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Myopathy, distal, 4(MPD4)

MedGen UID:
481352
Concept ID:
C3279722
Disease or Syndrome
Synonyms: MPD4; WILLIAMS DISTAL MYOPATHY
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Sources: HPO, OMIM
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
 
Gene (location): FLNC (7q32.1)
 
Monarch Initiative: MONDO:0013550
OMIM®: 614065
Orphanet: ORPHA63273

Definition

Williams distal myopathy is an autosomal dominant slowly progressive muscular disorder characterized by distal muscle weakness and atrophy affecting the upper and lower limbs. Onset occurs around the third to fourth decades of life, and patients remain ambulatory even after long disease duration. Muscle biopsy shows nonspecific changes with no evidence of rods, necrosis, or inflammation (summary by Duff et al., 2011). Mutation in the FLNC gene can also cause myofibrillar myopathy-5 (MFM5; 609524), which shows a different pattern of muscle involvement and different histologic changes. [from OMIM]

Clinical features

From HPO
Distal upper limb amyotrophy
MedGen UID:
867223
Concept ID:
C4021581
Disease or Syndrome
Muscular atrophy of distal arm muscles.
Abnormality of the calf musculature
MedGen UID:
867409
Concept ID:
C4021779
Anatomical Abnormality
Cardiomyopathy
MedGen UID:
209232
Concept ID:
C0878544
Disease or Syndrome
A disease of the heart muscle or myocardium proper. Cardiomyopathies may be classified as either primary or secondary, on the basis of etiology, or on the pathophysiology of the lesion: hypertrophic, dilated, or restrictive.
Hyporeflexia
MedGen UID:
195967
Concept ID:
C0700078
Finding
Reduction of neurologic reflexes such as the knee-jerk reaction.
Myopathy
MedGen UID:
10135
Concept ID:
C0026848
Disease or Syndrome
A disorder of muscle unrelated to impairment of innervation or neuromuscular junction.
Muscle weakness
MedGen UID:
57735
Concept ID:
C0151786
Finding
A reduction in the strength of one or more muscles.
Proximal muscle weakness
MedGen UID:
113169
Concept ID:
C0221629
Finding
A lack of strength of the proximal muscles.
Skeletal muscle atrophy
MedGen UID:
892680
Concept ID:
C0541794
Pathologic Function
The presence of skeletal muscular atrophy (which is also known as amyotrophy).
Distal lower limb amyotrophy
MedGen UID:
324515
Concept ID:
C1836451
Disease or Syndrome
Muscular atrophy of distal leg muscles.
Distal upper limb amyotrophy
MedGen UID:
867223
Concept ID:
C4021581
Disease or Syndrome
Muscular atrophy of distal arm muscles.
Abnormality of the calf musculature
MedGen UID:
867409
Concept ID:
C4021779
Anatomical Abnormality
Mildly elevated creatine kinase
MedGen UID:
342469
Concept ID:
C1850309
Finding

Recent clinical studies

Etiology

Yu M, Zhu Y, Lu Y, Lv H, Zhang W, Yuan Y, Wang Z
Orphanet J Rare Dis 2020 Dec 9;15(1):344. doi: 10.1186/s13023-020-01626-y. PMID: 33298082Free PMC Article
Nahari Y, Abbas A, Curtis E, Jacob S
BMJ Case Rep 2019 Apr 3;12(4) doi: 10.1136/bcr-2018-226903. PMID: 30948392Free PMC Article
Cho A, Hayashi YK, Monma K, Oya Y, Noguchi S, Nonaka I, Nishino I
J Neurol Neurosurg Psychiatry 2014 Aug;85(8):914-7. Epub 2013 Sep 11 doi: 10.1136/jnnp-2013-305587. PMID: 24027297
Pénisson-Besnier I
Rev Neurol (Paris) 2013 Aug-Sep;169(8-9):534-45. Epub 2013 Sep 3 doi: 10.1016/j.neurol.2012.09.021. PMID: 24008050
Mori-Yoshimura M, Oya Y, Hayashi YK, Noguchi S, Nishino I, Murata M
Neuromuscul Disord 2013 Jan;23(1):84-8. Epub 2012 Nov 2 doi: 10.1016/j.nmd.2012.09.007. PMID: 23127962

Diagnosis

Savarese M, Sarparanta J, Vihola A, Jonson PH, Johari M, Rusanen S, Hackman P, Udd B
Acta Myol 2020 Dec;39(4):245-265. Epub 2020 Dec 1 doi: 10.36185/2532-1900-028. PMID: 33458580Free PMC Article
Yu M, Zhu Y, Lu Y, Lv H, Zhang W, Yuan Y, Wang Z
Orphanet J Rare Dis 2020 Dec 9;15(1):344. doi: 10.1186/s13023-020-01626-y. PMID: 33298082Free PMC Article
Mishra SK, Valles-Ayoub Y, Darvish D, Khosa S, Moheb N, Trikamji B, Rafiei N, Freundlich R
J Clin Neuromuscul Dis 2019 Jun;20(4):210-213. doi: 10.1097/CND.0000000000000231. PMID: 31135625
Nahari Y, Abbas A, Curtis E, Jacob S
BMJ Case Rep 2019 Apr 3;12(4) doi: 10.1136/bcr-2018-226903. PMID: 30948392Free PMC Article
Pénisson-Besnier I
Rev Neurol (Paris) 2013 Aug-Sep;169(8-9):534-45. Epub 2013 Sep 3 doi: 10.1016/j.neurol.2012.09.021. PMID: 24008050

