous spectrum from a phenotype closely resembling complete trisomy to an almost normal phenotype; survival generally exceeds that of complete non-mosaic trisomy [2,7,25]. Intellectual disability also varies and correlates imperfectly with the proportion of trisomic cells in sampled tissues. This limitation must be explained in prenatal and postnatal counselling, because peripheral lymphocyte proportions may not faithfully represent other tissues, particularly the central nervous system [2,25]. Hsu and Hou (2007), however, demonstrated that mosaicism does not fully explain variable expressivity in Patau syndrome [3].

2.5 Homologous Robertsonian translocations and uniparental disomy

At least 50% of Robertsonian translocations between homologues, such as rob(13q13q), show uniparental disomy (UPD); when the translocation is an isochromosome, UPD risk is 100% [12]. Chromosomes 13, 21 and 22 appear to lack imprinted elements, so chromosome 13 UPD would have a phenotypic effect only in the unlikely event that the parent carries a recessive variant at a chromosome 13 locus unmasked by UPD. Translocations involving chromosomes 14 or 15, such as rob(13;14), require consideration of UPD14 risk (see section 8) [12].

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3. Clinical Spectrum and Manifestations by System

The classical phenotype, established by Patau and colleagues and refined through decades of cases, distinguishes findings affecting at least 50% of patients from those affecting fewer than half, a useful distinction when assessing diagnostic suspicion [7]. The following system-based table presents this stratification alongside more recent European population-series prevalence data [8].

Note: the original Smith's text lists prenatal-onset growth deficiency (mean birthweight 2,480 g) among findings present in fewer than 50% of patients [7].

3.1 Frequencies compared across reference works

The local references report frequencies partly overlapping those in Smith's, with differences reflecting their underlying case series. The following table brings together quantified or listed findings in Oxford Desk Reference [3] and the Brazilian source [4].

ASD, atrial septal defect; VSD, ventricular septal defect.

Neutrophil nuclear projections and persistent fetal haemoglobin have limited prominence in contemporary practice because they are absent from modern diagnostic algorithms, largely superseded by molecular cytogenetics. Nevertheless, they have remained characteristic haematological markers since the original series and may offer additional clues where resources are limited [7].

Patau syndrome epilepsy warrants specific attention: dedicated EEG studies document epileptic spasms and early photosensitivity, often before six months, with an electroencephalographic (EEG) pattern resembling classical West syndrome hypsarrhythmia but with neurophysiological features distinguishing the two conditions [29].

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4. Clinical Recognition and Warning Signs

Clinical recognition classically rests on three cardinal findings widely cited in contemporary literature: orofacial defects (cleft lip and/or palate, often midline), microphthalmia or anophthalmia, and postaxial polydactyly [4,30,31]. Their combination in a newborn should immediately raise suspicion of trisomy 13 and prompt urgent chromosome analysis.

Additional neonatal warning signs include microcephaly with a sloping forehead and wide sutures, posterior occipital aplasia cutis congenita (a circumscribed scalp defect sometimes initially mistaken for birth trauma), narrow hyperconvex nails, a distinctive and readily observed bedside finding, and frontal capillary haemangiomas [7]. Scrotalisation of the phallus and cryptorchidism are also frequent male genital warning signs [7].

4.1 Structured clinical assessment

Oxford Desk Reference organises assessment around the pedigree (a brief history suffices if trisomy 13 is already karyotypically confirmed), maternal age and pregnancy history; examination includes growth measurements and dysmorphic features (cleft lip/palate, microphthalmia, postaxial polydactyly), supported by clinical photographs whenever possible [3].

4.2 Postaxial polydactyly as the presenting finding

Postaxial polydactyly (PAP) is an extra digit on the postaxial, ulnar or fibular side of the hand or foot. Type A is a well-formed digit articulating with a metacarpal; type B is a pedunculated digit, sometimes only a skin appendage, attached to the medial border of the fifth digit [18]. PAP occurs in 1/1,000 to 1/2,000 newborns, and trisomy 13 is its most common chromosomal cause [18]. In a newborn with polydactyly, maternal age, microphthalmia, scalp defects/aplasia cutis, cleft lip and/or palate, and cardiac defects suggest trisomy 13. Recommended investigations include chromosome analysis for trisomy 13, 22q11 deletion and other abnormalities, photographs and radiographs, brain imaging (initially cranial ultrasound in the neonatal period if appropriate), renal ultrasound and echocardiography when indicated [18].

4.3 Prenatal recognition

Obstetric ultrasound is the principal prenatal morphological screening tool, with the most sensitive window for detecting Patau-associated abnormalities after 17 weeks' gestation [31]. Common markers include holoprosencephaly, polydactyly, intrauterine growth restriction, major congenital heart disease and renal abnormalities, particularly hyperechogenic polycystic kidneys [6,31,32]; the Brazilian source adds increased nuchal translucency and small orbits [4]. Because structural malformations are frequent, the anomaly scan detects approximately 90% of trisomy 13 at 20 weeks [3,12]. Holoprosencephaly with polydactyly on a second-trimester scan warrants urgent genetic counselling and an offer of invasive diagnostic testing. This pattern is not pathognomonic and requires differentiation from pseudotrisomy 13 syndrome (see section 6) [33].

An increasing proportion of cases are recognised through prenatal cell-free DNA screening (cfDNA; NIPT) rather than the classical postnatal phenotype. Screening often precedes visible clinical abnormalities and redirects care towards early prenatal counselling [14,15].

