The wide spectrum of clinical phenotypes of spinal muscular atrophy with respiratory distress type 1: a systematic review

J Neurol Sci. 2014 Nov 15;346(1-2):35-42. doi: 10.1016/j.jns.2014.09.010. Epub 2014 Sep 16.


Spinal muscular atrophy with respiratory distress type 1 (SMARD1), also known as distal spinal-muscular atrophy 1 (DSMA10), is an autosomal recessive type of spinal muscular atrophy that is related to mutations in the IGHMBP2 gene, which encodes for the immunoglobulin μ-binding protein. SMARD1 patients usually present low birth weight, diaphragmatic palsy and distal muscular atrophy. Clinical features are still the most important factor that leads to the diagnosis of SMARD1, due to the fact that IGHMBP2 gene mutations are characterized by significant phenotypic heterogeneity. In the present review, we will systematically discuss the genetic, clinical and neuropathological features of SMARD1 in order to provide a complete overview of SMARD1 variable clinical presentations and of the most important diagnostic tools which can be used to identify and properly manage affected individuals. This background is crucial also in the perspective of the development of novel therapeutic strategies for this still orphan disorder.

Keywords: Clinical presentations; Diagnostic criteria; IGHMBP2 gene; Immunoglobulin μ binding protein; Infantile neuromuscular disorders; SMARD1.

Publication types

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

MeSH terms

  • Autonomic Nervous System Diseases / etiology
  • DNA-Binding Proteins / genetics*
  • Humans
  • Muscular Atrophy, Spinal / complications
  • Muscular Atrophy, Spinal / diagnosis*
  • Muscular Atrophy, Spinal / genetics*
  • Mutation / genetics*
  • Neuroimaging
  • Respiratory Distress Syndrome, Newborn / complications
  • Respiratory Distress Syndrome, Newborn / diagnosis*
  • Respiratory Distress Syndrome, Newborn / genetics*
  • Transcription Factors / genetics*


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

Supplementary concepts

  • Spinal muscular atrophy with respiratory distress 1