Hearing loss is the most common sensory deficit in humans. Roughly one child in a thousand is born with hearing impairment significant enough to compromise the development of normal language skills. Hearing loss can be caused by environmental as well as genetic factors. Environmental causes include pre- and postnatal infection and ototoxic drug exposure. It is estimated, however, that 50-75% of all childhood deafness is due to hereditary causes. There are two main forms of genetic hearing loss, syndromic and nonsyndromic. Children with syndromic hearing loss have other clinical features in addition to the hearing loss. About 15-30% of the hereditary hearing loss is syndromic, while the vast majority is nonsyndromic (70%).
Over four hundred syndromes with hearing loss have been described.
The Online Mendelian Inheritance in Man (www.ncbi.nlm.nih.gov/Omim) has comprehensive descriptions of the clinical features and molecular genetics of these syndromes as well as an all-inclusive list of references.
For convenience, syndromes with hearing loss can be categorized by the association with other morphologic abnormalities. Important syndromes where deafness is associated with craniofacial abnormalities include Treacher-Collins, Goldenhar’s, Crouzon’s, and Apert’s syndromes. All except Goldenhar’s (autosomal recessive) are inherited in an autosomal dominant fashion. Hearing loss in these syndromes is mixed or conductive and may be surgically correctable.
Hearing loss in association with visual loss is a particularly devastating combination. There are four important syndromes with this combination: Usher’s, Alström’s, Cockayne’s and Refsum’s disease. All are inherited in an autosomal recessive fashion.
Apert’s syndrome consists of progressive renal insufficiency, progressive sensorineural hearing loss and various ocular abnormalities. This syndrome demonstrates X-linked dominant inheritance; males are more severely affected and females may have a variable course to their disease because of random X chromosome inactivation.
Jervell and Lange-Nielsen syndrome is the most common syndrome with cardiac dysfunction and hearing loss.
There is a conduction defect resulting in a prolonged QT interval on electrocardiogram. Clinically patients may present with fainting spells or sudden death. Jervell and Lange-Nielsen is inherited in an autosomal recessive manner.
Pendred’s syndrome is the most frequently occurring example of associated deafness and endocrine dysfunction. This disorder results from an error in thyroxin metabolism. A goiter may be clinically palpable and profound sensorineural hearing loss is usually present.
Skin abnormalities and deafness characterize Waardenburg syndrome and the LEOPARD syndrome. Metabolic syndromes, especially the mucopolysaccharidoses, are frequently associated with conductive or mixed hearing loss. Chromosomal abnormalities, specifically trisomy 13 and 18 are often associated with deafness. Because these conditions are lethal in early infancy, the deafness is of relatively minor significance. Down’s syndrome is often associated with a mixed hearing loss.
According to the Hereditary Hearing Loss homepage (www.uia.ac.be/dnalab/hhh/), 80 loci for nonsyndromic hearing loss have been mapped to the human genome, and 30 genes have been identified. Based on the type of gene product, these genes can be categorized into several groups.
There are autosomal dominant, autosomal recessive and X-linked forms of nonsyndromic hearing loss. In general, recessive inheritance shows prelingual onset of hearing loss. The severity is severe to profound with all frequencies affected. In autosomal dominant forms, the phenotype is less severe. The onset is usually postlingual. The severity ranges from moderate to severe. Hearing loss is seen in middle, high, or all frequencies with only three loci having hearing loss in the low-frequency range.
A complete history should include prenatal, perinatal, postnatal, and family history. It is important to inquire about hearing loss in first- and second-degree relatives, especially if the loss started before age 30. Consanguinity or common origin from ethnically isolated areas should increase suspicion of hereditary hearing loss. If there are a number of family members with hearing loss, constructing a pedigree is important.
Physical exam should focus on looking for features associated with congenital infection or syndromic hearing loss. Note hair color, the presence of a white forelock, facial shape, and skull shape. On eye examination, one should note the color of the iris, position of the medial and lateral canthus, intercanthal distance, cataracts, and any retinal findings. Examine the ear for preauricular pits, skin tags, shape and size of the pinna, or any abnormality of the external auditory canal or tympanic membrane. Examine the neck for branchial anomalies and thyroid enlargement, and the oral cavity for clefts. Thorough inspection of skin for areas of hyper- or hypopigmentation and café-au-lait spots. Do a complete neurological exam including gait and balance to evaluate vestibular function.
In addition to audiological testing, certain lab tests should be ordered based on the history and physical exam. For example, thyroid function tests and EKG in suspected Pendred syndrome and Jervell and Lange-Neilsen syndrome, respectively.
A CT scan of the temporal bone is the radiological test of choice for evaluation of pediatric sensorineural hearing loss and should be considered in all patients with progressive hearing loss and craniofacial anomalies. The most common finding is enlarged vestibular aqueduct, followed by Mondini malformation. Enlarged vestibular aqueduct (EVA) suggests the diagnosis of Pendred syndrome, but may be found in branchiootorenal syndrome or in isolation. All patients with documented EVA should be investigated for Pendred syndrome.
Genetic counseling is an important part of evaluation. The risks and benefits of genetic testing should be explained to the family and consent should be obtained before genetic testing. The most common genetic test available to date for nonsyndromic hearing loss is connexin. Knowing the genetic cause of a person’s hearing loss can lead to improved decision about treatment and management. Genetic information can help predict whether the hearing loss will remain the same or whether it will worsen over time. Knowledge of the genetic cause is also helpful in determining what kind of damage has happened to the hearing system to cause the deafness. This is important because how the inner ear is damaged may affect whether a cochlear implant, or other hearing device, may help a patient.
In addition, genetic testing can help determine if problems besides hearing loss may be present or may develop in the future. Genetic testing can also provide a deaf individual or the parents of a deaf child information when making reproductive choices.
The diagnosis and treatment of hearing loss is critical for normal speech and language. Hearing impairment during childhood can affect social and emotional development, behavior, attention, and academic achievement. It has been shown in multiple studies that children with hearing loss do not learn as well and eventually suffer in psychosocial growth and even in their socioeconomic performance.
To avoid these consequences, we must identify the hearing loss early and either amplify it or surgically correct it. Delay in diagnosis can be severe because schools are auditory verbal environments. Even mild or unilateral hearing loss may have a detrimental effect on the development of a young child. Some cases of hearing loss are misdiagnosed because affected children have sufficient hearing to respond to environmental sounds and they can even learn some speech and language, but when challenged in the classroom they cannot perform to full potential. Hearing loss should be considered in any child with speech and language difficulties or poor grades, poor behavior, or inattention in school.