Details of Disease

General Information of Disease (ID: DISU9T2M)

• Disease Name: Congenital fiber-type disproportion myopathy
• Synonyms: congenital fibre type disproportion; congenital fiber type disproportion; myopathy, congenital with fiber-type disproportion; congenital fiber-type disproportion; congenital myopathy with fibre type disproportion; CFTDM; congenital myopathy with fiber type disproportion
• Definition: A rare genetic disorder caused by mutations in the TPM3, ACTA1, RYR1 or SEPN1 genes. It is inherited in an autosomal dominant or recessive pattern and rarely in an X-linked pattern. It manifests with myopathy throughout the body, particularly in the muscles of the shoulders, upper arms, hips, and thighs. Affected individuals may have contractures, lordosis, or scoliosis. In a minority of cases mild to severe breathing problems may occur.
• Disease Hierarchy:
  DISZ9JP4: Congenital structural myopathy
  DIS7PCBA: TPM2-related myopathy
  DISIRF54: RYR1-related myopathy
  DIS1FW68: TPM3-related myopathy
  DISU9T2M: Congenital fiber-type disproportion myopathy
• Disease Identifiers:
  MONDO ID: MONDO_0009711
  MESH ID: D020914
  UMLS CUI: C0546264
  OMIM ID: 255310
  MedGen ID: 108177
  Orphanet ID: 2020
  SNOMED CT ID: 240084007

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 7 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
MYH7	TTNIMDP	Limited	Genetic Variation	[1]
RYR1	TTU5CIX	Limited	Genetic Variation	[2]
MAP3K20	TTTUZ3O	Supportive	Autosomal dominant	[3]
DMPK	TTZQTY2	Strong	Biomarker	[4]
DNM2	TTVRA5G	Strong	Biomarker	[5]
MAP3K20	TTTUZ3O	Strong	Genetic Variation	[3]
MTM1	TTY2TCU	Strong	Biomarker	[5]

This Disease Is Related to 1 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
CHKB	DEHWR6V	Strong	Biomarker	[6]

This Disease Is Related to 19 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
ACTA1	OTOVGLPG	Supportive	Autosomal dominant	[7]
HACD1	OTEC7EP7	Supportive	Autosomal dominant	[8]
ITGA7	OTTBTAYW	Supportive	Autosomal dominant	[9]
MAP3K20	OT0ALMEG	Supportive	Autosomal dominant	[3]
MYL2	OT78PC0C	Supportive	Autosomal dominant	[10]
SELENON	OTSGKO5M	Supportive	Autosomal dominant	[7]
TPM2	OTA1L0P8	Supportive	Autosomal dominant	[11]
TPM3	OT5RU5G6	Moderate	Semidominant	[12]
B4GAT1	OT5NH9TD	Strong	Biomarker	[13]
BIN1	OTK8O0X8	Strong	Biomarker	[14]
FKRP	OTMUZ7GH	Strong	Biomarker	[15]
FKTN	OTQ9GCXL	Strong	Biomarker	[16]
LARGE1	OTUH7H9F	Strong	Biomarker	[17]
LMNA	OT3SG7ZR	Strong	Genetic Variation	[18]
MYH7B	OTCB2IJB	Strong	Genetic Variation	[9]
PHOX2B	OT3SFR2O	Strong	Genetic Variation	[19]
POMGNT1	OTBNOUZC	Strong	Biomarker	[15]
SPTBN4	OTAJAVP9	Strong	Biomarker	[20]
TMCO1	OTSME34W	Strong	Genetic Variation	[21]

