Microphthalmia, Syndromic 4

Clinical Features

In 2 generations of a Northern Ireland family, Graham et al. (1988, 1991) described 7 males with clinical anophthalmia, of whom 3 were deceased at the time of study. The pattern was consistent with X-linked recessive inheritance, and multipoint linkage analysis suggested that gene was localized to the Xq27-q28 region; maximum lod = 1.9 at theta = 0.08. Clinically affected males with bilateral disease had fusion of the eyelid margins (ankyloblepharon) and radiologically demonstrable underdevelopment of the bony orbits. All males had mental retardation (IQ less than 50) and 1 male was born with preauricular skin tags and a cleft soft palate. No deafness was present and lack of limb, hand, dental, and urogenital abnormalities was considered to make Lenz microphthalmia syndrome (309800) unlikely. Although some early reports of 'anophthalmos' were probably instances of Norrie disease (310600), the linkage mapping, if valid, excludes that possibility in this family, since the Norrie disease gene is located at Xp11.4.

Forrester et al. (2001) mapped Lenz microphthalmia syndrome, which has many features similar to those in affected members of the family of Graham et al. (1991), to Xq27-q28.

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.'