PMP22 related neuropathies: Charcot-Marie-Tooth disease type 1A and Hereditary Neuropathy with liability to Pressure Palsies

Orphanet J Rare Dis. 2014 Mar 19;9:38. doi: 10.1186/1750-1172-9-38.

Abstract

PMP22 related neuropathies comprise (1) PMP22 duplications leading to Charcot-Marie-Tooth disease type 1A (CMT1A), (2) PMP22 deletions, leading to Hereditary Neuropathy with liability to Pressure Palsies (HNPP), and (3) PMP22 point mutations, causing both phenotypes. Overall prevalence of CMT is usually reported as 1:2,500, epidemiological studies show that 20-64% of CMT patients carry the PMP22 duplication. The prevalence of HNPP is not well known. CMT1A usually presents in the first two decades with difficulty walking or running. Distal symmetrical muscle weakness and wasting and sensory loss is present, legs more frequently and more severely affected than arms. HNPP typically leads to episodic, painless, recurrent, focal motor and sensory peripheral neuropathy, preceded by minor compression on the affected nerve. Electrophysiological evaluation is needed to determine whether the polyneuropathy is demyelinating. Sonography of the nerves can be useful. Diagnosis is confirmed by finding respectively a PMP22 duplication, deletion or point mutation. Differential diagnosis includes other inherited neuropathies, and acquired polyneuropathies. The mode of inheritance is autosomal dominant and de novo mutations occur. Offspring of patients have a chance of 50% to inherit the mutation from their affected parent. Prenatal testing is possible; requests for prenatal testing are not common. Treatment is currently symptomatic and may include management by a rehabilitation physician, physiotherapist, occupational therapist and orthopaedic surgeon. Adult CMT1A patients show slow clinical progression of disease, which seems to reflect a process of normal ageing. Life expectancy is normal.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Arthrogryposis / diagnosis
  • Arthrogryposis / genetics*
  • Arthrogryposis / therapy
  • Charcot-Marie-Tooth Disease / genetics*
  • Charcot-Marie-Tooth Disease / therapy
  • Genetic Counseling
  • Genetic Predisposition to Disease*
  • Hereditary Sensory and Motor Neuropathy / diagnosis
  • Hereditary Sensory and Motor Neuropathy / genetics*
  • Hereditary Sensory and Motor Neuropathy / therapy
  • Humans
  • Myelin Proteins / genetics*
  • Point Mutation
  • Prognosis

Substances

  • Myelin Proteins
  • PMP22 protein, human

Supplementary concepts

  • Tomaculous neuropathy