Macular Dystrophy, Vitelliform, 5

A number sign (#) is used with this entry because of evidence that vitelliform macular dystrophy-5 (VMD5) is caused by heterozygous mutation in the IMPG2 gene (607056) on chromosome 3q12.

Description

Macular dystrophies are inherited retinal dystrophies in which various forms of deposits, pigmentary changes, and atrophic lesions are observed in the macula lutea, the cone-rich region of the central retina. Vitelliform macular dystrophies (VMDs) form a subset of macular dystrophies characterized by round yellow deposits, usually at the center of the macula and containing lipofuscin, a chemically heterogeneous pigment visualized by autofluorescence imaging of the fundus (summary by Manes et al., 2013). Vitelliform macular dystrophy-5 is characterized by late-onset moderate visual impairment, preservation of retinal pigment epithelium (RPE) reflectivity, deposits above the RPE between the ellipsoid and outer segment interdigitation lines on spectral-domain optical coherence tomography (SD-OCT), and normal or borderline results on electrooculopathy (EOG) (Meunier et al., 2014).

For a discussion of genetic heterogeneity of vitelliform macular dystrophy, see VMD1 (153840).

Clinical Features

Bandah-Rozenfeld et al. (2010) examined an Israeli Christian Arab woman, born of first-cousin parents, who was diagnosed with mild maculopathy at 63 years of age. She had mild nuclear sclerosis of the lens, and visual field testing showed a relative central scotoma in the right eye with a normal visual field on the left. Full-field electroretinography (ERG) responses were within normal limits, and color vision was normal. OCT revealed elevation of the photoreceptor layer in the foveal region.

Meunier et al. (2014) reported a father and son with vitelliform macular dystrophy. The 44-year-old father reported moderate loss of vision in the right eye. A small vitelliform macular lesion which exhibited mild autofluorescence was noted in both eyes. There were no associated drusen-like lesions in the foveal zone. Spectral-domain optical coherence tomography (SD-OCT) showed disruption of the ellipsoid line with material deposited above the RPE, which showed normal hyperreflectivity. The asymptomatic 22-year-old son had normal findings on funduscopy, but SD-OCT showed an abnormally thin reflective line between the ellipsoid and outer segment-RPE interdigitation lines. The Arden ratio on EOG was normal in both patients.

Molecular Genetics

In a father and son with vitelliform macular dystrophy, who were negative for mutation in the BEST1 (607854), PRPH2 (179605), and IMPG1 (602870) genes, Meunier et al. (2014) identified heterozygosity for a missense mutation in the IMPG2 gene (C1077F; 607056.0002). The father's affected sister was also heterozygous for the mutation, which was not found in an unaffected daughter, in 57 ophthalmologically unaffected and ethnically matched controls with no personal or family history of macular degeneration or retinal dystrophy, or in public SNP databases. Meunier et al. (2014) noted that homozygosity for a missense mutation in IMPG2 (F124L; 607056.0005) had previously been identified by Bandah-Rozenfeld et al. (2010) in a patient with mild maculopathy, which Meunier et al. (2014) designated as representing 'a case of autosomal recessive macular vitelliform dystrophy.'