Spinal muscular atrophy with respiratory distress type 1: Clinical phenotypes, molecular pathogenesis and therapeutic insights

J Cell Mol Med. 2020 Jan;24(2):1169-1178. doi: 10.1111/jcmm.14874. Epub 2019 Dec 4.


Spinal muscular atrophy with respiratory distress type 1 (SMARD1) is a rare autosomal recessive neuromuscular disorder caused by mutations in the IGHMBP2 gene, which encodes immunoglobulin μ-binding protein 2, leading to progressive spinal motor neuron degeneration. We review the data available in the literature about SMARD1. The vast majority of patients show an onset of typical symptoms in the first year of life. The main clinical features are distal muscular atrophy and diaphragmatic palsy, for which permanent supportive ventilation is required. No effective treatment is available yet, but novel therapeutic approaches, such as gene therapy, have shown encouraging results in preclinical settings and thus represent possible methods for treating SMARD1. Significant advancements in the understanding of both the SMARD1 clinical spectrum and its molecular mechanisms have allowed the rapid translation of preclinical therapeutic strategies to human patients to improve the poor prognosis of this devastating disease.

Keywords: IGHMBP2; Spinal muscular atrophy with respiratory distress type 1; gene therapy; motor neuron disease.

Publication types

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

MeSH terms

  • Animals
  • DNA-Binding Proteins / genetics*
  • Humans
  • Molecular Targeted Therapy*
  • Muscular Atrophy, Spinal / genetics
  • Muscular Atrophy, Spinal / pathology*
  • Muscular Atrophy, Spinal / therapy*
  • Mutation*
  • Prognosis
  • Respiratory Distress Syndrome, Newborn / genetics
  • Respiratory Distress Syndrome, Newborn / pathology*
  • Respiratory Distress Syndrome, Newborn / therapy*
  • Transcription Factors / genetics*


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

Supplementary concepts

  • Spinal muscular atrophy with respiratory distress 1