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Beggs AH1, Agrawal PB1.


GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2020.
2003 Mar 25 [updated 2013 Jan 24].

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Program in Genomics and Division of Genetics, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts


NOTE: THIS PUBLICATION IS ARCHIVED. IT IS FOR HISTORICAL REFERENCE ONLY, AND THE INFORMATION MAY BE OUT OF DATE. CLINICAL CHARACTERISTICS: Multiminicore disease (MmD) is broadly classified into four groups: Classic form (75% of individuals). Moderate form, with hand involvement (<10%). Antenatal form, with arthrogryposis multiplex congenita (<10%). Ophthalmoplegic form (<10%). Onset of the classic form is usually congenital or early in childhood with neonatal hypotonia, delayed motor development, axial muscle weakness, scoliosis, and significant respiratory involvement (often with secondary cardiac impairment). Spinal rigidity of varying severity is present. DIAGNOSIS/TESTING: The diagnosis of MmD is based on the presence of multiple "minicores" visible on muscle biopsy using oxidative stains, clinical findings of static or slowly progressive weakness, and absence of findings diagnostic of other neuromuscular disorders. Pathogenic variants in SELENON (SEPN1) and RYR1 are known to cause 50% of MmD cases reported; further genetic heterogeneity is suggested, but no other candidate region or gene has been identified to date. MANAGEMENT: Treatment of manifestations: Respiratory support as needed; aggressive treatment of lower respiratory infections; nasogastric feeding and high caloric density formulas as needed; physical and occupational therapy to improve/maintain gross and fine motor function and reduce joint contractures; speech therapy as needed; orthopedic treatment of scoliosis. Prevention of secondary complications: Yearly influenza and other respiratory infection-related immunizations. Surveillance: Routine evaluations of: neuromuscular status to assess disease progression; respiratory function re the risk of insidious nocturnal hypoxia and sudden respiratory failure; cardiac status re the risk of cardiac impairment secondary to respiratory involvement; the spine for scoliosis particularly during childhood and adolescence. Agents/circumstances to avoid: Depolarizing muscle relaxants and inhalational agents during surgery or childbirth, as they can trigger malignant hyperthermia. GENETIC COUNSELING: MmD is most often inherited in an autosomal recessive manner. The occurrence of MMD in two generations in a few families has been reported, suggestive of autosomal dominant inheritance. Assuming autosomal recessive inheritance, each sib of an affected individual has at conception a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Carrier testing for at-risk relatives and prenatal testing for pregnancies at increased risk are possible if the pathogenic variants in the family have been identified.

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