Rigid Spine Muscular Dystrophy 1

Alternative Names

  • RSMD1
  • Rigid Spine Syndrome
  • RSS
  • Myopathy, SEPN1-Related
  • Muscular Dystrophy, Congenital, Merosin-Positive, with Early Spine Rigidity
  • MDRS1
  • Multicore Myopathy, Severe Classic Form
  • Minicore Myopathy, Severe Classic Form
  • Multiminicore Disease, Severe Classic Form
  • Desmin-Related Myopathy with Mallory Bodies
  • Muscular Dystrophy, Congenital, Eichsfeld Type
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WHO-ICD-10 version:2010

Diseases of the nervous system

Diseases of myoneural junction and muscle

OMIM Number

602771

Mode of Inheritance

Autosomal recessive

Gene Map Locus

1p36.11

Description

Minicore myopathy is a rare form of congenital myopathy, characterized by the presence of multiple minicores at the periphery of muscle fibers. Clinically, it is a heterogeneous disorder, with four major sub-groups being recognized. Over 75% of patients display the 'classic' form of the disease. This form presents in the neonatal period, and is characterized by marked hypotonia with weakness, delayed motor development, joint hyperextensibility, and poor head control. The muscle weakness is predominantly axial, with the neck flexors being the most affected. Distal muscles are less affected, and there is no sensory loss. The weak axial muscles commonly lead to spinal rigidity and curvature, which can in turn, lead to progressive respiratory insufficiency. Rigid spine syndrome (RSS) and the severe classic form of multiminicore disease, thus are part of the same entity. The course of the disease is rapid during adolescence, but becomes stable in adulthood.

The condition is diagnosed on the basis of the clinical features along with a muscle biopsy, which typically shows an excess of type I fibers, and the presence of the minicores. These cores represent areas of loss of mitochondrial activity and sarcomeric disorganization. Fetal movements have been noticed to be reduced in about 30% of the cases. There is no treatment for the condition. Management strategies include physiotherapy, exercise, and corrective spinal surgery, if needed. Breathing problems might require ventilation support. Feeding tubes might also be required in certain cases.

Molecular Genetics

Multiminicore disease is transmitted in an autosomal recessive fashion. This is corroborated by the presence of the disease in several consanguineous families worldwide and the absence of any clearly documented cases of autosomal dominant transmission. About half of all cases of the classic form are caused by mutations in the SEPN1 gene, which spans a length of about 18kb on the short arm of chromosome 1. This gene codes for Selenoprotein N, a 66 kDa glycoprotein localized in the endoplasmic reticulum and belonging to a family of proteins known for their involvement in various antioxidant defense systems as well as in several diverse metabolic pathways. The protein shows abundant expression in the fetal muscle precursor cells, indicating a role in myogenesis. More than 30 mutations in the SEPN1 gene have been implicated in about 50% of all cases of multiminicore disease or spinal rigidity syndrome.

Epidemiology in the Arab World

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Other Reports

Kuwait

Al-Jumah et al. (2004) reported, what they believed to be, the first reported cases of multiminicore disease in the Middle East. The five patients in this study belonged to two separate families. The first family had two affected boys born to non-consanguineous healthy parents. Both, seen at ages 9- and 10-years, presented with delays in motor development milestones, generalized hypotonia, muscle weakness, which was more at the proximal than at distal ends, absent deep tendon reflexes, and drooping of shoulders. Muscle biopsy performed in the older brother showed increase in fibrosis, variation in fiber size, type I fibre predominance, and the presence of central and eccentric cores. The condition in this family remained non-progressive. The second family consisted of three affected members born to consanguineous healthy parents. The proband was first seen at the age of 7-years, at which time he presented with relatively minor motor difficulties. He had hypotonia with weakness in all limbs and preserved deep tendon reflexes. By the age of 12-years, the condition had worsened such that he was unable to walk, had hyporeflexia, more proximal weakness, and wasting of the interossei muscles. He had also developed a chronic cough, and pulmonary function tests showed evidence of restrictive airway disease. Muscle biopsy results were compatible with that of multiminocore disease. A younger sister and brother of the proband showed similar course of progression of the disease, with respiratory problems and scoliosis developing.

Morocco

Niamane et al. (1999) reported two cases diagnosed with rigid spine syndrome. The first patient was a 12-year-old boy diagnosed at three years of age with Duchenne's muscular dystrophy because of delayed onset of walking. However, a more current evaluation indicated the presence of contracture of the Achilles tendons, flexion contracture of the elbows, and loss of motion of the cervical. Radiographs of the affected joints were normal. An electrocardiogram showed an incomplete left bundle branch block. Muscle enzyme activities were moderately elevated. A myopathic pattern was seen on the electromyogram. A muscle biopsy showed muscle fiber atrophy with peri- and endomysial fibrosis. The second patient was a 39-year-old man with a five-year history of isolated rigidity of the cervical spine thought to be due to a spondylarthropathy. Extension was the only movement possible at the cervical spine. The peripheral joints showed no motion range limitation. Findings were normal from radiographs of the spine and sacroiliac joints, an erythrocyte sedimentation rate determination, an electromyogram, and muscle enzyme activity assays. A muscle biopsy showed muscle fiber atrophy with peri- and endomysial fibrosis.

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