OMIM ID:
Macular Dystrophy, Vitelliform 4
Alternate Names
Defective Genes
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
Inheritance
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.
Pedigree
Autosomal dominant
Autosomal dominant disorders require only one mutation for the disease to be expressed. Since an affected parent has two chromosomes, only one of which has the mutant gene, parents can expect that half (50%) of their children will receive that one and inherit the disease. It is common for individuals that inherit the mutation, however, to not have evidence of the disease (nonpenetrance).
Autosomal dominant inheritance leads to a vertical pattern of transmission
Autosomal recessive
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.