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5. Diagnosis: Criteria, Tests and Algorithms

5.1 Prenatal diagnosis

Trisomy 13 screening forms part of the standard panel for the three major autosomal trisomies (13, 18 and 21). Fetal cell-free DNA-based non-invasive prenatal testing (cfDNA/NIPT) is the preferred screening method by unanimous consensus of the American College of Obstetricians and Gynecologists (ACOG), Society for Maternal-Fetal Medicine (SMFM), American College of Medical Genetics and Genomics (ACMG) and International Society for Prenatal Diagnosis (ISPD), and should be offered irrespective of maternal age or baseline risk [14,15]. A large-scale systematic validation review reports approximately 100% sensitivity and 99.9% specificity for trisomy 13 in singleton pregnancies [15,34]. Large clinical series show similar performance: 100% sensitivity (95% CI: 87.5–100%) and 99.99% specificity in an Italian cohort exceeding 36,000 pregnancies [35], and 100% sensitivity with 99.9% specificity in an independent cohort exceeding 7,000 pregnancies [36]. Diagnostic confirmation rates (positive predictive value) after high-risk trisomy 13 cfDNA results are lower than for trisomy 21 because of lower baseline prevalence. A 2021 series reported approximately 84% confirmation [35], reinforcing the requirement for diagnostic confirmation before irreversible clinical decisions.

In a 2023 guideline based on a systematic evidence review published in 2022, the ACMG formally recommended that cfDNA be strongly preferred over traditional screening methods (first-trimester combined screening, second-trimester serum screening) for all pregnant women with singleton or twin pregnancies, with regard to trisomies 21, 18 and 13 [34,37]. However, cfDNA remains a screening test, not a diagnostic one: every high-risk result requires confirmation by an invasive diagnostic test — amniocentesis or chorionic villus sampling, followed by conventional karyotyping — before any definitive clinical decision [15].

Combined and biochemical screening: historical and resource-limited settings. Spencer and Nicolaides (2002) developed a first-trimester trisomy 13/18 risk algorithm combining nuchal translucency thickness, maternal serum free β-hCG (human chorionic gonadotropin) and PAPP-A (pregnancy-associated plasma protein-A). It identifies 95% of these chromosomal abnormalities at 11–14 weeks with a 0.3% false-positive rate [3]. The Brazilian source describes the following screening components [4]:

Invasive diagnosis and strategy in low-risk pregnancies. Prenatal diagnosis is possible through chorionic villus sampling at 11 weeks or amniocentesis at 16 weeks [3]. Given low occurrence and recurrence risks, some women choose detailed anomaly ultrasound instead of invasive diagnosis, proceeding invasively only if an abnormality is suspected. For a woman with a 1% prior risk, a normal anomaly scan reduces risk to below 0.5%, possibly 0.2% assuming an 80% ultrasound detection rate [3]. NIPT should be offered where available [3].

5.2 Confirmatory cytogenetic diagnosis

Conventional G-banded karyotyping remains the reference test for trisomy 13 confirmation, particularly with strong clinical or ultrasound suspicion of a common trisomy. It detects numerical aneuploidy while distinguishing free trisomy from an unbalanced Robertsonian translocation, directly informing familial recurrence risk [6,39]. Fluorescence in situ hybridisation (FISH) using chromosome 13-specific probes provides preliminary results in 24–48 hours, useful in urgent care, but must be supplemented with a complete karyotype [30]. The Brazilian source gives prenatal turnaround times of 14 days for FISH and 30 days for karyotyping, reflecting routine laboratory pathways rather than the methods' technical speed [4].

Chromosomal microarray analysis (CMA) is currently recommended by ACOG and SMFM as the first-line test in cases of fetal structural abnormality identified on ultrasound, in stillbirth, or as a reflex test after an abnormal screening result [39,40]. CMA has a technical limitation: because it relies on detecting a quantitative imbalance in genomic dosage, this method cannot distinguish free trisomy 13 from trisomy 13 due to an unbalanced Robertsonian translocation, since both result in the same gain of genomic material [39]. In these circumstances, conventional karyotyping remains indispensable for complete mechanistic characterisation, with a direct impact on subsequent reproductive counselling [6,39].

5.3 Postnatal diagnosis

Neonatal confirmation follows the same algorithm: G-banded karyotyping as the definitive test, supplemented by FISH when rapid results are needed for immediate decisions [30]. Oxford Desk Reference specifies that the complete fetal/infant karyotype is the key investigation and parental chromosome testing is unnecessary for simple free trisomy 13 [3]. A suggestive newborn phenotype with a normal karyotype requires active consideration of pseudotrisomy 13 (holoprosencephaly–polydactyly, OMIM 264480), an autosomal recessive entity without a chromosomal basis, particularly in parental consanguinity (section 6) [33,41].

5.4 Multisystem assessment after diagnosis

Following cytogenetic confirmation, StatPearls, Orphanet and the AAP 2025 report consistently recommend echocardiography, given the 57–80% congenital heart disease prevalence; renal and abdominal ultrasound; neuroimaging, preferably brain MRI when feasible to characterise holoprosencephaly (Oxford Desk Reference specifies cranial ultrasound initially [3]); ophthalmological and audiological assessment; and parental chromosome studies when the proband has a Robertsonian translocation and this is relevant to the family [1,6,17].

5.5 Test limitations and reporting requirements

Maternal plasma cfDNA originates predominantly from the placenta, so confined placental mosaicism can produce false-positive or false-negative results. Trisomy 13 positive predictive value is lower than for trisomy 21; low-risk screening does not exclude disease when suggestive ultrasound abnormalities such as holoprosencephaly or polydactyly warrant invasive diagnosis regardless of screening [34,35,37]. G-banded karyotyping is the only routine method distinguishing free trisomy, Robertsonian translocation and mosaicism while identifying balanced parental translocations. Its resolution is several million base pairs, and mosaicism detection depends on cell count: 20 metaphases exclude mosaicism of 14% or above with 95% confidence, but not lower levels [42]. If mosaicism is suspected despite a normal blood karyotype, counting additional cells or testing fibroblasts or buccal tissue increases sensitivity; one tissue's proportion does not predict that of the central nervous system [2,25]. QF-PCR and interphase FISH provide rapid results restricted to tested chromosomes. CMA delineates partial gains (13pter→q14 or 13q14→qter) but misses balanced rearrangements, cannot distinguish free from Robertsonian trisomy, and may miss low-level mosaicism [39].

