Microphthalmia, Isolated, With Coloboma 5

A number sign (#) is used with this entry because of evidence that isolated microphthalmia with coloboma-5 (MCOPCB5) is caused by heterozygous mutation in the Sonic hedgehog gene (SHH; 600725) on chromosome 7q36.

For a discussion of genetic heterogeneity of isolated colobomatous microphthalmia, see MCOPCB1 (300345).

Clinical Features

Schimmenti et al. (2003) examined an 8-month-old boy with bilateral microphthalmia, bilateral inferonasal coloboma of the iris, a right-sided chorioretinal coloboma involving the entire optic disc and extending into the fovea, and a left-sided uveoretinal coloboma sparing the optic disc and macular area. The boy had no stigmata of holoprosencephaly or other anomalies or malformations, and on follow-up at age 11 years, he was an honors student with no serious medical illnesses. The mother of the proband was initially believed to be phenotypically normal, but thorough ophthalmic examination revealed a subtle right-sided inferonasal iris defect and a minimal uveoretinal coloboma, with a normal left eye. She had no findings suggestive of a syndromic malformation. Examination of the father, a brother, and other family members showed no ocular or other physical defects.

Molecular Genetics

In a boy with bilateral colobomatous microphthalmia, Schimmenti et al. (2003) identified heterozygosity for a 24-bp deletion in the SHH gene (600725.0016). His mother, who had unilateral iris and uveoretinal coloboma, and 3 unaffected family members carried the same deletion. The authors noted that incomplete expression of SHH mutations had also been observed in several holoprosencephaly pedigrees (see Nanni et al., 1999).