Microphthalmia, Syndromic 13

A number sign (#) is used with this entry because of evidence that syndromic microphthalmia-13 (MCOPS13) is caused by mutation in the HMGB3 gene (300193) on chromosome Xq28. One such family has been reported.

Clinical Features

Goldberg and McKusick (1971) reported a nonconsanguineous kindred in which 4 males in 3 sibships connected through females had colobomatous microphthalmia, microcephaly, short stature, and psychomotor retardation. Additional features included ptosis, pendular nystagmus, esotropia, simple and anteverted ears, and diastema of the incisors. Corneal measurements ranged from 3 to 6 mm in diameter; posterior segment examination in the proband and another affected individual revealed that their iris colobomas extended through the retina and choroid to the ciliary body, and involved the optic nerve in the proband. One patient exhibited severe kyphoscoliosis. There were no instances of male-to-male transmission. Two female members of the pedigree, who could not be examined, were said to have eye anomalies and possibly represented manifesting heterozygotes. Because the kindred resided along the eastern coast of Maine, Goldberg and McKusick (1971) suggested the designation 'Maine microphthalmos' for the disorder.

The X-linked disorder described by Siber (1984) had many features similar to those described in the Goldberg and McKusick (1971) report.

Inheritance

The transmission pattern of a microphthalmia syndrome in the family reported by Goldberg and McKusick (1971) suggested X-linked inheritance.

Molecular Genetics

In an affected man from the family with syndromic microphthalmia originally reported by Goldberg and McKusick (1971), Scott et al. (2014) performed exome sequencing and identified a 2-bp insertion in the HMGB3 gene (300193.0001) that was confirmed by Sanger sequencing in the patient and his unaffected mother. Analysis of HMGB3 in 13 unrelated male patients with microphthalmia syndromes revealed no further mutations.