Reports should specify the tissue, counted cells and ISCN 2024 formula, for example 47,XX,+13 for free trisomy, 46,XY,der(13;14)(q10;q10),+13 for Robertsonian trisomy, and mos 47,XX,+13[n]/46,XX[n] for mosaicism. Microarray reports should state the genome assembly, such as GRCh38, and coordinates of the gained segment [43]. Partial trisomies and smaller copy number variants are classified into five categories under ACMG/ClinGen constitutional copy number standards [44]. HGVS nomenclature and MANE transcripts do not apply to whole-chromosome aneuploidy; they apply to monogenic differentials such as non-chromosomal holoprosencephaly due to ZIC2 variants (13q32.3; MANE Select NM_007129.5, confirmed in NCBI in October 2026), Smith–Lemli–Opitz syndrome (DHCR7) or ciliopathies. Such reports should specify the gene, versioned transcript, HGVS notation, zygosity, ACMG/AMP classification and test limitations. Negative exome or genome results do not exclude clinical pseudotrisomy 13, whose molecular basis remains unresolved. A variant of uncertain significance does not become pathogenic through phenotypic compatibility or partial segregation; parental testing investigates its origin, and reclassification requires formal criteria [44].

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6. Differential Diagnosis

The principal differential diagnoses are distinguished by aetiological mechanism and discriminating clinical features [4,6,18,33].

Distinguishing complete trisomy 13 from pseudotrisomy 13 is particularly important because clinically overlapping conditions have fundamentally different inheritance: sporadic de novo aneuploidy versus autosomal recessive disease with 25% recurrence. Chromosome analysis is mandatory even with an apparently unequivocal phenotype, especially in populations with frequent consanguinity [33,41]. For polydactyly with a normal karyotype, Oxford Desk Reference recommends 7-dehydrocholesterol measurement for Smith–Lemli–Opitz and genomic analysis (array, panel, exome or genome) when features suggest a syndrome [18].

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7. Treatments and Risk Management Strategies

7.1 General considerations: absence of aetiological treatment

No pharmacological or gene therapy currently targets Patau syndrome's underlying cause. Complete or near-complete chromosomal aneuploidy provides no single molecular target amenable to pharmacological correction, unlike monogenic disorders [6]. Treatment is therefore symptomatic, supportive and directed towards organ-specific complications, combining neonatal intensive care, indicated surgery, paediatric palliative care and multidisciplinary family-centred support [6,17]. The Brazilian source summarises two principles: surgery depends on the nature and severity of anatomical abnormalities and associated symptoms, and palliative care should minimise suffering and improve quality of life [4].

7.2 Changing ethical and therapeutic approaches (2016–2025)

For decades, the prevailing approach routinely withheld corrective surgery, including congenital heart repair, on the assumption of uniformly poor prognosis. Smith's illustrates this historical position: high infant mortality supports delaying corrective surgical or orthopaedic procedures in early infancy pending the first months' course, and seriously considering limitations on extraordinary life-prolonging measures when severe brain abnormalities are present. It nevertheless emphasises individual assessment and recognition of each child's circumstances and parental feelings [7]. Accumulated population evidence over the last decade has substantially revised this approach. Nelson and colleagues' Ontario population study, published in JAMA in 2016, found that although early mortality remains the commonest outcome in trisomy 13 or 18, 10–13% survive to age 10 and first-year survival is high among children undergoing surgery [45]. Meyer and colleagues' 2016 US multistate birth-defect surveillance study corroborated survival exceeding historical assumptions [46].

This evidence culminated in the AATS 2023 consensus, developed through a structured Delphi process after its Congenital Cardiac Surgery Evidence-Based Medicine working group reviewed more than 500 articles [16]. Its nine central recommendations state that decisions about congenital heart surgery in trisomy 13 or 18 should not depend solely on the chromosome diagnosis. Each case should be assessed using the same clinical and anatomical criteria applied to other children with congenital heart disease [16]. The AAP 2025 clinical report (Pediatrics, August 2025; published online on 21 July) adopted and reinforced this guidance, explicitly finding no ethical justification for differential treatment based exclusively on a genetic diagnosis. The diagnosis nevertheless remains one of several clinical considerations in shared decision-making with families [17]. Teams should explore the full range from comfort care to clinically appropriate treatments, giving these children the same consideration as any child with a complex life-limiting diagnosis, whether expected survival is days, months or years [17,47].

A retrospective single-institution study published in JTCVS Open in 2024 examined 62 patients with trisomy 13 or 18 and congenital heart disease over nearly four decades (1985–2023). It explicitly concluded that trisomy 13/18 alone is not an exclusion criterion for corrective surgery [48]. Ethical controversies remain: AATS consensus authors caution against moving from “never operate” to “always operate”. They advocate balanced individual assessment, empathetic family communication and palliative care as an additional layer of decision support rather than an exclusive alternative to intervention [49].

7.3 System-specific management

Cardiovascular system. Congenital heart disease affects 57–80% and warrants routine neonatal echocardiography [7,8]. Palliative or corrective surgery decisions should follow AATS 2023 principles, considering the specific lesion, pulmonary hypertension (a particularly relevant adverse postoperative prognostic factor, given reports of small pulmonary arterial medial defects associated with fatal pulmonary hypertension in infants with trisomy 13 and 18 [28]), intervention weight and agreed family goals [8,16].

