Genetic Sensorineural Hearing Loss Workup

Routine series of laboratory tests are not recommended in the evaluation of a hearing impaired patient. Rational assessment of the cost-benefit ratio and the clinician's index of suspicion should guide the selection of laboratory studies for an individual patient. Studies may include those listed below.

• Molecular genetic testing. ^[2] Assays are available for the following:

  • GJB2 (connexin 26)

  • Mitochondrial gene mutations in the 12SrRNA and tRNAser(UCN) genes (aminoglycoside-sensitive SNHL)

  • OTOF (associated with auditory neuropathy in some patients and nonsyndromic hearing loss in other patients)

  • GJB6 gene (connexin 30)

  • SLC26A4 (Pendred syndrome)

  • CDH23 (cadherin) and MYO7A (myosin), which account for approximately 70% of the mutations that cause Usher syndrome type I

  • COCH (associated with adult-onset dominant SNHL).

  • Genetic testing is available for a number of other genes, but the infrequency of most of them makes routine clinical testing impractical.

• Complete blood count (CBC) with differential

• Chemistries

• Blood sugar determination

• BUN and creatinine measurement

• Thyroid studies

• Urinalysis

• Fluorescent treponemal antibody absorption (FTA-ABS) test

• Specific immunoglobulin M (IgM) assays for toxoplasmosis, rubella, CMV infection

• Herpes virus autoimmune panel

• Autoimmune profile

  • Test of erythrocyte sedimentation rate (ESR)

  • Antinuclear antibody (ANA) test

  • Rheumatoid factor (RF) test

  • Measurement of complement levels

  • Raja-cell studies

  • Western blot (to identify serum anti-68 kd autoantibody)

  • Tests for circulating immune complexes

See the list below:

• CT scanning offers high-resolution images with 1-mm sections, which permit good visualization of the anatomy of the bones, ossicles, and inner ear.

  • CT assists in the diagnosis of suspected labyrinthine anomalies, such as a large vestibular aqueduct or Mondini dysplasia. CT scanning is also useful for diagnosing suspected labyrinthine fistula or temporal bone fractures.

  • CT may help in identifying the relatively nondysplastic and presumably somewhat-hearing ear when auditory habilitation is being considered.

  • A common abnormality noted on CT is an enlarged vestibular aqueduct. It is typically defined as an anteroposterior diameter of more than 1.5 mm at the operculum, but some clinicians and authors use a definition broader than this. Hearing loss associated with enlarged vestibular aqueduct is usually bilateral and progressive, and it may be associated with vertigo. It has an associate with Pendred and Mondini malformations.

• MRI has high soft tissue contrast, which makes it ideal for evaluation of the inner ear, internal auditory canal, and cerebellopontine angle.

  • MRI with gadolinium enhancement is the criterion standard for evaluating potential retrocochlear pathology as a cause of hearing loss.

  • Highly T2-weighted images obtained with appropriate sagittal sections can depict aplasia of the cochlear nerve and subtle malformations of the inner ear.

See the list below:

• Auditory brainstem response (ABR): ABR is most clinically useful for assessment of infants and young children.

  • Principle areas of application include the evaluation and diagnosis of the peripheral auditory system and related pathology and determination of the neural integrity of the acoustic nerve and brainstem pathway.

  • ABR provides a valid estimate of auditory sensitivity based on the threshold of response.

• Audiometry: Valid and reliable techniques are presently available to provide information relevant to presence, degree, and nature of hearing impairment in children within the first 24 hours of life.

  • Visual response audiometry yields precise information regarding auditory sensitivity in infants as young as 6 months. Head-turning responses to sound are conditioned through visual reinforcement, and ultimately the response behavior is controlled.

  • Play audiometry is ideal for children aged 2-5 years and for older children who are mentally or developmentally delayed. Conventional audiometric techniques are combined with testing situations in which the child can respond appropriately to stimuli by participating in a form of play activity. Hearing levels can be assessed for both speech and pure tone stimuli.

