Clinical Characteristics
Ocular Features
Retinitis pigmentosa is clinically similar to that of nonsyndromal RP and produces symptoms of nightblindness by adolescence. The ERG is severely reduced and visual fields are constricted. Rods seem to be more severely affected than cones. A loss of thickness in the outer nuclear layer in USH2C and USH2A types has been described. The fundus often contains patches of hyperfluorescence which become larger and often coalesce in older patients. The retinal disease is progressive but more slowly than in type I. Eventually by the 4th to 5th decades the visual field is constricted to 5-10 degrees. It can result in blindness. Cataracts are common and some patients have cystic changes in the macula.
Systemic Features
The hearing deficit in type II can be described as hearing loss rather than deafness as found in type I. Usually high frequencies are impacted more severely than lower frequencies producing a characteristic ‘sloping’ audiogram. The hearing loss is present at birth and progressive, at least in some individuals. Speech usually develops. Vestibular dysfunction is not a feature of type II Usher syndrome. The mental changes observed in type I do not occur in type II.
Genetics
Inheritance
Like other forms of Usher syndrome, type II is inherited in an autosomal recessive pattern. Like type I, it is genetically heterogeneous and mutations in at least 4 genes seem to be responsible. Three have been identified: type IIA (USH2A; 276901) results from mutations in the USH2A gene on chromosome 4 (1q41), type IIC (USH2D; 605472) from mutations in GPR98 (5q14), and type IID (USH2D; 611383) is caused by mutations in the DFNB31 gene (9q32-q34). Type IIB (USH2B) results from mutations in a locus mapped to 3p24.2-p23 but the gene has not been identified. Clinical features are sufficiently similar so that these are discussed here as a single entity.
This is the most common of the three types of Usher syndrome. Type I Usher syndrome (276900) results from mutations in at least 7 genes and type III (276902) is caused by a mutations in the CLRN1 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.