Respiratory system and airway. Central apnoeic episodes are frequent neonatally [7] and may contribute substantially to short life expectancy [3]. Long-term survivors may require secretion management, non-invasive ventilation or tracheostomy; case series describe prolonged survival with structured home respiratory support [50].

Central nervous system and epilepsy. Early, often photosensitive epileptic spasms require targeted EEG assessment. Anticonvulsant treatment follows general infantile epileptic spasm principles, with no validated syndrome-specific drug protocol; paediatric neurology should individualise drug choice [29].

Nutritional support. Feeding difficulty is almost universal. Gastrostomy is often needed in medium- and long-term survivors for adequate nutrition and reduced aspiration risk [17,50]. Gastro-oesophageal reflux and feeding difficulties are nearly invariable, and aspiration during feeding or from reflux may cause cardiorespiratory arrest [3].

Immunisation. Baty and colleagues' natural-history study found no evidence of increased vaccine adverse reactions [7,27].

Cancer surveillance. Unlike trisomies 18 and 21, with established increased embryonal tumour risks (hepatoblastoma and Wilms tumour in trisomy 18; leukaemia in trisomy 21), Satgé and colleagues' 2017 systematic review identified 17 reported Patau-associated neoplasms, including embryonal tumours, leukaemias, malignant germ cell tumours, carcinomas, one malignant brain tumour and one sarcoma. The small reported number did not support increased cancer risk in trisomy 13, distinguishing its profile from trisomies 18 and 21 [51,52]. No targeted routine cancer surveillance is currently recommended [51].

Palliative and family-centred care. The poor prognosis in most cases warrants early paediatric palliative care, integrated alongside active intervention as complementary support throughout the child's and family's care, aligned with collaboratively defined goals [17,49].

The following table summarises the principal management priorities and their rationale.

7.4 Nature of the evidence and principal studies

No randomised intervention trials exist for trisomy 13, and ClinicalTrials.gov lists no therapeutic trials for the condition. The evidence hierarchy requires explicit recognition: the AAP 2025 report is professional society guidance based on literature review and ethical principles [17]; the AATS 2023 consensus uses expert Delphi methodology [16]; available cohorts and meta-analysis are retrospective and provide low-certainty evidence [53]; case reports establish possibilities, not frequencies [54]. None is a regulatory decision, and US recommendations do not bind Portuguese or Brazilian health systems.

These studies do not compare equivalent groups. Operated patients were selected because they survived to surgery, had higher weight and fewer severe abnormalities, and their families and centres chose intervention, introducing selection and immortal-time biases. The meta-analysis odds ratios, with very wide intervals, do not measure causal effects [53]. A relative reduction in in-hospital mortality (45% in Kosiv) does not establish absolute long-term survival; Ignatz-Hoover found intensified inpatient care without reduced neonatal mortality [55,56]. Most surgical series contain few trisomy 13 patients (9 of 62 in Greene), so combined trisomy 13/18 outcomes should not be applied to trisomy 13 alone [48]. Survival medians describe all live births rather than the prognosis of a child who has survived the first months; 10-year survival differs fivefold between complete and mosaic/partial trisomy [57]. Validated quality-of-life measures are lacking.

7.5 Regulatory status of medicines used

No medicine in the United States or European Union has a specific authorised trisomy 13 indication. Drugs used, including antiepileptics, proton pump inhibitors, diuretics and antibiotics, are authorised for general indications and have not been studied in this syndrome. Efficacy is extrapolated from the general paediatric population; whether use is off-label depends on each jurisdiction's drug label, age and indication rather than the chromosomal diagnosis. Respiratory syncytial virus (RSV) prophylaxis is a setting where labels directly cover a frequent problem in these children: haemodynamically significant congenital heart disease.

In the only randomised trial in haemodynamically significant congenital heart disease (palivizumab, 1,287 children), RSV hospitalisations fell from 9.7% with placebo to 5.3%, a relative reduction of 45% and absolute reduction of 4.4 percentage points [59,64]. Nirsevimab and clesrovimab efficacy was demonstrated in healthy preterm and term infants and extrapolated to infants with heart disease from similar pharmacokinetic exposures in palivizumab-comparator trials not powered for efficacy [60,62]. Administration to a child with trisomy 13 and heart disease is therefore on-label, with eligibility based on age, weight and season rather than chromosome diagnosis, and supported by efficacy extrapolation. Clesrovimab in a second season or nirsevimab beyond 24 months would be off-label in both jurisdictions. In Portugal, nirsevimab effectiveness against RSV hospitalisation in 2024–2025 was estimated at 78.5% (95% CI: 59.3–89.0%) in a predominantly non-chronically ill population [65]. In Brazil, regulatory authorisation of an antibody does not establish its incorporation into SUS, which depends on the Ministry of Health and CONITEC.

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8. Reproductive Options and Family Counselling

Reproductive genetic counselling depends on precise mechanistic characterisation of the proband's chromosome abnormality. A complete parental karyotype, rather than CMA or cfDNA results alone, is therefore essential before communicating recurrence estimates [6,39]. As in Down syndrome, infant chromosome analysis identifies rare translocations inherited from a balanced-translocation carrier, for whom recurrence risk is particularly relevant [7]; parental chromosome studies are always indicated for Robertsonian translocations [4,12].

