Kugelberg Welander Spinal Muscular Atrophy Clinical Presentation

Updated: Sep 01, 2021
  • Author: Joyce L Oleszek, MD; Chief Editor: Stephen Kishner, MD, MHA  more...
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  • Patients with spinal muscular atrophy types III and IV usually present with an insidious onset of weakness, often following a brief period of illness, such as with influenza. The illness may have required a short period of bed rest.

  • Patients most often report symptoms associated with weakness of the hip extensor and hip abductor muscles and describe difficulty climbing stairs or getting up from a seated position on the floor.

  • Some patients also may report a mild tremor and occasional, painful muscle cramps.

  • Difficulty walking or running also is reported by the patient.

  • Parents of younger patients may report delayed developmental milestones or decreased athletic abilities in their children.

  • A family history of such disorders also may be elicited.



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  • Proximal muscle weakness is seen in spinal muscular atrophy, with the pelvic girdle being more affected than the shoulder girdle. [5]

  • Patients have decreased muscle tone.

  • Patients have diminished deep tendon reflexes. Ankle reflexes, however, may be preserved until very late in the disease's progress.

  • Fasciculations may be present in the tongue or shoulder girdle muscles (especially after manual muscle testing).

  • Minipolymyoclonus, a fine, irregular tremor of the outstretched fingers, may be seen. This is the result of denervation followed by reinnervation and the asynchronous firing of restructured and enlarged motor units.

  • Calf pseudohypertrophy has occasionally been noted, but muscle wasting of affected musculature is more prominent.

  • Patients may have a positive Gowers sign and a waddling gait.

  • Approximately one third of patients have facial and masseter muscle weakness.

  • Sensory examination findings are normal.



The exact etiology of spinal muscular atrophy (SMA) is unknown. SMA is an inherited disorder that almost always occurs in an autosomal recessive pattern. A few cases of autosomal dominant and X-linked recessive patterns have been reported.

All forms of SMA have been linked to a gene deletion on the long arm of chromosome 5, at band 5q13. The 2 genes associated with SMA are SMN1 (survival motor neuron 1) and SMN2, which are adjacent to each other on band 5q. SMN1 is believed to be the primary disease-causing gene. [16] SMN2 differs from it by 1 C-T transition in exon 7, leading to alternate splicing and a nonfunctional protein for 70-90% of the protein produced. [17] An attenuated disease severity and a milder phenotype appears to be correlated with the presence of 3 or more copies of SMN2.

Several mechanisms have been proposed for the relationship between the SMN genes and the natural history of SMA. The SMN1 protein has been associated with the assembly of spliceosomal ribonucleoproteins, which are critical to messenger RNA processing. The SMN1 protein has also been associated with the NAIP (neuronal apoptosis inhibitory protein) gene, a gene that helps to regulate programmed cell death. Some authors have hypothesized that a deletion of the SMN gene may be related to disturbances in the metabolism of 3',5'-adenosine monophosphate. Whether or not these disturbances contribute to neuronal degeneration in SMA remains to be seen.

A study by Sedghi et al indicated that deletions in exons 4 and 5 of NAIP are related to symptom severity in SMA. [18]