CMT 1A & HNPP Sensorineural Hearing Impairment in Patients with Pmp22 Duplicatio

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Otol Neurotol. 2005 May;26(3):405-414.

Sensorineural Hearing Impairment in Patients with Pmp22 Duplication,

Deletion, and Frameshift Mutations.

Verhagen WI, Huygen PL, Gabreels-Festen AA, Engelhart M, van Mierlo

PJ, van Engelen BG.

*Department of Neurology, Canisius-Wilhelmina Hospital, and

daggerDepartment of Otolaryngology and double daggerNeuromuscular

Center Nijmegen, Institute of Neurology, University Medical Center,

Nijmegen, The Netherlands.

OBJECTIVE: To characterize and distinguish the types of sensorineural

hearing impairment (SNHI) that occur in hereditary motor and sensory

neuropathy Type 1a (HMSN-1a) and hereditary neuropathy with liability

to pressure palsies (HNPP), which are caused by deletion or

frameshift mutation.

STUDY DESIGN: Prospective study.

SETTING: Ambulatory patients in a university hospital.

PATIENTS: Twelve patients with HMSN-1a due to a duplication of the

PMP22 gene on chromosome 17p11.2, 16 patients with HNPP due to the

common PMP22 deletion (HNPP del), and 11 HNPP patients with a frame

shift mutation (heterozygous PMP22 G-insertion) (HNPP mut), all

confirmed by molecular genetic analysis.

INTERVENTIONS:: Pure-tone audiograms and speech audiograms were

obtained.

MAIN OUTCOME

MEASURES: Results of cross-sectional analysis comprising linear

regression of hearing threshold on age.

RESULTS: Pure-tone audiograms showed mild to moderate SNHI,

predominant at the low and the high frequencies. SNHI showed

significant progression by approximately 0.4 dB per year at 0.25 to 4

kHz and up to 1 to 2 dB per year at 4 to 8 kHz. Patients with HMSN-1a

had substantial, presumably congenital, SNHI but did not show

significant progression beyond presbyacusis. Patients with HNPP

showed postnatal onset at age 11 years with progression of SNHI in

excess of presbyacusis by 0.4 dB per year. All three types of

neuropathy showed normal speech recognition.

CONCLUSIONS:All three types of neuropathy showed SNHI with normal

speech recognition. HMSN-1a showed stable SNHI without progression

beyond presbyacusis. HNPP showed progression beyond presbyacusis with

postnatal onset. The differences in SNHI may be explained by the

differences in PMP22 expression. The progressive SNHI in HNPP might

be explained by the liability for exogenous factors associated with

this disorder.