Proximal spinal muscular atrophy


A rare group of muscle disorders which mainly affects the muscles closest to the trunk of the body. Muscles become progressively weak and wasted due to damage to motor neurons in the spinal cord and brainstem.


  • Progressive muscle wasting
  • Reduced reflexes
  • Reduced muscle tone
  • Movement disorder
  • Abnormal rib number
  • Retarded fetal growth
  • Reduced amniotic fluid
  • Restricted joint mobility
  • Stillbirth
  • Infant death
  • Leg weakness
  • Fractures
  • Lymphoedema


Around 95% of cases of SMA are caused by homozygous deletions (either of exon 7, or of exons 7 and 8) in the SMN1 gene (5q12.2-q13.3) encoding the SMN (survival motor neuron) protein. A second SMN gene (SMN2; 5q13.2) has also been identified and contributes to the production of only 10% of the full-length SMN protein. However, although there is some variation, disease severity in SMA is inversely correlated with the number of copies of the SMN2 gene, with patients with three or four copies more frequently manifesting SMA3/4, rather than SMA1. Deletions of the NAIP (5q13.1) gene have also been identified and may play a role in modifying disease severity.


Diagnosis is based on clinical history and examination and can be confirmed by genetic testing. Muscle biopsy and Electromyography  may also be performed.


Depends on the severity of the disease, which generally correlates with the age of onset: earlier-onset forms are generally associated with a poor prognosis, whereas life expectancy may be close to normal in later-onset forms. Death may occur due to respiratory insufficiency and infections.


Remains symptomatic, involving a multidisciplinary approach that aims to improve quality of life. Physiotherapy, occupational and respiratory therapies are necessary. Noninvasive ventilation and gastrostomy may be required. Antibiotic therapy is used in case of pulmonary infection. The scoliosis and joint manifestations may require surgical correction. Patients may require a wheelchair, or use a corset/back brace for support.

Clinical trials are ongoing to identify potential drug treatments for SMA, mainly targeted towards increasing the levels of the full length SMN protein.