Sensorineural hearing impairment in patients with Pmp22 duplication, deletion, and frameshift mutations

Otol Neurotol. 2005 May;26(3):405-14. doi: 10.1097/01.mao.0000169769.93173.df.

Abstract

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.

MeSH terms

  • Adult
  • Aged
  • Aging
  • Audiometry, Pure-Tone
  • Audiometry, Speech
  • Auditory Threshold
  • Charcot-Marie-Tooth Disease / genetics
  • Cross-Sectional Studies
  • Disease Progression
  • Frameshift Mutation*
  • Gene Deletion*
  • Gene Duplication*
  • Hearing
  • Hearing Loss, Sensorineural / diagnosis
  • Hearing Loss, Sensorineural / genetics*
  • Hearing Loss, Sensorineural / physiopathology
  • Humans
  • Linear Models
  • Middle Aged
  • Myelin Proteins / genetics*
  • Presbycusis / physiopathology
  • Prospective Studies

Substances

  • Myelin Proteins
  • PMP22 protein, human