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Microphthalmia, Syndromic 3

OMIM ID:

autosomal dominant

Microphthalmia, Syndromic 3

Alternate Names

MCOPS3
AEG syndrome
microphthalmia and esophageal atresia syndrome
anophthalmia-esophageal-genital syndrome

Defective Genes

SOX2

Clinical Characteristics

Ocular Features

Microphthalmia or clinical anophthalmia is the major ocular malformation in this disorder but optic nerve hypoplasia or even aplasia may also be present.  Colobomas and congenital cataracts may be seen.

Systemic Features

Esophageal atresia and sometimes tracheoesophageal fistula sometimes coexist. The ears can be low-set and malformed and sensorineural hearing loss is often present.  Facial palsy has been reported.  The penis may be small and combined with cryptorchidism while physical growth retardation is common.  Other less common malformations include cleft palate, vertebral anomalies, cardiac anomalies, body asymmetry, and microcephaly.  A few patients have had radiologically evident CNS malformations such as dilated ventricles, hippocampal hypoplasia, abnormal white matter, and holoprosencephaly.  However, intellectual development and function have been normal in other patients.

Genetics

Inheritance

This is an autosomal dominant disorder secondary to heterozygous mutations in the SOX2 gene (3q26.33).  Chromosomal aberrations involving this region of chromosome 3 have also been found.

Pedigree

Autosomal dominant

Autosomal dominant disorders require only one mutation for the disease to be expressed.  Since an affected parent has two chromosomes, only one of which has the mutant gene, parents can expect that half (50%) of their children will receive that one and inherit the disease.  It is common for individuals that inherit the mutation, however, to not have evidence of the disease (nonpenetrance).

Image
Sample pedigree of autosomal dominant inheritance

Autosomal dominant inheritance leads to a vertical pattern of transmission

Treatment & Management

Depending upon the severity of malformations, life expectancy can be normal but some patients have died in the neonatal period.  Certain defects such as those of the heart, palate and esophagus can be surgically repaired.  Hearing device can be helpful but no treatment is available for the eyeball malformations.

Publications

Displaying 1 - 3 of 3

Anal atresia, coloboma, microphthalmia, and nasal skin tag in a female patient with 3.5 Mb deletion of 3q26 encompassing SOX2

PubMedID: 23613260

Germinal mosaicism and familial recurrence of a SOX2 mutation with highly variable phenotypic expression extending from AEG syndrome to absence of ocular involvement

PubMedID: 17219395

SOX2 mutation causes anophthalmia, hearing loss, and brain anomalies

PubMedID: 16145681