HEREDITARY HEARING LOSS: USHER SYNDROME Usher syndrome is a clinically and genetically heterogeneous autosomal recessive disorder For More Information characterized by sensorineural hearing deficiencies at birth and later development of progressive retinitis pigmentosa (RP). RP is progressive, bilateral, symmetric retinal GeneReviews: Usher syndrome degeneration that begins with night blindness and constricted visual fields (tunnel vision) and type I: http:// eventually includes decreased central visual acuity .There are 3 types of Usher syndrome; www.ncbi.nlm.nih.gov/books/ these types are distinguished by their severity and the age when signs and symptoms NBK1265/ appear. Individuals with Usher syndrome type I are typically born completely deaf or lose Usher syndrome type II: http:// most of their hearing within the first year of life. Progressive vision loss caused by RP www.ncbi.nlm.nih.gov/books/ becomes apparent in childhood. Usher syndrome type II is characterized by hearing loss from NBK1341/ birth and progressive vision loss that begins in adolescence or adulthood. The hearing loss occurs predominantly in the higher frequencies and ranging from mild to severe . Unlike other Genome Diagnostics forms of Usher syndrome, people with type II do not have difficulties with balance caused by Laboratory: www.sickkids.ca/ inner ear problems. Individuals with Usher syndrome type III experience progressive hearing genome-diagnostics loss and vision loss beginning in the first few decades of life. Hearing loss typically begins To locate a genetics center during late childhood or adolescence, after the development of speech, and progresses over near you: time. By middle age, most affected individuals are profoundly deaf. Vision loss caused by RP Canadian Association of Genetic also develops in late childhood or adolescence. Individuals may also experience difficulties Counsellors (CAGC): www.cagc- with balance due to inner ear problems. accg.ca GENETICS TEST METHODS National Society of Genetic Counselors (NSGC): All three types of Usher syndrome are Complete sequencing of the coding region www.nsgc.org inherited in an autosomal recessive manner. and flanking intron/exon boundaries of the A subset of patients have a digenic forms of genes listed below. This is done via NGS of Usher Syndrome: type ID with heterozygous the nine gene Usher syndrome panel. variants in CDH23 and PCDH15 & type IIC Please refer to our “A Guide to Next- with heterozygous variants in the genes AD- Generation Sequencing” information 1. A negative result after NGS GRV1 and PDZD7. sheet available on our website, for further testing does not rule out the details. presence of a deletion or WHO SHOULD BE TESTED? duplication. Deletion/duplication INTERPRETATION OF TEST testing is available through our  Individuals clinically suspected of being RESULTS laboratory. If clinically indicated, affected with Usher syndrome. Genetic testing may reveal one or more please contact us to discuss this testing.  Relatives of a proband with identified variants in the Usher syndrome genes, pathogenic variant(s) in an Usher syndrome- which should be interpreted in the context 2. The clinical course or associated gene. of the suspected clinical diagnosis, severity of symptoms cannot be inheritance pattern, clinical findings, predicted by molecular analysis.  Pregnancies at increased risk due to a family history and other experimental data. 3. Test results should be family history of a Usher syndrome. Please refer to our “A Guide to Interpreting interpreted in the context of Sequence Variations” information sheet clinical findings, family history available on our website, for further details. and other laboratory data. 4. Current molecular testing Genes Types of Usher syndrome may not detect all possible mutations for this disease. A MYO7A Type IB negative test does not rule out USH1C Type IC the possibility of Usher syndrome. CDH23 Type ID 5. This test was developed PCDH15 Type ID and its performance USH1G Type IG characteristics validated by the Molecular Genetics Laboratory CIB2 Type IJ at the Hospital for Sick Children. It has not been USH2A Type IIA cleared or approved by the ADGRV1 Type IIC U.S. Food and Drug Administration. The FDA has PDZD7 Type IIC determined that such clearance WHRN Type IID or approval is not necessary. CLRN1 Type III Aug 2017 OMG1620BB/02