Usher Syndrome Type III

Clinical Characteristics
Ocular Features: 

Retinitis pigmentosa is a cardinal feature with onset of severe symptoms of nightblindness and tunnel vision by the second decade of life.  The ERG shows depressed responses.  Central vision may also be lost in young adults.  Hypermetropic astigmatism has been reported as the most typical refractive error for type III in the presence of nightblindness and hearing loss, at least in Finnish patients.

Systemic Features: 

Hearing loss is progressive but later in onset than in type I and type II.  Infants are usually born with normal hearing and often experience some loss of hearing by the end of the first decade of life.  Speech can develop normally because of the late onset of the hearing deficit.  Hearing loss is progressive early with older patients having a profound and eventually more stable hearing deficit.  The amount of vestibular dysfunction is variable but usually is severe enough to cause significant unsteadiness.  The mental changes associated with type I are absent.

Genetics

Usher syndrome is a clinically and genetically heterogeneous condition.   Type IIIA is caused by a mutation in the CLRN1 gene (3q21-q25).  It is inherited in an autosomal recessive pattern.  Type IIIB (614505) is the result of homozygous mutations in HARS (5q31.3).

There is also a disorder resembling Usher that results from homozygous mutations in ABHD12 (20p11.21) that also causes PHARC (612674) (polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and early onset cataract).

This is the least common type of Usher syndrome.  Two additional types of Usher syndrome are recognized:  type I (276900) results from mutations in at least 7 different genes, and type II (276901) from mutations in 4 genes.

Treatment
Treatment Options: 

Hearing aids might be helpful early but cochlear implants may be needed in older patients with severe deafness.  Low vision aids are often helpful.

References
Article Title: 

Targeted next-generation sequencing identifies a homozygous nonsense mutation in ABHD12, the gene underlying PHARC, in a family clinically diagnosed with Usher syndrome type 3

Eisenberger T, Slim R, Mansour A, Nauck M, N?ornberg G, N?ornberg P, Decker C, Dafinger C, Ebermann I, Bergmann C, Bolz HJ. Targeted next-generation sequencing identifies a homozygous nonsense mutation in ABHD12, the gene underlying PHARC, in a family clinically diagnosed with Usher syndrome type 3. Orphanet J Rare Dis. 2012 Sep 2;7(1):59. [Epub ahead of print]

PubMed ID: 
22938382

References

Eisenberger T, Slim R, Mansour A, Nauck M, N?ornberg G, N?ornberg P, Decker C, Dafinger C, Ebermann I, Bergmann C, Bolz HJ. Targeted next-generation sequencing identifies a homozygous nonsense mutation in ABHD12, the gene underlying PHARC, in a family clinically diagnosed with Usher syndrome type 3. Orphanet J Rare Dis. 2012 Sep 2;7(1):59. [Epub ahead of print]

PubMedID: 22938382

Geng R, Geller SF, Hayashi T, Ray CA, Reh TA, Bermingham-McDonogh O, Jones SM, Wright CG, Melki S, Imanishi Y, Palczewski K, Alagramam KN, Flannery JG. Usher syndrome IIIA gene clarin-1 is essential for hair cell function and associated neural activation. Hum Mol Genet. 2009 Aug 1;18(15):2748-60. Epub 2009 May 3.

PubMedID: 19414487

Aller E, Jaijo T, Oltra S, Ali?? J, Gal?degn F, N?degjera C, Beneyto M, Mill?degn JM. Mutation screening of USH3 gene (clarin-1) in Spanish patients with Usher syndrome: low prevalence and phenotypic variability. Clin Genet. 2004 Dec;66(6):525-9.

PubMedID: 15521980

Pakarinen L, Tuppurainen K, Laippala P, M?SSntyj?SSrvi M, Puhakka H. The ophthalmological course of Usher syndrome type III. Int Ophthalmol. 1995-1996;19(5):307-11.

PubMedID: 8864816