Usher Syndrome [H54.9] and [H91.9]
Dr. rer. biol. hum. S. Chahrokh-Zadeh
Usher syndrome (USH), a group of clinically and genetically heterogeneous, autosomal recessive diseases with bilateral sensorineural hearing loss, in part with vestibular dysfunction and gradual retinal degeneration, retinitis pigmentosa (RP), is the main cause (> 50%) of deaf-blindness. Prevalence is estimated to be 1 in 6,000. Three main subtypes USH1, USH2 and USH3 are mainly distinguished by the severity and progression of deafness and presence of the vestibular defects. So far 12 genes and one modifier gene (PDZD7) have been identified.
Usher syndrome type 1 (USH1) represents 30-40% of all USH types and constitutes the most severe form with high grade congenital deafness, onset of visual impairment (RP) before puberty and frequently vestibular dysfunction. Patients with USH1 are often only diagnosed with hearing loss until the reduced field of vision (tunnel vision) and night blindness (first signs of RP) have progressed so far that they become evident. However, an early diagnosis is important for adequate schooling and support in childhood. Classification of the single subtypes based on clinical data is insufficient as there is high phenotypic variability even if identical mutations are present. So far 9 loci and 6 genes are known: MYO7A (USH1B; 53%-63% of all USH1), USH1C (USH1C; 1%-15%), CDH23 (USH1D; 7%-20%), PCDH15 (USH1F; 7%-12%), USH1G (USH1G) and CIB2 (USH1J).
The most common subtype involves USH2 (moderate to severe hearing loss, RP rather after puberty, and normal vestibular function). Most of the mutations can be detected in the USH2A gene (USH2A; 57%-79%).
Mutations in the above mentioned genes are also described in patients with autosomal recessive, non-syndromic, congenital or prelingual deafness, e.g. MYO7A in DFNA11 (autosomal dominant) and DFNB2 (autosomal recessive), CDH23 in DFNB12 and PCDH15 in DFNB23. Digenic inheritance, each with a mutation in one of the affected genes e.g. CDH23 and PCDH15 is also known. Autosomal recessive, non-syndromic, congenital or prelingual deafness is genetically heterogeneous, with to date up to 50 known genes and approximately 25 loci.