Free trisomy 13 (without translocation). Following spontaneous meiotic nondisjunction without a parental translocation, recurrence risk is 1–2% or the subsequent pregnancy's maternal age-related risk, whichever is higher [24,30]. Oxford Desk Reference estimates approximately 0.5%, citing no recurrence among 46 women with a previous trisomy 13 fetus in a Japanese series (Uehara et al. 1999). It also notes that age-related trisomy 21 risk may exceed trisomy 13 recurrence risk in some women [3]. The risk probably combines maternal age effects and rare parental germline mosaicism undetectable in peripheral blood [30]. De Souza and colleagues' 2009 analysis of trisomies 13, 18 and 21 recurrence supports this order of magnitude, with greater risk when the index trisomy occurred at a younger maternal age [24]. The relative risk of trisomy 13 after a previous affected pregnancy was 9.5, with the largest increase below age 35 at the previous trisomic pregnancy [7].

Parental Robertsonian translocation. A parental chromosome 13 Robertsonian translocation, usually rob(13;14), increases recurrence risk relative to free trisomy, but its magnitude depends on rearrangement type and whether the outcome is conception, prenatal diagnosis or live birth [12,24,30]. For rob(13;14) carriers, Oxford Desk Reference gives a risk of 1% or less per pregnancy of a trisomy 13 live birth. Engels et al. (2008) observed no live births with translocation trisomy 13 in 222 carrier-parent pregnancies (123 female carriers, 71 male carriers, 28 unknown origin), but detected translocation trisomy 13 in 3 of 42 amniocenteses (7.1%). Stillbirth frequencies were 3.3% for female and 1.4% for male carriers. Oxford Desk Reference states “13 of 42 amniocenteses”, inconsistent with the original article. All trisomy 14 conceptions end in early miscarriage, and an additional UPD14 risk is below 0.5% [3,12,66]. Other primary series support low risk: Harris et al. (1979) found no recurrence after the proband's birth in segregation analysis of 86 t(13q14q)-carrier sibships [67]; Daniel et al. (1989), using amniocentesis data from 79 US and Canadian laboratories, estimated 1–2% unbalanced offspring at amniocentesis for rob(13;14) carriers of either sex [68]. Higher figures in other sources, 5–10% affected live births varying with carrier sex [30], or approximately 5% and 20% miscarriage in the Brazilian source [4], are unsupported by these primary series and should not estimate affected live-birth risk. In the extremely rare setting of a homozygous Robertsonian translocation or 13;13 translocation (rob(13q13q)), all viable conceptuses are affected because this configuration cannot produce a balanced or normal karyotype. Almost all conceptions are monosomic or trisomic for chromosome 13, most trisomic pregnancies miscarry, and gamete donation or adoption may enable parenthood [4,12,30]. Specialist clinical genetics referral and alternative reproductive options should routinely be offered, including preimplantation genetic testing (PGT) with in vitro fertilisation, gamete donation, or early prenatal diagnosis with the option of termination within the legal framework and the family's values [6,24].

Risk by heterologous translocation type. The following table reproduces trisomy 13 and UPD14/15 risks for heterologous Robertsonian translocations involving chromosome 13 [12].

* Silverstein et al. (2002) reported 0.65% UPD incidence in fetuses carrying a balanced Robertsonian translocation; because some fetuses have normal karyotypes, overall UPD risk is below 0.5% [12].

De novo Robertsonian translocation. A de novo structural abnormality rarely recurs. With normal parental karyotypes, risk is probably below 2%, based on Steinberg et al.'s 1984 de novo 21q21q Down syndrome data, although recurrence has been reported [3,12]. Polymorphic markers can establish the homologues' parental origin in de novo homologous translocations, since origin determines recurrence risk [12].

Prenatal diagnosis and PGT in carriers. Unlike trisomy 21, trisomy 13 produces more ultrasound-detectable structural abnormalities; at 20 weeks, ultrasound has approximately 90% probability of identifying trisomy 13 features. Given low risk, particularly with miscarriage or subfertility history, amniocentesis may be preferable to chorionic villus sampling for definitive cytogenetic diagnosis [12]. PGT should be considered after three or more miscarriages in couples with a non-homologous Robertsonian translocation, or with oligospermic infertility in a male carrier. When subfertility requires assisted reproduction, PGT usefully screens imbalance even with low viable-abnormality risk, but does not help rob(21q21q) carriers and may miss UPD [12].

Family screening. Chromosome analysis should be offered to at-risk adult relatives. When a translocation is identified prenatally or in a child, the child's record should recommend adolescent genetic counselling, with parents fully informed [12]. A three-generation pedigree should enquire about pregnancy losses, stillbirths, neonatal deaths, infertility, and relatives with learning difficulties or congenital abnormalities [12].

Germline mosaicism. Although recurrence is usually low after sporadic free trisomy 13, two affected pregnancies in one couple should prompt consideration of parental germline mosaicism, a rare circumstance warranting specialist clinical genetics referral [30].

Counselling when the proband is mosaic. Counselling must explicitly acknowledge prognostic uncertainty from the inability to precisely determine trisomic proportions across tissues, particularly the central nervous system, and avoid categorical predictions [2,25]. The Brazilian source categorises mosaic recurrence risk as lower [4].

The following table presents recurrence risk by chromosome abnormality as formulated in the Brazilian source [4].

Communication and shared decision-making. Counselling should be multidisciplinary, ideally involving an obstetrician, clinical geneticist, genetic counsellor, neonatologist and, when relevant, social worker. Non-directive discussion should cover transmission, potential maternal–fetal complications, expected neonatal prognosis, and benefits and limitations of postnatal interventions, respecting individual family circumstances [1]. Oxford Desk Reference lists SOFT UK (Support Organisation for Trisomy 18/13, http://www.soft.org.uk) and Unique (The Rare Chromosome Disorder Support Group, http://www.rarechromo.org) [3,12]. ERN ITHACA (European Reference Network on Rare Congenital Malformations and Rare Intellectual Disability) is the relevant European network, bringing together clinical genetics and dysmorphology centres to support complex-case discussions [11].

