Macular Dystrophy, Vitelliform 4

Clinical Characteristics
Ocular Features: 

This is a late onset form of vitelliform dystrophy in which symptoms are usually noted between the ages of 20 to 45 years.  The vitelliform lesions usually occur singly and are often small.  Some individuals have small drusen-like macular lesions adjacent to the vitelliform lesions, at the periphery of the macula, or even outside the macula.  The lesions contain lipofuscin which can be seen on autofluorescence photographs.  Visual acuity can remain near normal for many years.  The EOG ratio and ERG responses are usually normal or near normal.  Choroidal neovascularization has not been described. 

Systemic Features: 

There are no systemic manifestations.

Genetics

This form of vitelliform dystrophy (VMD4) is caused by heterozygous mutations in the IMPG1 gene (6q14.1).  However, rare families have been reported in which compound heterozygous or homozygous mutations have been found.  Some of the heterozygous parents of children with two mutations were found to have minor fundus changes such as tiny extramacular vitelliform spots in spite of being asymptomatic. This suggests that the transmission pattern of fundus changes may be both autosomal recessive and autosomal dominant. 

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 described here, and VMD5 (616152) caused by mutations in the IMPG2 gene.

Treatment
Treatment Options: 

No treatment is available for the vitelliform disease but low vision devices can be helpful in some patients for selected tasks.

References
Article Title: 

Mutations in IMPG1 cause vitelliform macular dystrophies

Manes G, Meunier I, Avila-Fernandez A, Banfi S, Le Meur G, Zanlonghi X, Corton M, Simonelli F, Brabet P, Labesse G, Audo I, Mohand-Said S, Zeitz C, Sahel JA, Weber M, Dollfus H, Dhaenens CM, Allorge D, De Baere E, Koenekoop RK, Kohl S, Cremers FP, Hollyfield JG, Senechal A, Hebrard M, Bocquet B, Ayuso Garcia C, Hamel CP. Mutations in IMPG1 cause vitelliform macular dystrophies. Am J Hum Genet. 2013 Sep 5;93(3):571-8.

PubMed ID: 
23993198

References

Meunier I, Manes G, Bocquet B, Marquette V, Baudoin C, Puech B, Defoort-Dhellemmes S, Audo I, Verdet R, Arndt C, Zanlonghi X, Le Meur G, Dhaenens CM, Hamel CP. Frequency and Clinical Pattern of Vitelliform Macular Dystrophy Caused by Mutations of Interphotoreceptor Matrix IMPG1 and IMPG2 Genes. Ophthalmology. 2014 Dec;121(12):2406-14.

PubMedID: 25085631

Manes G, Meunier I, Avila-Fernandez A, Banfi S, Le Meur G, Zanlonghi X, Corton M, Simonelli F, Brabet P, Labesse G, Audo I, Mohand-Said S, Zeitz C, Sahel JA, Weber M, Dollfus H, Dhaenens CM, Allorge D, De Baere E, Koenekoop RK, Kohl S, Cremers FP, Hollyfield JG, Senechal A, Hebrard M, Bocquet B, Ayuso Garcia C, Hamel CP. Mutations in IMPG1 cause vitelliform macular dystrophies. Am J Hum Genet. 2013 Sep 5;93(3):571-8.

PubMedID: 23993198