Genes and syndromic hearing loss.

UNLABELLED: Syndromes that are associated with hearing loss include Waardenburg, Stickler (STL), Jervell and Lange-Nielsen, Usher (USH), Alport, mitochondrial encephalomyopathy, lactic acidosis, stroke-like episodes, and sensorineural hearing loss (MELAS) and mitochondrial encephalomyopathy, myoclonus epilepsy, ragged-red fibers, and sensorineural hearing loss (MERRF). Waardenburg and STL show an autosomal dominant pattern of inheritance, while Jervell and Lange-Nielsen and USH are autosomal recessive, and Alport is usually X-linked. Mutations in specific genes that are associated with each of these syndromes have been identified, and genetic diagnostic tests are becoming available. The goal of ongoing research is to understand the functions of the proteins encoded by these genes, and develop effective therapies based on knowledge of the underlying causal mutations.

LEARNING OUTCOMES: The reader will be introduced to basic genetic principles and will understand that (1) the etiology of hearing loss is usually genetic and many patients should be referred to a clinical geneticist; (2) a negative family history does not mean that the hearing loss is not genetic; (3) hearing loss may be part of a syndrome for which early detection and intervention for associated anomalies is necessary; and (4) many different mutations in a large number of genes underlie hearing loss.