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9. Special Considerations: Population Diversity and Epidemiology

9.1 No identified founder effect

Unlike genetic disorders where founder mutations explain high prevalence in geographically or historically isolated populations, the consulted literature describes no trisomy 13 population founder effect. Predominantly sporadic meiotic nondisjunction associated with maternal age, trisomy 13 lacks the marked ethnic variation typical of founder monogenic disorders [1,6]. A partial exception is population frequency of balanced Robertsonian translocations, the structural substrate for translocation trisomy despite not being trisomy 13-specific. Their overall prevalence is approximately 1 in 1,000 newborns, without robustly documented marked ethnic variation specifically for 13;14 [69].

Isolated PAP, usually autosomal dominant with variable expressivity and incomplete penetrance, is approximately 10 times more common in people of sub-Saharan African ancestry. Isolated PAP without other abnormalities therefore has lower predictive value for trisomy 13 in these populations [18].

9.2 Regional epidemiology

Europe. The strongest available registry study, coordinated by EUROCAT (European Surveillance of Congenital Anomalies) across 25 population registries in 16 European countries during 2000–2011, estimated total birth prevalence, including live births, fetal deaths and terminations for fetal anomaly, at 1.9/10,000 (95% CI: 1.8–2.0) [8]. Across 21 EUROCAT registries (6.1 million births, 1990–2009), total prevalence was 2.0/10,000 (95% CI: 1.9–2.2) and live-birth prevalence 0.48/10,000 (95% CI: 0.43–0.54). Total prevalence increased with maternal age while live-birth prevalence remained stable [9]. A subsequent international analysis of 24 registries in 18 countries across Europe, the Americas and Asia, rather than Europe alone, estimated mean total prevalence at 1.68/10,000 (95% CI: 1.3–2.06) in registries including terminations, and live-birth prevalence at 0.55/10,000 (95% CI: 0.38–0.72), higher where termination was prohibited [70]. In the European cohort, affected live births had cardiac abnormalities in 57%, nervous system abnormalities in 39%, ocular abnormalities in 30% and polydactyly in 44% [8]. Termination for fetal anomaly accounted for 73% of identified European cases, demonstrating widespread prenatal screening's direct effect on observed birth epidemiology [8]. Parker and colleagues (2003) described epidemiology, genetics and prenatal diagnosis in a defined UK population [3], while a ten-year Danish study by Goldstein and Nielsen (1988) documented trisomy 13 and 18 rates and survival [71].

United States. National Birth Defects Prevention Network multistate surveillance suggests prevalence of similar magnitude to Europe. Paediatric references estimate approximately 1 in 18,000 live births for complete forms [72], while broader estimates including partial and mosaic forms reach 1 in 5,000 to 1 in 10,000 [1,73].

Japan. In addition to intensive-treatment survival data (section 11), a Japanese series of 1,076 mothers (Uehara et al. 1999) recorded no recurrence among 46 women with a previous trisomy 13 fetus [3].

Brazil and Latin America. Regional data are substantially more limited than European and North American data. Petry and colleagues' Brazilian 2013 series in Rio Grande do Sul characterised clinical manifestations and prognosis, providing one of the region's few systematic datasets [74]. Síndromes Genéticas: Reconhecer para Tratar gives incidence of 1/7,000 births without specifying the population underlying the estimate [4]. However, the search identified no Latin American population birth-prevalence registries comparable in methodological strength to EUROCAT or US state surveillance, a gap that should be acknowledged when communicating regional epidemiology. The international 24-registry analysis included South American hospital registries: ECLAMC (Latin American Collaborative Study of Congenital Malformations, 237 trisomy 13 cases during 1995–2014), Argentina's RENAC and Colombian registries, with follow-up limited to hospitalisation and no separate Brazilian prevalence [70]. Other Brazilian referral-centre series describe treated patients rather than prevalence: a São Paulo quaternary university hospital (2014–2018) reported 83% in-hospital mortality among six intensive-care newborns with trisomy 13 and heart disease [75]; in an ECLAMC-participating high-fetal-risk Rio de Janeiro maternity unit (2018–2023), Patau syndrome accounted for 10 of 95 newborns with congenital heart disease and a genetic syndrome [76].

Portugal. The National Registry of Congenital Anomalies (RENAC), maintained by Instituto Nacional de Saúde Doutor Ricardo Jorge, is population-based and follows EUROCAT standards. It documented prenatal diagnosis in 56.1% of registered congenital anomaly cases during 1997–2016 [77]. The consulted sources contained no publication specifying Portugal's trisomy 13 prevalence; this does not mean the registry lacks such data.

Africa, Asia and the Middle East. The search identified no robust, systematic population-prevalence registries specifically addressing trisomy 13 in these regions. Available literature consists predominantly of isolated cases or small hospital series, including reports from Morocco [31] and Palestine [78], insufficient for reliable population prevalence estimates. This recognised limitation of rare-aneuploidy epidemiology outside Europe and North America should be acknowledged rather than filled through extrapolation.

9.3 Special populations

Consanguinity. In populations with frequent consanguineous marriage, the principal differential challenge is distinguishing true trisomy 13 from autosomal recessive pseudotrisomy 13, which closely reproduces its malformation phenotype without a chromosomal cause. Cytogenetic confirmation remains mandatory even for apparently unequivocal cases [33]. Consanguinity also suggests ciliopathies such as Meckel–Gruber, hydrolethalus, Bardet–Biedl and Joubert in syndromic polydactyly differentials [18].

