Genetics of Hearing Loss

Abstract

Synopsis Hearing loss (HL) is one of the most common birth defects in developed countries and is a diverse pathology with different classifications. One of these is based on the association with other clinical features, defined as syndromic hearing loss (SHL). Determining the etiology of the HL in these patients is extremely beneficial as it enables a personalized approach to caring for the individual. Early screening can further aid in optimal rehabilitation for a child’s development and growth. Pathogenic variants in forty-five genes, encoding proteins functioning as ion channels, transcription factors, molecular motors and more, are known to lead to eleven forms of SHL. The development of high-throughput sequencing technology is facilitating rapid and low-cost diagnostics for patients with SHL.

Acquired Hearing Loss in Children

“…4,5 Genetic causes of hearing loss, however, may present later in childhood, seemingly as an acquired hearing loss, so genetic causes should always be considered, especially if other causes are not readily identified. For example, hearing loss associated with GJB2 (connexin 26) may present as very mild, or even normal, in the newborn period, then go on to progressively worsen.…”

Diagnosis and Treatment of Congenital Sensorineural Hearing Loss

“…For example, patients with Jervell and Lange-Nielsen syndrome have an increased incidence of syncope and sudden death due to a mutation in the potassium channel gene that leads to conduction abnormalities in the heart in addition to profound sensorineural hearing loss. 8 …”

Moderate-Severe Hearing Loss in Children: A Diagnostic and Rehabilitative Challenge

“…Syndromic hearing loss is associated with dimorphisms and/or signs/ symptoms/malformations of other organs [53,54] . More than 400 syndromes linked to hearing loss have been described so far, but the diagnosis may be difficult as: (i) the genetics of these syndromes is heterogeneous and with a variable penetrance and (ii) different mutations of the same gene may be linked to both non-syndromic and syndromic hearing loss [55] . Waardenburg syndrome (characterized by mono-or bilateral mild-to-severe SNHL, associated with typical hair, skin, and eyes dyschromic manifestations) and branchio-oto-renal (BOR) syndrome (involving branchial arch anomalies; inner, middle, and external ear malformations; hearing loss; and kidney defects [56] ) are among the most frequent causes of autosomal dominant syndromic hearing loss.…”

“…Pendred syndrome is the most common autosomal recessive syndrome of hearing impairment [55] . It is due to PDS gene mutation, encoding for a protein called pendrin (also known as SLC26A4, solute carrier family 26, member 4), involved in calcium and iodine transport; it has a recessive autosomal transmission modality.…”

“…Pendred syndrome is characterized by congenital or generally preverbal bilateral profound SNHL, associated with non-endemic goiter, temporal bone anomalies, enlarged vestibular aqueduct, and, sometimes, mental retardation and cerebellar signs. Usher syndrome, with autosomal recessive inheritance, represents the most common form of hearing impairment and vision loss during infancy [55] .…”