  • Conventional audiometry is traditionally reserved for children aged 3-5 years and older. Techniques include pure tone and speech audiometry (to determine air and bone conduction thresholds) and speech recognition.

  • Immittance audiometry provides an objective, rapid, and accurate assessment of middle ear function in infants and children. Immittance audiometry consists of 2 primary techniques, tympanometry and measurement of acoustic-reflex thresholds.

    • Tympanometry reflects the compliance of the middle ear system as the eardrum is artificially altered with varying degrees of air pressure in the external auditory canal (EAC). A noncompliant middle ear is consistent with effusion, which is a typical presentation in the infant population.

    • The acoustic-reflex threshold measurement is defined as the lowest intensity level that elicits stapedial muscle contraction. The acoustic-reflex response typically is in the range of 85 dB for the midfrequency stimulus. Deviations in the acoustic-reflex response, including elevated or absent thresholds, are synonymous with middle ear dysfunction

• Otoacoustic emissions (OAEs): OAEs are samples of measurable acoustic energy generated by vibratory patterns in the normal cochlea and propagated into the EAC by way of the middle ear apparatus. Emissions provide an objective measure of auditory sensitivity, frequency analysis, and cochlear integrity.

  • The 2 primary categories of otoacoustic emissions are spontaneous OAEs (SOAEs) and evoked OAEs (EOAEs). EOAEs can be subdivided into transient and distortion product OAEs (DPOAEs) according to the stimulus characteristics used to elicit their response. Clinical application is limited in that SOAEs are recorded in only approximately half of the population.

  • Transient OAEs and DPOAEs can be recorded in nonpathologic ears that do not have hearing loss >20-30 dB regardless of sex or age. The absence of measurable EOAEs is strongly predictive of a decrease in peripheral hearing, particularly in the 2000- to 4000-Hz range, where EOAEs appear to be most sensitive to dysfunction of the outer hair cells.

• ECG: Consider ECG to detect cardiac conduction anomalies, especially in any child who has a family history of SIDS, syncope, cardiac dysrhythmia, or sudden death in a child.

Histologic examination of temporal bones of patients with genetic patterned hearing loss has shown a variety of patterns.

Macrostructural malformations include the following:

Michel dysplasia is characterized by complete failure of inner ear development, while the external and middle ears may be normal and functional. Complete unilateral or bilateral deafness may ensue. The diagnosis rests on postmortem histopathology because radiographic studies cannot differentiate between Michel dysplasia and labyrinthitis ossificans.

Mondini dysplasia is possibly due to arrested development of the cochlea in its embryonic stage at approximately the sixth week of gestation. Only the basal turn of the cochlea is developed, and the bony cochlea is restricted to 1.5 turns. Mondini dysplasia may manifest in early childhood or in adulthood, with hearing that ranges from complete loss to normal hearing. It is inherited in an autosomal dominant fashion.

Scheibe dysplasia is the most common form of congenital dysplasia of the inner ear and is also known as cochleosaccular dysplasia. The bony labyrinth, membranous utricle, and semicircular canals are fully formed, while pars inferior structures, namely the saccule and cochlear duct, are poorly differentiated. Scheibe dysplasia is often noted in congenital hearing losses with autosomal recessive inheritance.

Alexander aplasia is characterized by aplasia of the cochlear duct. The organ of Corti, particularly the basal turn of the cochlea and adjacent ganglion cells, is affected most prominently. Hearing loss is most notable with high frequencies, whereas low-frequency hearing is relatively preserved.

On a microstructural basis, the study of the histopathology of temporal bones from patients with genetic hearing loss has demonstrated a wide variety of abnormalities including: partial or complete hair cell loss, reduced number of or atrophy of nerve cells and fibers, loss of supporting cells, degeneration of the tectorial membrane, atrophic, absent or degenerated stria vascularis, or even complete loss of the organ of corti and other cochlear structures. ^[32]