What causes congenital muscular dystrophy (CMD) with rigid spine?

Updated: Jul 03, 2019
  • Author: Emad R Noor, MBChB; Chief Editor: Amy Kao, MD  more...
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This is an autosomal recessive disease due to a mutation in the selenoprotein N gene (SEPN1).

Selenoprotein N is a ubiquitously expressed glycoprotein that localizes to the endoplasmic reticulum and has an unknown function, but it is involved in oxidation/reduction reactions.

Increased levels are present in myoblasts, with lower levels in myotubes or mature muscle fibers. This finding suggests a role in early muscle development or in muscle cell proliferation or regeneration.

Mutations in selenoprotein N also cause multiminicore disease, congenital myopathy with desmin inclusions, and a congenital fiber type size disproportion related syndrome.

  • The term SEPN -related myopathy has been proposed to classify all of these diseases, in part because different mutations in the same gene may cause more than 1 muscle biopsy phenotype. However, there is considerable clinical phenotypic overlap with congenital or early-onset hypotonia, predominantly affected axial musculature leading to poor head control and scoliosis, and prominent respiratory insufficiency. [16]

  • The axial muscles share the property of being tonically contracted to maintain posture and suggest a possible specific mechanical constraint related to selenoprotein N cellular function.

A mutation in selenocysteine insertion sequence-binding protein 2 leads to multisystem selenoprotein deficiency (including selenoprotein N) that causes an axial muscular dystrophy similar to that caused by mutation in SEPN1, as well as resulting in azoospermia, impaired T-lymphocyte proliferation, abnormal mononuclear cell cytokine secretion, telomere shortening, and photosensitivity. [17]

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