Details of Disease

General Information of Disease (ID: DIS39ELI)

• Disease Name: Congenital multicore myopathy with external ophthalmoplegia
• Synonyms: multiminicore disease with external ophthalmoplegia; minicore myopathy; minicore myopathy with external ophthalmoplegia; multicore myopathy; multicore myopathy with external ophthalmoplegia; multiminicore myopathy multicore myopathy with external ophthalmoplegia; minicore myopathy, antenatal onset, with arthrogryposis
• Definition: An autosomal recessive condition caused by mutation(s) in the RYR1 gene, encoding ryanodine receptor 1. It may be characterized clinically by neonatal hypotonia, delayed motor development, and generalized muscle weakness, and amyotrophy. Pathologically, the absence of mitochondria and focal disorganization of the sarcomere appear as "minicores" on ATPase staining as a result of focal defects in oxidative activity.
• Disease Hierarchy:
  DIS2BIP8: Congenital nervous system disorder
  DISIRF54: RYR1-related myopathy
  DISE6VYN: Multiminicore myopathy
  DIS39ELI: Congenital multicore myopathy with external ophthalmoplegia
• Disease Identifiers:
  MONDO ID: MONDO_0009712
  MESH ID: C564969
  UMLS CUI: C1850674
  OMIM ID: 255320
  MedGen ID: 340597
  Orphanet ID: 98905

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 3 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
RYR1	TTU5CIX	Limited	Genetic Variation	[1]
MYH7	TTNIMDP	Strong	Genetic Variation	[2]
RYR1	TTU5CIX	Definitive	Autosomal recessive	[3]

This Disease Is Related to 5 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
FXR1	OTEMQ1SR	Strong	Genetic Variation	[4]
MEGF10	OTILSPJ6	Strong	Genetic Variation	[5]
SELENON	OTSGKO5M	Strong	Genetic Variation	[6]
TRDN	OTXVE9SF	Strong	Biomarker	[7]
RYR1	OTWUB65S	Definitive	Autosomal recessive	[3]

References

• [1] Severe Neonatal RYR1 Myopathy With Pathological Features of Congenital Muscular Dystrophy.J Neuropathol Exp Neurol. 2019 Mar 1;78(3):283-287. doi: 10.1093/jnen/nlz004.
• [2] Mutations in MYH7 cause Multi-minicore Disease (MmD) with variable cardiac involvement.Neuromuscul Disord. 2012 Dec;22(12):1096-104. doi: 10.1016/j.nmd.2012.06.007. Epub 2012 Jul 10.
• [3] RYR1 mutations are a common cause of congenital myopathies with central nuclei. Ann Neurol. 2010 Nov;68(5):717-26. doi: 10.1002/ana.22119.
• [4] Recessive mutations in muscle-specific isoforms of FXR1 cause congenital multi-minicore myopathy.Nat Commun. 2019 Feb 15;10(1):797. doi: 10.1038/s41467-019-08548-9.
• [5] Adult-onset respiratory insufficiency, scoliosis, and distal joint hyperlaxity in patients with multiminicore disease due to novel Megf10 mutations.Muscle Nerve. 2016 Jun;53(6):984-8. doi: 10.1002/mus.25054. Epub 2016 Apr 25.
• [6] Aberrant regulation of epigenetic modifiers contributes to the pathogenesis in patients with selenoprotein N-related myopathies.Hum Mutat. 2019 Jul;40(7):962-974. doi: 10.1002/humu.23745. Epub 2019 Apr 1.
• [7] Abnormal distribution of calcium-handling proteins: a novel distinctive marker in core myopathies.J Neuropathol Exp Neurol. 2007 Jan;66(1):57-65. doi: 10.1097/NEN.0b013e31802d47ce.