Diagnostic Criteria

Suggestive Findings

Mitochondrial nonsyndromic hearing loss and deafness should be suspected in a proband with the following:

• Moderate-to-profound hearing loss

Hearing loss graded by level of severity:

• Mild (26-40 dB)

• Moderate (41-55 dB)

• Moderately severe (56-70 dB)

• Severe (71-90 dB)

• Profound (90 dB)

Hearing is assessed by a variety of methods; see Hereditary Hearing Loss and Deafness Overview.

• Mild-to-moderate high-frequency hearing loss

• No other systemic findings on history or physical examination

• A family history of hearing loss suggestive of maternal inheritance (i.e., no transmission through a male)

• Onset of hearing loss following administration of an aminoglycoside antibiotic such as gentamycin, tobramycin, amikacin, kanamycin, or streptomycin

Establishing the Diagnosis

The diagnosis of mito...

Source: GeneReviews — "Nonsyndromic Hearing Loss and Deafness, Mitochondrial"

Differential Diagnosis

Other genetic causes of nonsyndromic hearing loss and deafness need to be considered (see Hereditary Hearing Loss and Deafness Overview and Mitochondrial Disorders Overview). Aminoglycoside drug toxicity. The hearing loss seen after use of aminoglycosides in individuals without the MT-RNR1 pathogenic variants or results from drug toxicity and is related to the dose administered and the metabolism of the drug (i.e., the peak and trough serum concentrations). Maternally inherited diabetes mellitus and deafness (MIDD; OMIM 520000). A single base-pair substitution of A to G at position 3243 (m.3243AG) in MT-TL1 (NC_012920.1), which encodes tRNA leucine, is associated with MIDD . MIDD accounts for 0.5%-2.8% of diabetes mellitus.

Source: GeneReviews — "Nonsyndromic Hearing Loss and Deafness, Mitochondrial"

Management Guidelines

Evaluations Following Initial Diagnosis

To establish the extent of hearing loss and needs in an individual diagnosed with mitochondrial nonsyndromic hearing loss and deafness, the following evaluations (if not performed as part of the evaluation that led to the diagnosis) are recommended:

• Complete auditory assessment (See Hereditary Hearing Loss and Deafness Overview.)

• Examination of the skin for evidence of keratoderma

• Consultation with a clinical geneticist and/or genetic counselor

Treatment of Manifestations

Treatment includes the following:

• Appropriate rehabilitation including hearing aids, speech therapy, culturally appropriate language training, and evaluation for eligibility for cochlear implantation

• Electric acoustic stimulation (EAS) for individuals with mitochondrial hearing loss with residual hearing in the lower frequencies

• Enrollment in educational programs appropriate for the hearing impaired

• For mild keratoderma, use of lotions and emollients; for severe keratoderma, dermatologic evaluation

Prevention of Primary Manifestations

MT-RNR1-related aminoglycoside-induced ototoxicity. Physicians can inquire about a family history of aminoglycoside-induced hearing loss prior to the administration of aminoglycosides, either systemically or locally (e.g., into the cochlea as treatment for Meniere's disease). In individuals with a family history of aminoglycoside-induced hearing loss, alternatives to aminoglycoside treatment should be considered when possible.

Source: GeneReviews — "Nonsyndromic Hearing Loss and Deafness, Mitochondrial"

Clinical Guidance

Aminoglycosides and noise exposure should be avoided, particularly in individuals with normal hearing who have the or MT-RNR1 pathogenic variant.

Source: GeneReviews — "Nonsyndromic Hearing Loss and Deafness, Mitochondrial"

Surveillance Guidelines

The following are appropriate:

• Annual audiometric assessment to evaluate stability or progression of hearing loss

• Annual examination by a physician to assess for related clinical findings (e.g., palmoplantar keratosis)

Source: GeneReviews — "Nonsyndromic Hearing Loss and Deafness, Mitochondrial"