SLC38A8

Foveal Hypoplasia 2

Clinical Characteristics
Ocular Features: 

The cardinal feature in this condition is foveal hypoplasia which is characterized by the lack of a foveal depression and continuity of all neurosensory layers across the foveal area as revealed by OCT.  This is accompanied by poor visual acuity, nystagmus, and strabismus.  Hypopigmentation of the immediate area has also been reported in some patients.  Visual acuity in one study of 9 patients ranged from 20/50 to 20/200.  The ERG and flash VEP can be normal.  Color vision has been described as normal in some individuals.

Dysgenesis of the anterior segment seems to be family-specific and consists of Axenfeld anomaly or embryotoxon.

Systemic Features: 

In most cases the only features are foveal hypoplasia with or without anterior chamber anomalies.  Three affected sisters in one family were reported to have mild developmental delay.

Genetics

Homozygous mutations in SLC38A8 (16q23.3) are responsible for this disorder. 

For a somewhat similar condition of foveal hypoplasia see FVH1 (136520), which is, however, caused by a different mutation and inherited in an autosomal dominant pattern.

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

There is no known treatment.

References
Article Title: 

Foveal Hypoplasia 1

Clinical Characteristics
Ocular Features: 

This is a poorly defined syndrome with features overlapping aniridia, hereditary keratitis, ocular albinism, and iris anomalies as in Peters anomaly.  However, presenile cataracts seem to be unique to this disorder.  The foveal hypoplasia may occur without other anomalies although the fundus is usually lightly pigmented.  As expected, acuity is subnormal from birth, in the range of 20/50, and dyschromatopsia may be present.  Some patients have nystagmus.  Weak iris transillumination has been reported and a small limbal pannus may be present. Lens opacities may become visually significant in the third to fourth decade of life.  OCT has shown abnormal foveal thickness with multiple inner retinal layers somewhat similar to the situation in oculocutaneous albinism (203100) and it has been suggested that 'foveal dysplasia' is a better description than 'foveal hypoplasia'. 

Systemic Features: 

No systemic disease is present. 

Genetics

This disorder is associated with mutations in the PAX6 gene (11p13) and inherited as an autosomal dominant.

The protein product of the PAX6 gene is a transcription factor that attaches to DNA and regulates the expression of other genes.  PAX6 plays a major role primarily in development of the eye and central nervous system but evidence suggests it is also active postnatally.  Hundreds of mutations have been found in disorders such as hereditary keratitis, aniridia, Peters anomaly, hypoplasia and colobomas of the optic nerve.  This database contains 8 conditions in which mutations in PAX6 seem to be responsible, including syndromal conditions such as Stromme and Gillespie syndromes in which there may be cognitive disabilities. 

True isolated foveal hypoplasia without lens or corneal disease does exist as well but this condition (FVH2) is not well defined.  Homozygous mutations in SLC38A8 have been found to cosegregate with this form of foveal hypoplasia among families of Jewish Indian ancestry.  Hypopigmentation is not a feature of isolated foveal hypoplasia secondary to such mutations but misrouting of optic nerve axons may be present.  Nystagmus and reduced vision but no anterior segment abnormalities were present.

With the widespread utilization of OCT measurements, we have learned 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 foveal hypoplasia with anterior segment dysgenesis (609218).

 

Pedigree: 
Autosomal dominant
Treatment
Treatment Options: 

Cataract surgery is indicated when lens opacities become visually significant. 

References
Article Title: 

Recessive Mutations in SLC38A8 Cause Foveal Hypoplasia and Optic Nerve Misrouting without Albinism

Poulter JA, Al-Araimi M, Conte I, van Genderen MM, Sheridan E, Carr IM, Parry DA, Shires M, Carrella S, Bradbury J, Khan K, Lakeman P, Sergouniotis PI, Webster AR, Moore AT, Pal B, Mohamed MD, Venkataramana A, Ramprasad V, Shetty R, Saktivel M, Kumaramanickavel G, Tan A, Mackey DA, Hewitt AW, Banfi S, Ali M, Inglehearn CF, Toomes C. Recessive Mutations in SLC38A8 Cause Foveal Hypoplasia and Optic Nerve Misrouting without Albinism. Am J Hum Genet. 2013 Dec 5;93(6):1143-50.

PubMed ID: 
24290379
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