Foveal Hypoplasia and Anterior Chamber Dysgenesis

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

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. 

Treatment
Treatment Options: 

None known.

References
Article Title: 

A new recessively inherited disorder composed of foveal hypoplasia, optic nerve decussation defects and anterior segment dysgenesis maps to chromosome 16q23.3-24.1

Al-Araimi M, Pal B, Poulter JA, van Genderen MM, Carr I, Cudrnak T, Brown L, Sheridan E, Mohamed MD, Bradbury J, Ali M, Inglehearn CF, Toomes C. A new recessively inherited disorder composed of foveal hypoplasia, optic nerve decussation defects and anterior segment dysgenesis maps to chromosome 16q23.3-24.1. Mol Vis. 2013 Nov 1;19:2165-72. PubMed PMID: 24194637;

PubMed ID: 
24194637

References

Al-Araimi M, Pal B, Poulter JA, van Genderen MM, Carr I, Cudrnak T, Brown L, Sheridan E, Mohamed MD, Bradbury J, Ali M, Inglehearn CF, Toomes C. A new recessively inherited disorder composed of foveal hypoplasia, optic nerve decussation defects and anterior segment dysgenesis maps to chromosome 16q23.3-24.1. Mol Vis. 2013 Nov 1;19:2165-72. PubMed PMID: 24194637;

PubMedID: 24194637

Pal B, Mohamed MD, Keen TJ, Williams GA, Bradbury JA, Sheridan E, Inglehearn CF. A new phenotype of recessively inherited foveal hypoplasia and anterior segment dysgenesis maps to a locus on chromosome 16q23.2-24.2. J Med Genet. 2004 Oct;41(10):772-7.

PubMedID: 15466012

Perez Y, Gradstein L, Flusser H, Markus B, Cohen I, Langer Y, Marcus M, Lifshitz T, Kadir R, Birk OS. Isolated foveal hypoplasia with secondary nystagmus and low vision is associated with a homozygous SLC38A8 mutation. Eur J Hum Genet. 2013 Sep 18.  [Epub ahead of print].

PubMedID: 24045842