Nanophthalmos 1

Description

Autosomal dominant nanophthalmos is characterized by a small eye, as indicated by short axial length, high hyperopia, high lens/eye volume ratio, and a high incidence of angle-closure glaucoma (summary by Othman et al., 1998).

Genetic Heterogeneity of Nanophthalmos

Nanophthalmos-1 (NNO1) has been mapped to chromosome 11p. Nanophthalmos-2 (NNO2; 609549) is caused by mutation in the MFRP gene (606227) on chromosome 11q23. Nanophthalmos-3 (NNO3; 611897) has been mapped to chromosome 2q11-q14. Nanophthalmos-4 (NNO4; 615972) is caused by mutation in the TMEM98 gene (615949) on chromosome 17q11.

Clinical Features

Othman et al. (1998) performed clinical and genetic evaluations of members of a large family with the dominant form of nanophthalmos. Hyperopia ranged from +7.25 to +13.00, with a mean of +9.88 diopters in 22 affected members. Twelve affected members had angle-closure glaucoma or occludable anterior-chamber angles.

After histopathologic examination of sclera resected from a nanophthalmic eye, Yamani et al. (1999) described abnormal collagen fibrils that were frayed, split, and contained lightly stained cores. These abnormal collagen fibrils predominated in the inner sclera or lamina fusca; the scleral stroma and episclera were less abnormal. The authors suggested that the frayed fibrils and glycogen-like deposits they had observed contributed to scleral inelasticity which caused abnormally small intraocular volume and produced choroidal congestion, choroidal detachment, and/or exudative retinal detachment. They reported the successful treatment of a nanophthalmic patient by full-thickness sclerectomies in all 4 quadrants in the eye, resulting in anterior chamber deepening, resolution of the choroidal detachment, and subsequent improvement in visual acuity.

Sener et al. (2003) reported that most of their patients with nanophthalmos also had strabismus. Of their patients with nonaccommodative esotropia who required surgery, they found no need to reduce the surgical dose because of the patients' smaller ocular axial lengths. Of 15 patients studied, 3 had monocular amblyopia; the remaining 12 had binocular amblyopia.

From a study of 8 patients with nanophthalmos, Walsh and Goldberg (2007) concluded that visual deficiency in this disorder may be due to a small, rudimentary foveal avascular zone.

Mapping

By linkage analysis in a family segregating autosomal dominant nanophthalmos, Othman et al. (1998) found linkage of the disorder, which was symbolized NNO1, to chromosome 11 in a 14.7-cM interval. Linked markers were situated on 11p. PAX6 (607108), which is located on chromosome 11p13 and when mutant in the mouse causes 'small-eye,' was thought to be excluded because it is not located within the NNO1 genetic inclusion interval.

Nomenclature

The term 'posterior microphthalmos' (see MCOP6, 613517) was introduced by Franceschetti and Gernet (1965) and later applied to several cases of small eyes with normal-sized anterior segments. Other authors used the designation 'nanophthalmos,' while Warburg, 1993 preferred to label such eyes as 'partial microphthalmos' (summary by Fuchs et al., 2005).