Autosomal recessive isolated posterior microphthalmos defines a rare distinct phenotype restricted to the posterior segment of the eye. In adults, it is clinically characterized by extreme hyperopia (from +7.5 to +21 diopters) due to short axial length (14 ... Autosomal recessive isolated posterior microphthalmos defines a rare distinct phenotype restricted to the posterior segment of the eye. In adults, it is clinically characterized by extreme hyperopia (from +7.5 to +21 diopters) due to short axial length (14 mm to 20 mm; normal is greater than 21 mm). Other features include an essentially normal anterior segment, steep corneal curvatures, shallow anterior chamber, thick lenses, and thickened scleral wall. The palpebral fissures appear narrow because of relatively deep-set eyes, visual acuity is mildly to moderately reduced, and anisometropic or strabismic amblyopia is common. The fundus of the eye shows crowded optical discs, tortuous vessels, and an abnormal foveal avascular zone; in addition, papillomacular folds are often reported. Morphometric features of the small eyes predispose to complications such as narrow-angle glaucoma and uveal effusion (summary by Gal et al., 2011).
Fuchs et al. (2005) reported 2 families from the Faroe Islands, 1 of which had previously been studied by Fledelius and Rosenberg (1987), in which affected individuals exhibited a rare ocular phenotype characterized by a short axial length ... Fuchs et al. (2005) reported 2 families from the Faroe Islands, 1 of which had previously been studied by Fledelius and Rosenberg (1987), in which affected individuals exhibited a rare ocular phenotype characterized by a short axial length (less than 21 mm), mainly confined to the posterior segment of the eye; a shallow anterior chamber; a thickened eye wall; and very high hyperopia (median, +16.5 diopters (D); range, +7.75 D to +22 D). The morphologic characteristics predisposed to sight-threatening complications such as angle-closure glaucoma, chorioretinal pathology including uveal effusion, strabismus, and amblyopia. Fuchs et al. (2005) concluded that endemic high prevalence in the Faroe Islands suggested the presence of a founder effect, and that further genetic research would probably indicate pseudodominant rather than dominant transmission in these families. Hmani-Aifa et al. (2009) studied 6 consanguineous Tunisian families segregating autosomal recessive nonsyndromic posterior microphthalmia. All affected individuals had an identical bilateral phenotype characterized by foreshortening of the eye axial length with normal corneal diameters. Findings in most patients included high hyperopia and an elevated papillomacular retinal fold; other changes included reduction of the capillary-free zone, crowded optic disc, macular pigment migration, and 2 cases of uveal effusion. Two patients developed age-related cataracts. Funduscopy and fluorescein angiography excluded other optic anomalies, and no systemic symptoms were observed in any of the affected individuals. There was no significant inter- or intrafamilial phenotypic variation. Gal et al. (2011) studied a large consanguineous Tunisian family in which 5 of 11 children were affected. Features included nanophthalmos (see 600165) with microcornea, shallow anterior chamber and angle, extreme hyperopia, short axial length, high lens/eye volume ratio, thick sclera and choroid, and absence of overt structural defects. Fundus abnormality was seen in 5 eyes, involving a papillomacular fold in 3 eyes, choroidal neovascular membrane in 1 eye, and a central venous occlusion secondary to angle-closure glaucoma in 1 eye. The authors noted that the phenotype of the Tunisian families reported by Hmani-Aifa et al. (2009) differed from the phenotype in this family with respect to normal corneal diameters and steepness in the former. In addition, Gal et al. (2011) studied 4 Faroese patients from 2 large pedigrees, 1 originally reported by Fledelius and Rosenberg (1987) and 1 previously studied by Fuchs et al. (2005), and 23 sporadic Faroese patients, all of whom had a phenotype that was very similar to that of their Tunisian family except for having corneal diameters that were in the lower range of normal. Gal et al. (2011) suggested that a distinction between posterior microphthalmos and nanophthalmos might be artificial, and that the 2 conditions might represent a continuum of phenotypes. Nair et al. (2011) restudied the 6 Tunisian families originally reported by Hmani-Aifa et al. (2009), including 25 patients with posterior microphthalmia and 88 unaffected relatives. They observed that 4 affected individuals from 2 of the families (PM2 and PM3) had elevated intraocular pressure, with levels ranging from 26 mmHg to 30 mmHg. In addition, 2 affected individuals from another family (PM1) displayed optic nerve excavation.
In a large consanguineous Tunisian family segregating autosomal recessive posterior microphthalmos, Gal et al. (2011) analyzed the candidate gene PRSS56 (613858) and identified a homozygous 1-bp duplication that segregated with the disease (613858.0001). Analysis of PRSS56 in 27 ... In a large consanguineous Tunisian family segregating autosomal recessive posterior microphthalmos, Gal et al. (2011) analyzed the candidate gene PRSS56 (613858) and identified a homozygous 1-bp duplication that segregated with the disease (613858.0001). Analysis of PRSS56 in 27 Faroese patients from 25 families revealed that all but 1 patient were homozygous or compound heterozygous for 2 mutations, W309S (613858.0002) and R176G (613858.0003), respectively. None of the mutations was found in 100 German controls, but 3 of 94 Faroese controls were heterozygous for W309S, corresponding to a heterozygote frequency of 3.2%. Genealogic studies identified a married couple from the 1600s as ancestors of the parents of all affected Faroese individuals carrying W309S in homozygous or heterozygous state. No PRSS56 mutation was detected in 1 patient from the Faroe Islands or in 1 patient from Turkey, suggesting genetic heterogeneity for posterior microphthalmia. In 6 Tunisian families with posterior microphthalmia mapping to chromosome 2q37, originally reported by Hmani-Aifa et al. (2009), Nair et al. (2011) screened 18 candidate genes and identified homozygosity for a 1-bp insertion in the PRSS56 gene (1066insC; 613858.0001) in 5 of the 6 families. In the sixth family (PM6), they identified homozygosity for a missense mutation in PRSS56 (P599A; 613858.0004). Neither mutation was found in population-matched controls.