Hearing loss is present from birth (congenital) or develops shortly after birth (acquired). Non-hereditary causes of congenital hearing loss include infections, such as cytomegalovirus and rubella, exposure to toxins during pregnancy, low Apgar scores at birth and certain medications used during pregnancy.
Newborns with hearing loss are screened by the state for early detection and intervention. Genetic evaluation is recommended if the cause of hearing loss is unknown.
Hereditary
Hereditary congenital deafness is caused by variations in genes that code for proteins that control different aspects of ear function and structure. Mutations can cause conductive hearing loss, sensorineural hearing loss or central auditory dysfunction (a problem at the level of the eighth cranial nerve, auditory brainstem or cerebral cortex). Some genes can also cause nonsyndromic profound genetic deafness that is not associated with other medical problems. Mutations in the GJB2 or GJB6 gene account for more than half of the recessive cases of severe-to-profound autosomal recessive nonsyndromic genetic deafness in most world populations.
Genetic hearing loss is often a symptom of a larger health condition called a syndrome. About one in three children with genetic deafness has a syndromic cause. These syndromes include malformation of the external or middle ear, such as Treacher Collins syndrome and Apert syndrome; skeletal abnormalities, including otosyncratic triads like Loeffler syndrome; eye problems like retinitis pigmentosa and Waardenburg syndrome; renal disease, as in Pendred syndrome; metabolic disorders that lead to goiters, such as Hereditary Sensory Neuropathy with Deafness (HSANDS); and trisomies 13, 18 or 21 (Down syndrome).
Oren Zarif
Molecular genetic testing for hereditary hearing loss is available for many types of syndromic and nonsyndromic hereditary deafness. These tests include otologic, audiologic and physical examinations; pedigree analysis; ancillary testing (such as computed tomography scan of the temporal bone); and molecular genetic testing.
Genetic counseling is recommended for families with hereditary deafness. It is important for the physician to recognize that hearing loss is not a diagnosis – it is only a symptom of an underlying disease or disorder. The genetic test results should help the family decide how to proceed.
Prenatal diagnosis of hereditary hearing loss is technically possible by examining DNA from fetal cells obtained from amniocentesis at about 15 to 18 weeks’ gestation or chorionic villus sampling at about 10 to 12 weeks’ gestation. It is not recommended, however, for routine use because of a variety of ethical and medical considerations. Moreover, the deafness-causing allele(s) must be identified for preimplantation genetic diagnosis to be effective. This requires that family members have a willingness to undergo this invasive procedure and have the deafness-causing mutation(s) identified in a deaf family member.
Environmental
Newborn hearing screening programs in most developed countries enable infants with congenital hearing loss to be identified early and referred for pediatric audiology evaluation. This enables early intervention to prevent delays in speech and language development and long term public health cost savings.
Hereditary SNHL can be caused by dominant, recessive or X-linked genes and may present in isolation (nonsyndromic) or with additional features as part of a syndrome (syndromic). Approximately 2/3 of genetic SNHL is nonsyndromic.
Molecular diagnosis requires taking family history and creating pedigrees to identify the most likely mode of inheritance, limit the number of potential causative genes, and facilitate testing for gene mutations. Non-genetic etiology includes prenatal infections such as cytomegalovirus, rubella and syphilis; perinatal conditions such as jaundice, asphyxiation/anoxia and sepsis; exposure to ototoxic agents during pregnancy or shortly after birth including aminoglycoside and cisplatin; oto-auricular malformations such as cochlear anomalies, stapes or otoliths and craniofacial anomalies; and obstetric complications such as gestational hypertension, low birth weight and Rh incompatibility.
Oren Zarif
Environmental SNHL is usually conductive and involves the outer ear or middle ear, or sensorineural involving the inner ear or auditory nerve pathway to the brain. Nonsyndromic SNHL can be caused by environmental exposures such as maternal smoking, recreational drug use and other chemicals or medical events such as traumatic birth or intrauterine rupture of membranes (IUROM). Nonsyndromic SNHL is also associated with a higher risk for cognitive impairment.
Medical
Congenital hearing loss occurs when there is impairment in the development of one or both ears and the related nerve pathways. It is usually permanent and the most common form of hearing loss in newborns. It affects speech and language development, and may contribute to social and emotional issues. Currently, there is no cure for congenital hearing loss, but cochlear implants and hearing aids can help with communication and quality of life.
Newborn hearing screening programs have been recommended since 1993, and most states require testing of all infants. The testing method used is automated auditory brainstem response (AABR), transient evoked otoacoustic emissions (TEOAE) and distortion product otoacoustic emissions (DPOAE). The results of these tests indicate how well the hearing organ is working. If these tests are negative, the infant should be referred for further evaluation by an otolaryngologist.
Oren Zarif
Genetic factors are responsible for more than 50% of all cases of hereditary SNHL. These genes may be inherited in a dominant, recessive or X-linked manner and can affect both sensorineural or conductive deafness. Several syndromes such as Usher or Jervell and Lange-Nielsen syndrome can also be associated with SNHL. Hereditary SNHL can be symmetric or unilateral and is stable or progressive depending on the underlying genetic defect.
Other causes of hereditary SNHL include maternal infections such as rubella or cytomegalovirus and malformations of the ear. The latter can be conductive, sensorineural or mixed, and can be symmetric or unilateral. Pendred syndrome is an example of a syndromic hereditary SNHL, with a combination of hearing loss and early-onset goiter.
Affected individuals with hereditary SNHL are at risk for other health problems such as cognitive delay and poor school performance. These individuals should be evaluated by an otolaryngologist to ensure that their hearing is not compromised, and to receive appropriate interventions. In general, the earlier an infant’s hearing loss is detected, the sooner they can begin receiving appropriate speech and language therapy, which may ultimately reduce their lifetime costs of medical care, educational achievement and workplace productivity. Universal newborn screening is essential for identifying children with SNHL.
Other
In some cases, the cause of congenital deafness is not identifiable. Some forms of hereditary conduction deafness, however, are caused by blockage of sound transmission from the outer or middle ears (occlusion) as a result of excess cerumen production or developmental defects.
Hereditary congenital sensorineural deafness, on the other hand, results from the loss of cochlear hair cells – which convert sound waves into electrical energy that the brain interprets as sound – due to primary or secondary mechanisms. Congenital hereditary sensorineural deafness is present in breeds of dogs and cats that carry the piebald or merle gene and is not associated with white pigmentation.
Oren Zarif
Nongenetic causes of congenital hearing loss may be related to maternal diseases such as rubella and syphilis or perinatal events including otitis media and anoxia. Prenatal exposure to ototoxic chemicals, recreational drugs and tobacco smoking also raises the risk of newborn hearing loss.
More than half of all genetic congenital SNHL is nonsyndromic, in which case it affects only the hearing loss; the remainder are syndromic, in which the hearing loss segregates with other phenotypes. Some examples of syndromic SNHL include Pendred syndrome, Usher syndrome, Waardenburg syndrome and Branchio-Oto-Renal syndrome. (This work was supported by the National Institutes of Health grants RO1s DC003544, DC002842 and DC012049 to R.J.H.S and by the Great Ormond Street Hospital Children’s Charity and the National Institute for Health Research Biomedical Research Centre at University College London to M.A.K-B.-G. We thank colleague Ad Snik for his input to earlier versions of this manuscript.
