Infantile spinal muscular atrophy with respiratory distress type I presenting without respiratory involvement: Novel mutations and review of the literature

Brain Dev. 2016 Aug;38(7):685-9. doi: 10.1016/j.braindev.2016.02.001. Epub 2016 Feb 24.


Spinal muscular atrophy with respiratory distress type 1 (SMARD1), also known as distal spinal muscular atrophy 1 (DSMA1) or distal hereditary motor neuropathies type 6 (dHMN6), is a rare autosomal recessive motor neuron disorder that affects infants and is characterized by diaphragmatic palsy, distal muscular weakness and muscle atrophy. The disease is caused by mutations in the gene encoding immunoglobulinm-binding protein 2 (IGHMBP2). We present a female child with novel compound heterozygous mutations in IGHMBP2 gene c.344C>T (p.115T>M) and c.1737C>A (p.579F>L), displaying distal limbs weakness and atrophy without signs of diaphragmatic palsy or respiratory insufficiency. We review 20 reported SMARD1 cases that have no respiratory involvement or have late onsets. We propose that IGHMBP2 gene mutations are characterized by significant phenotypic heterogeneity. Diaphragmatic palsy and respiratory distress may be absent and SMARD1 should be considered in infantile with the onset of peripheral neuropathies.

Keywords: Diaphragmatic palsy; IGHMBP2; Peripheral neuropathy; Respiratory involvement; Spinal muscular atrophy with respiratory distress type 1 (SMARD1).

Publication types

  • Case Reports
  • Review

MeSH terms

  • Age of Onset
  • Child, Preschool
  • DNA-Binding Proteins / genetics*
  • Female
  • Humans
  • Muscular Atrophy, Spinal / diagnosis
  • Muscular Atrophy, Spinal / genetics*
  • Muscular Atrophy, Spinal / pathology
  • Muscular Atrophy, Spinal / physiopathology*
  • Mutation
  • Respiratory Distress Syndrome, Newborn / diagnosis
  • Respiratory Distress Syndrome, Newborn / genetics*
  • Respiratory Distress Syndrome, Newborn / pathology
  • Respiratory Distress Syndrome, Newborn / physiopathology*
  • Respiratory Insufficiency / diagnosis
  • Respiratory Insufficiency / genetics
  • Respiratory Insufficiency / physiopathology
  • Transcription Factors / genetics*


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

Supplementary concepts

  • Spinal muscular atrophy with respiratory distress 1