Foveal Hypoplasia 1

A number sign (#) is used with this entry because foveal hypoplasia-1 with or without anterior segment anomalies and/or cataract (FVH1) is caused by heterozygous mutation in the PAX6 gene (607108) on chromosome 11p13.

Description

Foveal hypoplasia is defined as the lack of foveal depression with continuity of all neurosensory retinal layers in the presumed foveal area. Foveal hypoplasia as an isolated entity is a rare phenomenon; it is usually described in association with other ocular disorders, such as aniridia (106210), microphthalmia (see 251600), albinism (see 203100), or achromatopsia (see 216900). All reported cases of foveal hypoplasia have been accompanied by decreased visual acuity and nystagmus (summary by Perez et al., 2014).

Genetic Heterogeneity of Foveal Hypoplasia

Foveal hypoplasia-2 (FVH2; 609218) is caused by mutation in the SLC38A8 gene (615585) on chromosome 16q23.

Clinical Features

Curran and Robb (1976) noted that defective development of the fovea usually occurs in patients with aniridia or albinism. However, they reported 9 patients with foveal hypoplasia with varying degrees of congenital nystagmus and poor visual acuity, but no evidence of aniridia or albinism. They suggested that isolated foveal hypoplasia may be more common than previously believed.

Oliver et al. (1987) reported 15 patients with isolated foveal hypoplasia. Characteristic associated findings included poor visual acuity, nystagmus, absent or abnormal maculofoveal reflexes, unclear definition of the maculofoveal area, and capillaries running abnormally close to the presumed macular area. The authors noted that the fundal findings are difficult to detect and also suggested that isolated foveal hypoplasia may be more common than generally believed.

O'Donnell and Pappas (1982) described a family in which 7 persons over 4 generations had mild foveal hypoplasia, presenile cataract (onset before age 40 years), and peripheral corneal pannus. There were 2 instances of male-to-male transmission, suggesting autosomal dominant inheritance. Corneal pannus was described as 'a small peripheral margin of pannus, about 1 mm in width, for 360 degrees.'

Azuma et al. (1996) reported a family in which 5 individuals over 3 generations were affected with isolated foveal hypoplasia. All affected members had poorly defined foveal regions with a normal cornea and iris. In addition, all members had poor visual acuity and nystagmus.

Hanson et al. (1999) reported 3 members in a family who were affected with dominantly inherited congenital nystagmus. In addition, the proband and her mother also had congenital bilateral cataracts, corneal epithelial changes, and foveal hypoplasia. The proband's brother had congenital nystagmus and mild lens opacities. Hanson et al. (1999) suggested that the phenotype in this family resembled the syndrome reported by O'Donnell and Pappas (1982).

Recchia et al. (2002) reported a woman with poor vision and nystagmus who was found to have a 1-mm corneal pannus encompassing the superior 270 degrees of each eye, absent foveal reflexes, and an ill-defined capillary-free zone. Her paternal grandmother, father, and sister reportedly had poor vision, nystagmus, and early cataracts, which Recchia et al. (2002) suggested was most compatible with the syndrome reported by O'Donnell and Pappas (1982). Optical coherence tomography (OCT) showed preservation of multiple inner retinal layers where there should have been none, indicating that the fovea was thicker than normal. The authors suggested that a more accurate term would be 'foveal dysgenesis,' and proposed that OCT might prove helpful in the evaluation of patients with unexplained visual loss.

Inheritance

Male-to-male transmission in the family with foveal hypoplasia reported by O'Donnell and Pappas (1982) suggested autosomal dominant inheritance.

Molecular Genetics

In a family with isolated foveal hypoplasia, Azuma et al. (1996) identified a heterozygous missense mutation in the PAX6 gene (607108.0012) that segregated with the phenotype.

In affected members of a family with foveal hypoplasia and presenile cataracts, Hanson et al. (1999) identified a heterozygous mutation in the PAX6 gene (607108.0014).

In affected members of a family with foveal hypoplasia, congenital nystagmus, and anterior segment anomalies (mainly iris hypoplasia or atypical coloboma), Vincent et al. (2004) identified a heterozygous splice mutation in the PAX6 gene (607108.0021).