Trisomy 13 (Patau syndrome) is a chromosomal abnormality in which there are three copies of chromosome 13. It was first reported by Patau et al. in 1960. It involves extensive multiple malformations including eye abnormalities and severe intellectual disability.
It is the third most common autosomal trisomy and the most lethal. The incidence is 1 in 5,000 to 12,000 live births, reported as 1:5,300 in Europe and 1:14,000 in the United States 6). It is slightly more common in females. Most cases are non-inherited and occur sporadically.
The median survival is about 10 days, with 28% dying within the first week, 44% within one month, and 86% within one year 5). The 5-year survival rate is reported as 9.7% and the 10-year survival rate as 12.9% 7). Main causes of death are cardiopulmonary arrest (69%), complications of heart disease (13%), and pneumonia (4%).
The median survival is about 10 days, with 40% surviving to one month and about 10% to one year. The 5-year survival rate is reported as 9.7% and the 10-year survival rate as 12.9%. Recent reports indicate that with aggressive treatment, the 1-year survival rate can reach 68.6%, and mosaic, partial, female, and full-term infants tend to have a better prognosis.
It is discovered as an external malformation at birth or during the neonatal period. Because the child has severe intellectual disability, they usually do not complain of visual symptoms.
Ocular lesions are observed in approximately 50% of cases and present clinically significant findings6).
High frequency (80–99%)
Microphthalmia/anophthalmia: Seen in 60–88% of complete type and 23% of mosaic type4). Cases have been reported where the eyeball cannot be clinically identified but MRI reveals ocular structures.
Ocular distance abnormality: Shortened interocular distance in 83% of complete type and 67% of mosaic type4).
Moderate frequency (30–79%)
Coloboma/cataract: Present in 63–75% of complete type and 10–11% of mosaic type4). Iris coloboma is typically located inferonasally and occurs in about 33% of all cases.
Others: Eyelash abnormalities, iris hypoplasia, deep-set eyes, optic atrophy, retinal dysplasia.
In complete trisomy 13, microphthalmia/anophthalmia occurs in 60–88%, coloboma/cataract in 63–75%, and hypotelorism in 83%, all at very high frequencies. In mosaic trisomy 13, microphthalmia occurs in 23% and coloboma in 10–11%, which are milder. Overall, about 50% of patients have clinically significant ocular findings.
Trisomy 13 is caused by a numerical abnormality of chromosome 13. There are the following four types.
| Type | Frequency | Mechanism | Features |
|---|---|---|---|
| Complete type | Approximately 80% | Meiotic nondisjunction (91% maternal origin) | Typical severe presentation |
| Translocation type | Approximately 20% | Robertsonian translocation | May be inherited |
| Mosaic type | Approximately 5% | Mitotic nondisjunction | Mild symptoms5) |
| Partial type | Rare | Partial duplication | Mild |
The main risk factor is advanced maternal age, with a marked increase after age 35.
Factors associated with long-term survival include mosaic type, partial type, female sex, and full-term birth3)7).
Mosaic type is often milder than complete type. Microphthalmia occurs in 60–88% of complete type versus 23% in mosaic type; coloboma and cataract occur in 63–75% of complete type versus 10–11% in mosaic type. Survival tends to be longer, and cases of mosaic type surviving to 6 years of age have been reported.
| Test | Timing | Details |
|---|---|---|
| Fetal Ultrasound | First to Second Trimester | Detection of holoprosencephaly, hypotelorism, increased lens echogenicity, and cardiac malformations1) |
| Maternal serum screening | First trimester | Increased NT, decreased PAPP-A, decreased β-hCG |
| Noninvasive prenatal testing (NIPT) | From 10 weeks | For screening purposes; insufficient for definitive diagnosis |
| Amniocentesis / Chorionic villus sampling | 15–20 weeks / 10–13 weeks | Definitive diagnosis by karyotype analysis |
Based on clinical features (combination of multiple malformations), suspect trisomy 13 and confirm by peripheral blood karyotype analysis.
Even if clinically judged as anophthalmia, MRI may reveal residual ocular structures, so imaging evaluation is useful.
Trisomy 13 has a poor prognosis, so aggressive treatment was often not indicated in the past. However, in recent years, advances in neonatal intensive care and cardiac surgery have improved the prognosis.
In 2023, the AATS (American Association for Thoracic Surgery) indicated a policy recommending individualized treatment plans for children with trisomy 13.
Due to the issue of life prognosis, aggressive ophthalmologic treatment is often not performed, but in recent years, with prolonged survival, treatment for intervenable eye diseases such as glaucoma and cataract is being considered. It is determined individually, taking into account the child’s overall condition and prognosis.
The phenotype of trisomy 13 is caused by abnormal expression of genes on the duplicated chromosome 13. Abnormalities during eye development result in different phenotypes depending on the timing of the disruption.
Gestational Weeks 3–4
Optic pit → optic vesicle formation period: Disruption at this stage leads to anophthalmia. The process of the optic sulcus extending outward to form the optic vesicle is inhibited.
Gestational Weeks 4–6
Lens vesicle and optic cup formation period: Aphakia, cystic eye, and disorganization of retinal layers may occur. Failure of closure of the embryonic fissure at week 6 causes coloboma, microphthalmia, and nuclear cataract.
Embryonic weeks 7–12
Development of secondary lens fibers, vitreous, and neural crest cells: Anterior segment dysgenesis occurs. During weeks 10–12, the iris and ciliary body develop, and zonular cataracts or anterior segment anomalies may arise.
Incomplete regression of the tunica vasculosa lentis causes persistent fetal vasculature.
Holoprosencephaly is a disorder of forebrain division, occurring in 24–45% of trisomy 13 cases 1). Ocular hypotelorism is closely associated with holoprosencephaly, and ultrasound may detect hypotelorism and increased lens density 1).
Moran-Barroso et al. (2021) reported a case of a 12-year-old girl with a mixture of mosaic and partial types. She showed a complex karyotype, suggesting involvement of chromothripsis (chromosome shattering and rearrangement) 4).
Albar et al. (2021) reported a 6-year-old boy with mosaic trisomy 13 who had only mild ocular findings of deep-set eyes and small palpebral fissures 5). This case demonstrates the phenotypic diversity of the mosaic type.
Kramer et al. (2022) reported a long-term survival case of a patient with full trisomy 13 who survived until adolescence, showing the effect of active management 7).
McTaggart et al. (2021) reported a case of a 35-month-old child under ophthalmologic follow-up for microphthalmia, glaucoma, and cataract 3). The importance of ophthalmologic management is increasing in long-term survivors.
In the future, as indications for aggressive treatment expand, the demand for ophthalmologic care for long-term survivors may increase.
