Trisomy 13

From EyeWiki

Disease Entity

Trisomy 13, also known as Patau Syndrome, is a disorder of fetal maldevelopment with wide-ranging and often severe developmental manifestations, including ocular malformations. The disorder was first described by Patau, et al., in 1960 as "cerebral defects, apparent anophthalmia, cleft palate, hare lip, simian creases, trigger thumbs, polydactyly, and capillary hemangiomata."[1]


Trisomy 13 is an aneuploidy (less or more than 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, affecting approximately 80% patients.[2][3][4] A vast majority, approximately 91%, of trisomy 13 cases are due to nondisjunction in the female gamete.[5][6]

Translocation trisomy 13, “when part of chromosome 13 becomes attached (translocated) to another chromosome during the formation of eggs or sperm, or very early in fetal development” accounts for ~20% of cases. This results in two normal copies of chromosome 13 and an extra copy of chromosome 13 attached to another chromosome. Translocation trisomy 13 can be inherited.[3]

Mosaic trisomy 13 occurs when some cells contain euploid genomes and others contain aneuploid genomes. Mosaicism accounts for 5% of trisomy 13 cases.[7] The phenotypes of such cases are 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.[8]

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.[9]


Phenotypes that arise from aneuploidy are thought to occur due to abnormal levels of gene expression involving genes of the duplicated chromosome.[3][8] The following fetal developmental processes are thought to be disrupted during eye development in trisomy 13:[10]

  • 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 estimated prevalence of trisomy 13 is 1:5,300 in Europe[11] and 1:14,000 in the United States.[12] It is the third most common autosomal trisomy in newborns after trisomy 21 and trisomy 18[13][14] and is considered to be the most lethal of the three[15]. Only 6-12 % of infants with trisomy 13 survive beyond the first year of life. [4]It appears to affect females slightly more frequently than males.[3] 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.[14] Most cases are not inherited.[3]

Clinical Features

Systemic Manifestations

Complete trisomy 13 typically results in malformations of multiple organ systems and severe intellectual disability.[3] Common findings include: microcephaly, cleft lip and/or palate, polydactyly, hypotonia, failure to thrive, feeding difficulties, cutis aplasia (i.e. missing skin), capillary hemangiomas, low-set ears, deafness, cardiac, brain (holoprosencephaly), spinal cord, and genitourinary anomalies.[8][11][16] Trisomy 13 is the most common cause of holoprosencephaly, which causes severe abnormalities of midline facial structures.[17] Many other systemic features of trisomy 13 have been described.[2][3]

Ocular Manifestations

Figure 1: anophthalmia

The incidence of any particular ocular finding is difficult to ascertain due to the rarity of the disorder and the brief lifespan of affected individuals. These clinical signs have been reported in 80-99% of people with trisomy 13[2]:

Figure 2: iris coloboma

These clinical signs have been reported in 30-79% of individuals with trisomy 13[2]:

  • Abnormal eyelash morphology[2]
  • Aplasia/hypoplasia of the iris (aniridia)[21]
  • Congenital cataract 6% [11][16][19]
  • Deeply set eye[2]
  • Iris coloboma (usually inferonasal 33% [16] [19]Figure 2)
  • Optic atrophy[2]
  • Retinal dysplasia[22][23]
Figure 3: persistent fetal vasculature (PFV). Reproduced with permission from[24] under a Creative Commons license.

Other reported findings include:

  • Acute elevation of intraocular pressure[7]
  • Cartilaginous mass of the anterior segment[16][18]
  • Ciliary body coloboma[23]
  • Coats disease (retinal telangiectasias)[16]
  • Congenital glaucoma/buphthalmos 1% [21][25][26][19]
  • Corneal opacity[18]
  • Cyclopia[17][22]
  • Dysgenesis of the anterior segment[22][27]
  • Epicanthal folds[28]
  • Nasolacrimal duct obstruction[29]
  • Optic nerve coloboma[30]
  • Persistent fetal vasculature (PFV, Figure 3)[16][24]
  • Persistent tunica vasculosa lentis (PTVL)[16]
  • Sparse or absent eyebrows
  • Upslanting palpebral fissures[20]
  • Keratoconus[31]


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.[2][32] It is associated with increased fetal nuchal translucency, decreased PAPP-A, and decreased β-hCG during first trimester screening.[33] 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, aggressive medical and surgical ophthalmic care is generally not advised and palliative/supportive care options are preferred. However, for patients with better prognoses and eye conditions amenable to medical or surgical intervention, treatments may be considered.[16][29][34] In one study, among children who underwent surgery, 1-year survival was 68.6%.[35]More recently there has be a trend in aggressive medical and surgical management leading to increased survival rates and life expectancy in patients with trisomy 13.[19] More aggressive care downstream for other organ systems, including the eye, may also rise in the future.


Many cases of trisomy 13 end in spontaneous abortion (49% in one study[36]), and most of those born with the condition have a very limited life expectancy. Approximately 50% of affected infants do not survive beyond the first month, with a higher fatality rate for males.[2][37][38][4] According to one study, ten-year survival for trisomy 13 was 12.9%. In another study, among affected individuals who lived beyond one year, five-year survival was 84%.[38] The most common causes of death are cardiopulmonary arrest (69%), complications of congenital heart disease (13%), and pneumonia (4%).[37]


Trisomy 13, or Patau Syndrome, is a severe developmental disorder that results in anomalies in multiple organ systems and poor rate of survival. Ocular pathology is common and varies widely among individuals. Common ocular abnormalities include: anophthalmos/microphthalmos, congenital cataract, hypo- or hypertelorism, and inferonasal iris coloboma; but many other ocular findings have been reported.[11][16][18][20][22][21][30][29]

Additional Resources


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