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
Inheritance
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. Three additional types of Usher syndrome are recognized: type I (276900) results from mutations in at least 7 different genes, type II (276901) from mutations in 4 genes, and Type IV resulting from mutations in the ARSG gene.
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.