WHRN

Usher Syndrome Type II

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 4^th to 5^th 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

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

Treatment

Treatment Options:

Hearing aids can be helpful and speech therapy may be highly beneficial for the development of speech. Cochlear implants have been suggested for older persons who have the more severe hearing loss. Auditory testing should be done shortly after birth and the hearing loss monitored periodically.

An investigational drug (QRX-411) developed by ProQR has been approved as an orphan drug by the FDA and the EMA for patients with the USH2A mutation.

References

Article Title:

Clinical Aspects of Usher Syndrome and the USH2A Gene in a Cohort of 433 Patients

Blanco-Kelly F, Jaijo T, Aller E, Avila-Fernandez A, Lopez-Molina MI, Gimenez A, Garcia-Sandoval B, Millan JM, Ayuso C. Clinical Aspects of Usher Syndrome and the USH2A Gene in a Cohort of 433 Patients. JAMA Ophthalmol. 2014 Nov 6. [Epub ahead of print].

PubMed ID:

25375654

Disease expression in Usher syndrome caused by VLGR1 gene mutation (USH2C) and comparison with USH2A phenotype

Schwartz SB, Aleman TS, Cideciyan AV, Windsor EA, Sumaroka A, Roman AJ, Rane T, Smilko EE, Bennett J, Stone EM, Kimberling WJ, Liu XZ, Jacobson SG. Disease expression in Usher syndrome caused by VLGR1 gene mutation (USH2C) and comparison with USH2A phenotype. Invest Ophthalmol Vis Sci. 2005 Feb;46(2):734-43.

PubMed ID:

15671307

Kinetics of visual field loss in Usher syndrome Type II

Iannaccone A, Kritchevsky SB, Ciccarelli ML, Tedesco SA, Macaluso C, Kimberling WJ, Somes GW. Kinetics of visual field loss in Usher syndrome Type II. Invest Ophthalmol Vis Sci. 2004 Mar;45(3):784-92.

PubMed ID:

14985291

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