hypermetropia

Leber Congenital Amaurosis with Early-Onset Deafness

Clinical Characteristics
Ocular Features: 

Evidence for retinal disease can be seen within 3 years of age.  Three of 5 patients had no detectable responses on the ERG when tested at birth.  A 34-year-old female was noted to have advanced retinitis pigmentosa with attenuation of retinal vessels, choroidal atrophy, peripheral pigmentary deposits, and macular anomalies.  The posterior fundus may have a salt-and-pepper pigmentation.  Hypermetropia was present in all 5 patients.

Visual acuity varies widely and may be normal even among older patients.

Systemic Features: 

Mild to severe sensorineural hearing loss secondary to cochlear cell loss is usually diagnosed in the first decade.  All patients had normal neuro-psychomotor development.

Genetics

Heterozygous mutations in the TUBB4B gene (9q34.3) have been found in 5 individuals in 4 families with this disorder.  There may be significant mosaicism in blood cells.

See Leber Congenital Amaurosis for additional information on non-syndromal Leber congenital amaurosis and responsible mutations.

Pedigree: 
Autosomal dominant
Treatment
Treatment Options: 

No treatment is available for the general condition but refractive correction, low vision aids, and assistive hearing devices may be of benefit.

References
Article Title: 

Mutations in TUBB4B Cause a Distinctive Sensorineural Disease

Luscan R, Mechaussier S, Paul A, Tian G, Gerard X, Defoort-Dellhemmes S, Loundon N, Audo I, Bonnin S, LeGargasson JF, Dumont J, Goudin N, Garfa-Traore M, Bras M, Pouliet A, Bessieres B, Boddaert N, Sahel JA, Lyonnet S, Kaplan J, Cowan NJ, Rozet JM, Marlin S, Perrault I. Mutations in TUBB4B Cause a Distinctive Sensorineural Disease. Am J Hum Genet. 2017 Dec 7;101(6):1006-1012.

PubMed ID: 
29198720

Albinism, Ocular Type 1

Clinical Characteristics
Ocular Features: 

Signs in ocular albinism include hypopigmentation of the fundus with clearly visible choroidal vessels, foveal hypoplasia, and hypopigmentation of the iris. Strabismus, nystagmus, photophobia, absent stereoacuity and high refractive errors including hypermetropia are other common features.  Vision may be near normal but usually worse, in the range of 20/100 to 20/300.  In at least some patients with ocular albinism, concentric macular rings have been identified using infrared reflectance images.

In ocular albinism there is a nearly complete crossing of nerve fibers in the optic chiasm as well as a decreased number of photoreceptors.  MRI imaging of the optic chiasm in humans with albinism reveals it to be smaller with a wider angle between optic tracts, reflecting the atypical crossing of nerve fibers.

This is an X-linked recessive disorder and affects mainly men. In 80% of female carriers a mosaic of pigmentary changes can be observed in the fundus, especially in the periphery as a result of lyonization.  A few female heterozygotes have ocular changes of albinism including nystagmus and reduced visual acuity, likely as a result of unequal X-chromosome inactivation.  Perhaps three-quarters of carrier females have transillumination defects in the iris.

Hearing loss is often associated with pigmentation disorders and one large family with X-linked ocular albinism has been reported with a late onset sensorineural deafness (300650).  The ocular findings are typical but deafness is not significant until late midlife.

Systemic Features: 

In ocular albinism, pigmentation is normal except in the eye.  Hearing loss has been reported in a single family but this may be a unique disorder since the genotype was not determined.

Genetics

Ocular albinism (OA1) is a recessive X-linked disorder, caused by mutations in the GPR143 gene, located at Xp22.3.  The protein product, a G protein-coupled receptor, is localized on the membrane of melanosomes in pigmented cells in the eye.  The same gene is mutated in congenital nystagmus 6 (300814).  Ocular albinism with late onset sensorineural deafness (300650) results from mutations in the Xp22.3 region as well and may or may not be the same condition.

It has been reported that mutations in GNA13 (17q24.1), activated by OA1, can also result in the ocular albinism phenotype.

Pedigree: 
X-linked recessive, carrier mother
X-linked recessive, father affected
Treatment
Treatment Options: 

Treatment for the ocular symptoms is targeted toward specific problems. Refractive errors are treated with corrective glasses with tinted lenses recommended for the photophobia. Low vision aids and special education may be required.

References
Article Title: 
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