Trisomy 13, also known as Patau Syndrome, is a disorder of fetal development with wide-ranging and often severe developmental manifestations. The disorder was first described by Patau, et al., in 1960. Ocular malformations are commonly observed in patients with Trisomy 13.
Trisomy 13 is an aneuploidy (lacks 46 chromosomes) in which three copies of chromosome 13—instead of the typical two—are present. Complete, mosaic, and partial forms of trisomy 13 exist. A complete trisomy occurs when a chromosomal nondisjunction happens during meiosis, a process that occurs in sex cells before fertilization. In such cases, all cells in an organism fertilized by the aneuploid sex cell will harbor an aneuploid genome. Complete trisomy 13 is the most common form of the disorder. The vast majority of trisomy 13 cases are due to nondisjunction in the female gamete.
Mosaic trisomy 13 occurs when some cells contain euploid genomes and others contain aneuploid genomes. Phenotypes of such cases is generally less severe. Mosaicism occurs due to nondisjunction during mitosis, the process of cell division during development. Only cells derived from the errant cell will harbor extra copies of the chromosome. Partial trisomy 13 occurs when cells contain two full copies plus an additional portion of chromosome 13. Phenotypes of partial trisomy 13 are also less severe than the complete form.
Phenotypes that arise from aneuploidy are thought to occur due to abnormal levels of gene expression involving genes of the duplicated chromosome. The following fetal developmental processes are thought to be disrupted during eye development in trisomy 13:
- Organogenesis (third-fourth weeks): optic pit changes into the optic vesicle
- Potential abnormality in trisomy 13: anophthalmia
- End of fourth week: lens pit and vesicle appear, optic vesicle invaginates to form optic cup
- Potential abnormalities in trisomy 13: aphakia, congenital cystic eye, disturbed retinal lamination
- Sixth week: fetal fissures close; lens separates from surface and primary fibers form, retinal differentiation begins, tunica vasculosa begins
- Potential abnormalities in trisomy 13: coloboma, microphthalmia with orbital cysts, nuclear cataract
- Seventh-ninth weeks: secondary lens fibers form, secondary vitreous forms, neural crest cells grow into the anterior segment
- Potential abnormalities in trisomy 13: nuclear cataract, anomalies of the retina and/or vitreous, anterior segment dysgenesis
- Tenth-twelfth weeks: secondary lens fibers progress, development of ectodermal layers of iris and ciliary body begins
- Potential abnormalities in trisomy 13: zonular cataract, malformations of anterior segment
The prevalence of Trisomy 13 is between 1 in 5,000 and 1 in 29,000 live births and is the third most common autosomal trisomy in newborns after trisomy 21 and trisomy 18. Estimated prevalence of trisomy 13 is 1:5,300 in Europe and 1:14,000 in the United States. The clearest risk factor for fetal aneuploidy is advanced maternal age, as the risk begins to increase significantly after a maternal age of 35 years for trisomies 13, 18, and 21.
Complete trisomy 13 typically results in malformations of multiple organ systems and severe intellectual disability. Common findings include microcephaly; cleft lip and palate; polydactyly; cutis aplasia; and cardiac, CNS, and genitourinary anomalies. Trisomy 13 is the most common cause of holoprosencephaly, which causes severe abnormalities of midine facial structures. Many other systemic features of trisomy 13 have been described.
Ocular abnormalities are present in approximately 30% of live-born neonates. While the incidence of any particular ocular findings is difficult to ascertain due to the rarity of the disorder and the brief lifespan of affected individuals, anophthalmos/microphthalmos (Figure 1), congenital cataract, and iris coloboma (usually inferonasal, Figure 2) are common. Other reported findings include:
- Ciliary body coloboma
- Persistent fetal vasculature (PFV, Figure 3)
- Persistent tunica vasculosa lentis (PTVL)
- Congenital glaucoma/buphthalmos
- Dysgenesis of the anterior segment
- Cartilaginous mass of the anterior segment
- Corneal opacity
- Optic nerve coloboma
- Retinal dysplasia
- Coats disease (retinal telangectasias)
- Nasolacrimal duct obstruction
- Upslanting palpebral fissures
- Hyper- or hypotelorism
Trisomy 13 may be suggested or diagnosed with prenatal screening and testing using fetal ultrasound, biochemical and molecular testing of maternal blood, amniocentesis, and chorionic villus sampling. Postnatal diagnostic genetic testing may be undertaken if features of the syndrome are suspected in an infant who was not diagnosed in the prenatal period.
Given the limited life expectancy for most patients with trisomy 13, ophthalmic surgery is generally not recommended. However, for patients with better prognoses and eye conditions amenable to surgical intervention, surgery may be considered.
Many cases of trisomy 13 (49% in one study) end in spontaneous abortion, and most of those born with the condition have a very limited life expectancy. 75-80% of affected infants do not survive beyond the first month, with a higher fatality rate for males. However, some affected individuals live much longer. In one study, among affected individuals who lived beyond one year, five-year survival was 84%. The most common causes of death are cardiopulmonary arrest (69%), complications of congenital heart disease (13%), and pneumonia (4%).
Trisomy 13, or Patau Syndrome, is a severe developmental disorder that results in developmental anomalies in multiple organ systems. Ocular pathology is common and varies widely among individuals. Common findings include anophthalmos/microphthalmos, congenital cataract, and inferonasal iris coloboma, but many other findings have been reported.
- Chromosome Disorder Outreach (CDO): https://chromodisorder.org
- Hope For Trisomy: https://www.hopefortrisomy13and18.org
- Support Organization for Trisomy 18, 13, and Related Disorders (SOFT): https://trisomy.org
- Unique – Rare Chromosome Disorder Support Group: https://www.rarechromo.org
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