Charcot Marie Tooth disease type 2S with late onset diaphragmatic weakness: An atypical case

Neuromuscul Disord. 2018 Dec;28(12):1016-1021. doi: 10.1016/j.nmd.2018.09.008. Epub 2018 Oct 5.

Abstract

Immunoglobulin-helicase-μ-binding protein 2 (IGHMBP2) mutations are associated with partial continuum between two extremes of rapidly lethal disorder of spinal muscular atrophy with respiratory distress type 1 (SMARD1), with infantile axonal neuropathy, diaphragmatic weakness and commonly death before 1 year of age, and Charcot-Marie-Tooth disease (CMT) type 2S with slowly progressive weakness and sensory loss but no significant respiratory compromise. We present an atypical case of CMT2S. A 9 month old boy presented with bilateral feet deformities and axonal neuropathy. Genetic testing revealed two heterozygous variants in the IGHMBP2 gene: c.1156 T > C p.(Trp386Arg) in exon 8 and c.2747G > A p.(Cys916Tyr) in exon 14, that were inherited from his father and mother respectively. At 9 years, he developed diaphragmatic weakness, following which he was established on non-invasive ventilation. Our case emphasizes the importance of life long respiratory surveillance for patients with CMT2S and expands the phenotype of this condition.

Keywords: CMT2S; Diaphragmatic weakness; IGHMBP2.

Publication types

  • Case Reports

MeSH terms

  • Charcot-Marie-Tooth Disease / diagnosis*
  • Charcot-Marie-Tooth Disease / genetics
  • Charcot-Marie-Tooth Disease / physiopathology
  • Child
  • Child, Preschool
  • DNA-Binding Proteins / genetics*
  • Diaphragm / physiopathology*
  • Humans
  • Infant
  • Male
  • Mutation
  • Respiration Disorders / diagnosis*
  • Respiration Disorders / genetics
  • Respiration Disorders / physiopathology
  • Transcription Factors / genetics*

Substances

  • DNA-Binding Proteins
  • IGHMBP2 protein, human
  • Transcription Factors