Type 0 Spinal Muscular Atrophy: Further Delineation of Prenatal and Postnatal Features in 16 Patients

J Neuromuscul Dis. 2016 Nov 29;3(4):487-495. doi: 10.3233/JND-160177.


Background: Spinal muscular atrophy (SMA) is caused by homozygous inactivation of the SMN1 gene. The SMN2 copy number modulates the severity of SMA. The 0SMN1/1SMN2 genotype, the most severe genotype compatible with life, is expected to be associated with the most severe form of the disease, called type 0 SMA, defined by prenatal onset.

Objective: The aim of the study was to review clinical features and prenatal manifestations in this rare SMA subtype.

Methods: SMA patients with the 0SMN1/1SMN2 genotype were retrospectively collected using the UMD-SMN1 France database.

Results: Data from 16 patients were reviewed. These 16 patients displayed type 0 SMA. At birth, a vast majority had profound hypotonia, severe muscle weakness, severe respiratory distress, and cranial nerves involvement (inability to suck/swallow, facial muscles weakness). They showed characteristics of fetal akinesia deformation sequence and congenital heart defects. Recurrent episodes of bradycardia were observed. Death occurred within the first month. At prenatal stage, decreased fetal movements were frequently reported, mostly only by mothers, in late stages of pregnancy; increased nuchal translucency was reported in about half of the cases; congenital heart defects, abnormal amniotic fluid volume, or joint contractures were occasionally reported.

Conclusion: Despite a prenatal onset attested by severity at birth and signs of fetal akinesia deformation sequence, prenatal manifestations of type 0 SMA are not specific and not constant. As illustrated by the frequent association with congenital heart defects, type 0 SMA physiopathology is not restricted to motor neuron, highlighting that SMN function is critical for organogenesis.

Keywords: Spinal muscular atrophy; congenital heart defect; fetal akinesia deformation sequence; human SMN2 protein; prenatal ultrasonography.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arthrogryposis / etiology
  • Arthrogryposis / physiopathology*
  • Autonomic Nervous System Diseases / etiology
  • Autonomic Nervous System Diseases / physiopathology*
  • Cranial Nerve Diseases / etiology
  • Cranial Nerve Diseases / physiopathology*
  • Female
  • Genotype
  • Heart Defects, Congenital / diagnostic imaging
  • Heart Defects, Congenital / etiology
  • Heart Defects, Congenital / physiopathology*
  • Homozygote
  • Humans
  • Infant, Newborn
  • Life Expectancy
  • Male
  • Muscle Hypotonia / etiology
  • Muscle Hypotonia / physiopathology*
  • Reflex, Abnormal
  • Respiratory Distress Syndrome, Newborn / etiology
  • Respiratory Distress Syndrome, Newborn / physiopathology*
  • Spinal Muscular Atrophies of Childhood / complications
  • Spinal Muscular Atrophies of Childhood / diagnostic imaging
  • Spinal Muscular Atrophies of Childhood / genetics
  • Spinal Muscular Atrophies of Childhood / physiopathology*
  • Survival of Motor Neuron 1 Protein / genetics
  • Survival of Motor Neuron 2 Protein / genetics
  • Ultrasonography, Prenatal


  • SMN1 protein, human
  • SMN2 protein, human
  • Survival of Motor Neuron 1 Protein
  • Survival of Motor Neuron 2 Protein

Supplementary concepts

  • Pena Shokeir syndrome, type 1