Long-term survivors. A small but clinically relevant subgroup comprises long-term survivors. Survival to 33 years was reported in the original series [7], and newer reports describe adult survival with structured multidisciplinary support [79]. Female sex and trisomic mosaicism are associated with prolonged survival [3,50]. Specific care challenges include paediatric-to-adult transition and anaesthetic considerations, particularly difficult-airway risk after previous palatoplasty, documented in adult elective-surgery case reports [79].

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10. Illustrative Clinical Case

10.1 Composite vignette

The following educational composite vignette draws on presentation and clinical course in published series of long-term trisomy 13 survivors [50,54].

A female newborn was born following the second pregnancy of a 38-year-old mother without consanguinity. First-trimester cfDNA screening indicated high trisomy 13 risk, confirmed by amniocentesis showing 47,XX,+13. Second-trimester anomaly ultrasound identified semilobar holoprosencephaly, bilateral hand postaxial polydactyly and a ventricular septal defect. After multidisciplinary genetic counselling, the parents continued the pregnancy with an individual care plan coordinating neonatology, paediatric cardiology and paediatric palliative care prenatally.

Birthweight was 2,350 g, consistent with mild growth restriction. Findings included microcephaly, bilateral cleft lip, right microphthalmia, narrow hyperconvex nails and 1.5 cm occipital aplasia cutis congenita. Cardiac examination confirmed a moderate perimembranous ventricular septal defect without significant immediate neonatal haemodynamic effects. Renal ultrasound showed mildly increased cortical echogenicity without definite polycystic kidney criteria. Recurrent central apnoea in the first weeks was managed with non-invasive respiratory support.

Following AATS 2023 and AAP 2025 principles, septal-defect closure was individualised according to specific anatomy, absence of significant pulmonary hypertension at catheterisation, and family goals rather than automatically determined by chromosome diagnosis alone. Elective repair at four months had no major postoperative complications.

At eight years, the child had severe intellectual disability, no verbal language, communication through facial expressions and vocalisations, and partially controlled seizures on combined anticonvulsants. Persistent dysphagia required gastrostomy feeding; recurrent respiratory infections required regular paediatric respiratory follow-up. Physiotherapy, occupational therapy and sensory stimulation were structured. The family perceived quality of life as satisfactory with highly organised home care, paediatric palliative support and family organisations such as the Support Organization for Trisomy 18, 13 and Related Disorders (SOFT) [13].

The vignette illustrates three principles: prenatal cfDNA increasingly enables anticipatory care planning; contemporary surgery decisions are individualised rather than categorical; and prolonged survival with positively perceived family quality of life is increasingly documented over the last decade when structured multidisciplinary support and palliative care are integrated from pregnancy [17,50,54].

10.2 Published case: an 8-year-old child with complete trisomy 13

Aleksander and colleagues reported in 2025 a girl with complete trisomy 13 (47,XX,+13), diagnosed by amniocentesis at 21 weeks after low first-trimester PAPP-A and increased nuchal translucency in a UK-managed pregnancy [54]. She was born at 35+4 weeks, weighing 2,087 g with head circumference 31 cm, without resuscitation. Findings were omphalocele repaired on day three, cleft lip and palate, hypertelorism, low-set ears, aplasia cutis, microcephaly, overlapping fingers and rocker-bottom feet, without polydactyly or renal abnormalities. Echocardiography showed ventricular and atrial septal defects, patent foramen ovale and a bicuspid aortic valve without haemodynamic effects; the septal defects closed partially or completely spontaneously. Discharge on day 15 involved nasogastric feeding. Myoclonic seizures began at 3 months and were controlled with two antiepileptics; hearing aids were used from 6 months despite unrecordable auditory brainstem responses. Percutaneous endoscopic gastrostomy at 3 years addressed persistent growth failure (102 cm and 12.2 kg at 8 years, below the 0.4th percentile). Cleft lip repair occurred at 5 years; nephrocalcinosis detected at 6 years was not investigated further by parental choice. Several pneumonia admissions and daily secretion suctioning were required. At 8 years, she attended a school with specialist support, remained fully dependent with no speech and severe cognitive impairment, but rolled, sat with support, used a standing frame and responded to speech with smiles and laughter. Open-access photographs show infancy (cleft lip, trigger thumbs, rocker-bottom feet; figure 1), hospitalisation at 7 years (figure 2) and daily activities (figure 3) (https://pmc.ncbi.nlm.nih.gov/articles/PMC12732030/) [54].

This course is not typical: she belongs to the minority of long-term survivors (4.9–12.9% 10-year survival in population cohorts), without described holoprosencephaly and with heart disease not requiring surgery [45,57]. The authors partly attribute survival to multidisciplinary follow-up, but this is a single-case interpretation. Avoiding neuroimaging under anaesthesia or further nephrocalcinosis investigation reflected shared palliative decisions with the family, not general recommendations.

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11. Prognosis and Long-Term Follow-up

Overall prognosis remains poor, although large population studies have refined survival estimates substantially over two decades. Intrauterine mortality exceeds 95% of affected conceptuses [6]. Historical median survival without intensive intervention is seven days, with 91% first-year mortality in the Smith's synthesis of Baty and colleagues and Goldstein and Nielsen [7,71,80]. Rasmussen and colleagues' 2003 population study reported median survival of 7–10 days and 5–10% survival beyond 12 months [3,10]. Hsu and Hou (2007) described median survival of 95 days, noting that infants without holoprosencephaly or omphalocele were less likely to miscarry or be prenatally detected and survived longest [3]. More recent population analyses reflecting more active medical and surgical intervention report somewhat better outcomes: Nelson and colleagues (2016) found 10–13% survival to age 10 and high first-year survival among operated children [45]. The international 24-registry analysis found median first-week mortality of 48%, half on day one, and first-year mortality of 87% in registries with complete follow-up, with approximately 7% cumulative 5-year survival [70]. In Texas, 8.5% of 295 affected live births from 1999–2008 survived to 10 years: 4.9% with complete trisomy and 25.0% with mosaic/partial trisomy. Non-complete status explained 41.7% of 10-year survival as a population attributable fraction [57]. These figures apply to all live births in each registry and should not be transferred between cytogenetic subtypes. A Japanese study cited in case literature reported median life expectancy up to 733 days with intensive treatment, including resuscitation and surgery, in selected series [81].

