OMIM ID:
Foveal Hypoplasia and Anterior Chamber Dysgenesis
Alternate Names
Defective Genes
Clinical Characteristics
Ocular Features
This is a congenital disorder with poor vision (20/120-20/400) and nystagmus from birth according to family history. Three of five patients in one family had a posterior embryotoxon and two had Axenfeld anomaly. No glaucoma was present although no individuals were older than 15 years of age at the time of examination. The foveal reflex was absent and there was a poorly defined foveal avascular zone with no distinction of the foveomacular area. Reduced ERG amplitudes and similar VEP responses were found in 4 affected individuals but these recordings were normal in the parents. Chiasmal misrouting has been reported in two affected members of one family. The combination of foveal hypoplasia and decussation defects is characteristic of disorders of pigmentation (albinism) but no iris defects or other evidence of pigmentary anomalies have been found in this condition of foveal hypoplasia.
Systemic Features
No systemic abnormalities were described.
Genetics
Inheritance
Consanguinity has been reported. A region containing 33 genes at 16q23.2-24.2 co-segregates with the disorder but no mutation has been identified. Mutations in FOXC2 and PAX6 (that code for transcription factors) have been specifically ruled out in selected families. However, the phenotype is consistent with dysfunction of some other as yet unidentified transcription control factor or promotor region.
An autosomal dominant disorder with somewhat similar features known as anterior segment mesenchymal dysgenesis (107250) has been described but its unique status remains to be established. Foveal hypoplasia has not been reported but an associated mutation in FOXE3 could be responsible.
Isolated foveal hypoplasia without anterior chamber malformations (136520) has been reported among families of Jewish Indian ancestry in which homozygous mutations SLC38A8 cosegregated.
With the widespread utilization of OCT measurements, it has become apparent that underdevelopment of the fovea can be a feature of numerous ocular disorders (more than 20 in this database). In most conditions, the foveal dysplasia is part of a disease complex as in this condition.
Pedigree
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.