Microphthalmia, Isolated 2

A number sign (#) is used with this entry because isolated microphthalmia-2 (MCOP2) is caused by homozygous mutation in the CHX10 gene (142993) on chromosome 14q24.

For a phenotypic description and a discussion of genetic heterogeneity of isolated microphthalmia, see MCOP1 (251600).

Nomenclature

The term 'anophthalmia' has been misused in the medical literature. True or primary anophthalmia is rarely compatible with life; in such cases, the primary optic vesicle has stopped developing and the abnormal development involves major defects in the brain as well (Francois, 1961). The diagnosis can only be made histologically (Reddy et al., 2003; Morini et al., 2005; Smartt et al., 2005), but this is rarely done. In most published cases, the term 'anophthalmia' is used as a synonym for the more appropriate terms 'extreme microphthalmia' or 'clinical anophthalmia.'

Clinical Features

Kohn et al. (1988) described a large consanguineous Arab kindred in Israel in which 19 persons over 3 generations had bilateral profound microphthalmia without associated anomalies and with normal intelligence. One female infant had tracheoesophageal fistula repaired in the neonatal period; when examined at 1 month of age, she had mild right hydronephrosis by intravenous pyelography and ultrasound. Kohn et al. (1988) stated that these abnormalities were 'undoubtedly unrelated to the microphthalmia' (see microphthalmia and esophageal atresia, MCOPS3, 206900).

Molecular Genetics

Bar-Yosef et al. (2004) studied 4 families (2 of Arab origin, 1 of Bedouin origin, and 1 of Persian Jewish origin) with autosomal recessive isolated microphthalmia/clinical anophthalmia and no associated eye anomalies. In the 2 Arab families, 1 of which had previously been reported by Kohn et al. (1988), they identified homozygosity for a missense mutation (142993.0003) and a deletion (142993.0004) in the CHX10 gene, respectively. No mutations were identified in the other 2 families.

In 6 affected individuals from 2 consanguineous families from Qatar with isolated microphthalmia and cloudy corneas, Faiyaz-Ul-Haque et al. (2007) identified homozygosity for an R200P mutation (142993.0002) in the CHX10 gene. Craniofacial features, height, weight, and intelligence were normal in these patients. Unaffected parents were heterozygous for the mutation.