References

• [1] MYH7 mutation associated with two phenotypes of myopathy.Neurol Sci. 2018 Feb;39(2):333-339. doi: 10.1007/s10072-017-3192-2. Epub 2017 Nov 24.
• [2] Ryanodine Receptor 1-Related Myopathies: Diagnostic and Therapeutic Approaches.Neurotherapeutics. 2018 Oct;15(4):885-899. doi: 10.1007/s13311-018-00677-1.
• [3] Recessive mutations in the kinase ZAK cause a congenital myopathy with fibre type disproportion. Brain. 2017 Jan;140(1):37-48. doi: 10.1093/brain/aww257. Epub 2016 Nov 5.
• [4] Congenital myotonic dystrophy can show congenital fiber type disproportion pathology.Acta Neuropathol. 2010 Apr;119(4):481-6. doi: 10.1007/s00401-010-0660-7. Epub 2010 Feb 24.
• [5] Centronuclear myopathy due to a de novo dominant mutation in the skeletal muscle ryanodine receptor (RYR1) gene.Neuromuscul Disord. 2007 Apr;17(4):338-45. doi: 10.1016/j.nmd.2007.01.016. Epub 2007 Mar 21.
• [6] A rostrocaudal muscular dystrophy caused by a defect in choline kinase beta, the first enzyme in phosphatidylcholine biosynthesis.J Biol Chem. 2006 Feb 24;281(8):4938-48. doi: 10.1074/jbc.M512578200. Epub 2005 Dec 21.
• [7] Congenital Fiber-Type Disproportion C RETIRED CHAPTER, FOR HISTORICAL REFERENCE ONLY. 2007 Jan 12 [updated 2013 Apr 11]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews(?) [Internet]. Seattle (WA): University of Washington, Seattle; 1993C2024.
• [8] Congenital myopathy is caused by mutation of HACD1. Hum Mol Genet. 2013 Dec 20;22(25):5229-36. doi: 10.1093/hmg/ddt380. Epub 2013 Aug 9.
• [9] Digenic mutational inheritance of the integrin alpha 7 and the myosin heavy chain 7B genes causes congenital myopathy with left ventricular non-compact cardiomyopathy. Orphanet J Rare Dis. 2013 Jun 21;8:91. doi: 10.1186/1750-1172-8-91.
• [10] Recessive MYL2 mutations cause infantile type I muscle fibre disease and cardiomyopathy. Brain. 2013 Jan;136(Pt 1):282-93. doi: 10.1093/brain/aws293.
• [11] Mutations in TPM2 and congenital fibre type disproportion. Neuromuscul Disord. 2012 Nov;22(11):955-8. doi: 10.1016/j.nmd.2012.06.002. Epub 2012 Jul 24.
• [12] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [13] Dystroglycan organizes axon guidance cue localization and axonal pathfinding.Neuron. 2012 Dec 6;76(5):931-44. doi: 10.1016/j.neuron.2012.10.009.
• [14] Mutations in amphiphysin 2 (BIN1) disrupt interaction with dynamin 2 and cause autosomal recessive centronuclear myopathy. Nat Genet. 2007 Sep;39(9):1134-9. doi: 10.1038/ng2086. Epub 2007 Aug 5.
• [15] Degree of Cajal-Retzius Cell Mislocalization Correlates with the Severity of Structural Brain Defects in Mouse Models of Dystroglycanopathy.Brain Pathol. 2016 Jul;26(4):465-78. doi: 10.1111/bpa.12306. Epub 2015 Oct 12.
• [16] Residual laminin-binding activity and enhanced dystroglycan glycosylation by LARGE in novel model mice to dystroglycanopathy.Hum Mol Genet. 2009 Feb 15;18(4):621-31. doi: 10.1093/hmg/ddn387. Epub 2008 Nov 18.
• [17] Ocular abnormalities in Large(myd) and Large(vls) mice, spontaneous models for muscle, eye, and brain diseases.Mol Cell Neurosci. 2005 Oct;30(2):160-72. doi: 10.1016/j.mcn.2005.07.009.
• [18] Muscle fiber type disproportion (FTD) in a family with mutations in the LMNA gene.Muscle Nerve. 2015 Apr;51(4):604-8. doi: 10.1002/mus.24467. Epub 2015 Feb 24.
• [19] Congenital muscle fiber-type disproportion in a patient with congenital central hypoventilation syndrome due to PHOX2B mutations.J Child Neurol. 2008 Jul;23(7):829-31. doi: 10.1177/0883073808314895.
• [20] A recessive mutation in beta-IV-spectrin (SPTBN4) associates with congenital myopathy, neuropathy, and central deafness.Hum Genet. 2017 Jul;136(7):903-910. doi: 10.1007/s00439-017-1814-7. Epub 2017 May 24.
• [21] A novel biallelic loss-of-function mutation in TMCO1 gene confirming and expanding the phenotype spectrum of cerebro-facio-thoracic dysplasia.Am J Med Genet A. 2019 Jul;179(7):1338-1345. doi: 10.1002/ajmg.a.61168. Epub 2019 May 18.