Microphthalmia, Syndromic 3

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

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.

Treatment
Treatment Options: 

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.

References
Article Title: 

References

Salem NJ, Hempel M, Heiliger KJ, Hosie S, Meitinger T, Oexle K. Anal Atresia, Coloboma, Microphthalmia, and Nasal Skin Tag in a Female Patient with 3.5 Mb Deletion of 3q26 encompassing SOX2. Am J Med Genet A. 2013 Apr 23. [Epub ahead of print].

PubMedID: 23613260

Fiorenza M, Toutain A, Calvas P. Germinal mosaicism and familial recurrence of a SOX2 mutation with highly variable phenotypic expression extending from AEG syndrome to absence of ocular involvement. Am J Med Genet A. 2007 Feb 1;143(3):289-91.

PubMedID: 17219395

Hagstrom SA, Pauer GJ, Reid J, Simpson E, Crowe S, Maumenee IH, Traboulsi EI. SOX2 mutation causes anophthalmia, hearing loss, and brain anomalies. Am J Med Genet A. 2005 Oct 1;138A(2):95-8.

PubMedID: 16145681