The Brazilian source conversely states that improved medical care has not substantially changed survival and provides the following age-specific proportions. Although its table is headed “death frequency”, the values agree with the population series above as survivor proportions [3,4,10]:

Poorer survival is associated with male sex, preterm birth and major congenital heart disease, particularly with pulmonary hypertension [49,81]. Female sex and trisomic mosaicism conversely favour prolonged survival; children surviving beyond average are more likely to be mosaic [3,50]. Cardiorespiratory arrest is the commonest cause of death, and central apnoea may contribute to short life expectancy [3]. US hospital surveillance of affected live births during 2003–2018 found 58% neonatal mortality without a statistically significant improvement over time despite significantly increasing mean length of stay. This suggests intensified intervention without consistent overall mortality improvement and reinforces candid, individualised discussion of realistic expectations [56].

Medium- and long-term survivors commonly have severe intellectual disability, often no verbal language, seizures of variable severity and failure to thrive, findings established in the original Patau series and repeatedly confirmed [7,80]; most do not achieve normal developmental milestones [4]. Among Baty and colleagues' surviving children, mean neonatal intensive-care duration was 10.8 days, mean mechanical ventilation duration 13.3 days, and 23% underwent neonatal surgery [7,27]. Structured follow-up should be systematic and multidisciplinary, including periodic cardiology, respiratory care for recurrent infection prevention and management, regular nutritional assessment often requiring gastrostomy, neurology to optimise seizure control, serial hearing and eye assessments, and physiotherapy, occupational therapy and early stimulation [17,50]. Trisomy 13-specific growth charts derived from Baty and colleagues' study are available to guide anthropometric follow-up [27,80].

Established in 2007, Tracking Rare Incidence Syndromes (TRIS) systematically collects family-centred natural-history data for rare trisomies, including trisomy 13, and provides information to families and interested healthcare, education and therapy professionals [7]. SOFT (Support Organization for Trisomy 18, 13 and Related Disorders) complements this work as an international network connecting families and professionals for diagnostic and ongoing care support [13].

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12. Summary and Final Considerations

Patau syndrome is the third most common major autosomal aneuploidy among live births. Most cases reflect complete free chromosome 13 trisomy following maternal meiotic nondisjunction; Robertsonian translocations and postzygotic mosaicism make smaller but clinically consequential contributions. The clinical triad of orofacial defects, microphthalmia and postaxial polydactyly within the wider holoprosencephaly spectrum reflects early disruption of prechordal mesoderm morphogenesis. ZIC2 at 13q32 is the best-characterised molecular candidate, although the overall phenotype results from cumulative chromosome-wide gene dosage rather than a single monogenic pathway.

Contemporary care has shifted from routine therapeutic withholding to individualised decisions, consolidated during 2016–2025 by population evidence and professional consensus (AATS 2023, AAP 2025). Decisions integrate family goals, case-specific clinical evidence and palliative care as a complement to active treatment. This change does not remove the condition's severity or poor prognosis in most cases, but provides an ethically and clinically grounded framework for shared family decisions.

Widespread prenatal cfDNA screening, unanimously recommended by major international societies regardless of baseline risk, increasingly advances diagnosis into pregnancy. Medical genetics professionals must communicate risk earlier, precisely and sensitively to family circumstances. For reproductive counselling, the proband karyotype distinguishes low free-trisomy recurrence risk (approximately 0.5–2%) from translocation risk, which depends on rearrangement type: below 1% affected live births in rob(13;14) carriers and almost universal involvement in rob(13q13q) carriers [3,12]. Knowledge gaps remain, particularly robust population epidemiology outside Europe and North America. These limitations require transparent acknowledgement in clinical practice and publications and warrant further epidemiological research, especially in Latin America, Africa and Asia.

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Reference figures (attached primary source)

The classical clinical figures in the “Trisomy 13 Syndrome” chapter of Smith's Recognizable Patterns of Human Malformation provide the syndrome's reference images: newborn photographs illustrating the sloping forehead and variable facial development (Figure 1, Smith's, p. 16), and hyperconvex nails, postaxial polydactyly, occipital aplasia cutis congenita and scrotalisation of the phallus (Figure 2, Smith's, p. 17) [7]. The Brazilian reference includes a G-banded karyotype of a male with free chromosome 13 trisomy (Figure 1.3.1) and the faces of three children with different phenotypic severity, scalp aplasia and polydactyly (Figure 1.3.2, authors' personal archive) [4]. Additional freely accessible clinical images are available in the following open-access articles, with figures linked directly within the article HTML:

• Bahari H, et al. Trisomy 13 With Bilateral Congenital Anophthalmia: A Case Report. Cureus 2024 — https://pmc.ncbi.nlm.nih.gov/articles/PMC11170545/
• Beyond the Diagnosis: A Journey of an 8-Year-Old Girl with Patau Syndrome. Children 2025 — https://www.mdpi.com/2227-9067/12/12/1632
• Gandhi J, et al. A 29-Year-Old Patient With Patau Syndrome. Cureus 2024 — https://pmc.ncbi.nlm.nih.gov/articles/PMC10829937/

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