lipofuscin accumulation

Macular Dystrophy, Vitelliform 5

Clinical Characteristics
Ocular Features: 

This is a late onset form of vitelliform macular dystrophy with symptoms noted by the 5th decade or later.  Only central vision seems to be impacted and a central scotoma may be demonstrable.  The ERG, EOG and color vision responses may be normal.  Mild autofluorescence has been reported.  The vitelliform lesions are small and may be multiple.  No drusen-like lesions have been seen.  Visual acuity is variable, ranging from normal to a mild decrease. 

Systemic Features: 

No systemic abnormalities have been reported.

Genetics

This form of vitelliform dystrophy results from heterozygous mutations in the IMPG2 gene (3q12).  Patients with homozygous mutations have also been reported.

Genotyping has identified at least 5 forms of vitelliform macular dystrophy.  In addition to the iconic Best disease (VMD2, 153700) apparently first described by Friedreich Best in 1905 and now attributed to mutations in the Best1 gene, we know of at least 4 more and specific mutations have been identified in three.  No mutation or locus has yet been identified in VMD1 (153840) but it is likely a unique condition since mutations in other genes known to cause vitelliform dystrophy have been ruled out.  Other forms are VMD3 (608161) due to mutations in the PRPH2 gene, VMD4 (616151) resulting from mutations in the IMPG1 gene, and VMD5 described here.

Pedigree: 
Autosomal dominant
Autosomal recessive
Treatment
Treatment Options: 

No treatment is known for the macular dystrophy.  Low vision devices might be helpful for selected individuals.

References
Article Title: 

Mutations in IMPG2, encoding interphotoreceptor matrix proteoglycan 2, cause autosomal-recessive retinitis pigmentosa

Bandah-Rozenfeld D, Collin RW, Banin E, van den Born LI, Coene KL, Siemiatkowska AM, Zelinger L, Khan MI, Lefeber DJ, Erdinest I, Testa F, Simonelli F, Voesenek K, Blokland EA, Strom TM, Klaver CC, Qamar R, Banfi S, Cremers FP, Sharon D, den Hollander AI. Mutations in IMPG2, encoding interphotoreceptor matrix proteoglycan 2, cause autosomal-recessive retinitis pigmentosa. Am J Hum Genet. 2010 Aug 13;87(2):199-208.

PubMed ID: 
20673862

Macular Dystrophy, Vitelliform 1

Clinical Characteristics
Ocular Features: 

This is an uncommon form of vitelliform macular dystrophy and may not be a unique disorder.  Onset of disease is usually later than in the classic Best disease due to mutations in the Best1 gene.  Only slight to moderate vision impairment is present. Small drusen-like lesions may be seen in the foveal areas along with macular or extramacular punctate yellow lesions.  Importantly, the EOG light/dark Arden ratio is often normal or only slightly impacted even when severe loss of vision is present.  It has been claimed that fundus fluorescein angiography is diagnostically more reliable than the EOG.  Patchy RPE depigmentation is often present in the central and the peripheral retina as well as in the peripapillary area.

The clinical features resemble vitelliform macular dystrophy resulting from mutations in the IMPG1 and IMPG2 genes. 

Systemic Features: 

No systemic abnormalities have been reported.

Genetics

No mutation or locus has been found to segregate with VMD1 disease.  However, it is probably a unique condition since other VMD-causing mutations such as those in Best1, PRPH2, IMPG1, and IMPG2 have been ruled out in a number of families.

The transmission pattern is consistent with autosomal dominant inheritance.

Genotyping has identified at least 5 forms of vitelliform macular dystrophy.  In addition to the iconic Best disease (VMD2, 153700) apparently first described by Friedreich Best in 1905 and now attributed to mutations in the Best1 gene, we know of at least 4 more and specific mutations have been identified in three.  Other forms are VMD3 (608161) due to mutations in the PRPH2 gene, VMD4 (616151) resulting from mutations in the IMPG1 gene, and VMD5 (616152) caused by mutations in the IMPG2 gene.

Pedigree: 
Autosomal dominant
Treatment
Treatment Options: 

No treatment is available for this disease but low vision devices may be helpful.

References
Article Title: 
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