Therapy

Lochmüller H, Behin A, Tournev I, Tarnopolsky M, Horváth R, Pogoryelova O, Shah J, Koutsoukos T, Skrinar A, Kakkis E, Bedrosian CL, Mozaffar T
J Neuromuscul Dis 2021;8(2):225-234. doi: 10.3233/JND-200565. PMID: 33459658Free PMC Article
Elahi B, Laughlin RS, Litchy WJ, Milone M, Liewluck T
Muscle Nerve 2019 Apr;59(4):475-478. Epub 2019 Jan 6 doi: 10.1002/mus.26393. PMID: 30536954
Mayhew J, Bonner N, Arbuckle R, Turnbull A, Bowden A, Skrinar A
J Comp Eff Res 2018 Apr;7(4):381-395. Epub 2017 Nov 15 doi: 10.2217/cer-2017-0062. PMID: 29139300
Nishino I, Carrillo-Carrasco N, Argov Z
J Neurol Neurosurg Psychiatry 2015 Apr;86(4):385-92. Epub 2014 Jul 7 doi: 10.1136/jnnp-2013-307051. PMID: 25002140Free PMC Article
Rider LG, Shah M, Mamyrova G, Huber AM, Rice MM, Targoff IN, Miller FW; Childhood Myositis Heterogeneity Collaborative Study Group.
Medicine (Baltimore) 2013 Jul;92(4):223-243. doi: 10.1097/MD.0b013e31829d08f9. PMID: 23877355Free PMC Article

Prognosis

Tarnopolsky MA, Hatcher E, Shupak R
Can J Neurol Sci 2016 May;43(3):381-4. Epub 2016 Feb 25 doi: 10.1017/cjn.2015.386. PMID: 26911292
Chamova T, Guergueltcheva V, Gospodinova M, Krause S, Cirak S, Kaprelyan A, Angelova L, Mihaylova V, Bichev S, Chandler D, Naydenov E, Grudkova M, Djukmedzhiev P, Voit T, Pogoryelova O, Lochmüller H, Goebel HH, Bahlo M, Kalaydjieva L, Tournev I
Neuromuscul Disord 2015 Sep;25(9):713-8. Epub 2015 Jul 13 doi: 10.1016/j.nmd.2015.07.004. PMID: 26231298
Celeste FV, Vilboux T, Ciccone C, de Dios JK, Malicdan MC, Leoyklang P, McKew JC, Gahl WA, Carrillo-Carrasco N, Huizing M
Hum Mutat 2014 Aug;35(8):915-26. doi: 10.1002/humu.22583. PMID: 24796702Free PMC Article
Cho A, Hayashi YK, Monma K, Oya Y, Noguchi S, Nonaka I, Nishino I
J Neurol Neurosurg Psychiatry 2014 Aug;85(8):914-7. Epub 2013 Sep 11 doi: 10.1136/jnnp-2013-305587. PMID: 24027297
Linssen WH, de Voogt WG, Krahn M, Bernard R, Levy N, Wokke JH, Ginjaar HB, de Visser M
Eur J Neurol 2013 Jun;20(6):968-74. Epub 2013 Mar 26 doi: 10.1111/ene.12129. PMID: 23530687

Clinical prediction guides

Lochmüller H, Behin A, Tournev I, Tarnopolsky M, Horváth R, Pogoryelova O, Shah J, Koutsoukos T, Skrinar A, Kakkis E, Bedrosian CL, Mozaffar T
J Neuromuscul Dis 2021;8(2):225-234. doi: 10.3233/JND-200565. PMID: 33459658Free PMC Article
Yoshioka W, Miyasaka N, Okubo R, Shimizu R, Takahashi Y, Oda Y, Nishino I, Nakamura H, Mori-Yoshimura M
Orphanet J Rare Dis 2020 Sep 11;15(1):245. doi: 10.1186/s13023-020-01487-5. PMID: 32917266Free PMC Article
Nicolau S, Liewluck T, Milone M
Muscle Nerve 2020 Oct;62(4):445-454. Epub 2020 Jun 1 doi: 10.1002/mus.26914. PMID: 32478919
Celeste FV, Vilboux T, Ciccone C, de Dios JK, Malicdan MC, Leoyklang P, McKew JC, Gahl WA, Carrillo-Carrasco N, Huizing M
Hum Mutat 2014 Aug;35(8):915-26. doi: 10.1002/humu.22583. PMID: 24796702Free PMC Article
Cho A, Hayashi YK, Monma K, Oya Y, Noguchi S, Nonaka I, Nishino I
J Neurol Neurosurg Psychiatry 2014 Aug;85(8):914-7. Epub 2013 Sep 11 doi: 10.1136/jnnp-2013-305587. PMID: 24027297

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