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Limb-girdle muscular dystrophy, type 1A(LGMD1A)

MedGen UID:
331802
Concept ID:
C1834659
Disease or Syndrome
Synonyms: LGMD1A; Muscular dystrophy, proximal, type 1A
Modes of inheritance:
Heterogeneous
MedGen UID:
5539
Concept ID:
C0019409
Qualitative Concept
Made up of elements or ingredients that are not alike.
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Autosomal dominant inheritance refers to genetic conditions that occur when a mutation is present in one copy of a given gene (i.e., the person is heterozygous).
 
Gene: MYOT
Cytogenetic location: 5q31.2
OMIM®: 159000
Orphanet: ORPHA266

Disease characteristics

Excerpted from the GeneReview: Limb-Girdle Muscular Dystrophy Overview
Limb-girdle muscular dystrophy (LGMD) is a purely descriptive term, generally reserved for childhood- or adult-onset muscular dystrophies that are distinct from the much more common X-linked dystrophinopathies. LGMDs are typically nonsyndromic, with clinical involvement typically limited to skeletal muscle. Individuals with LGMD generally show weakness and wasting restricted to the limb musculature, proximal greater than distal, and muscle degeneration/regeneration on muscle biopsy. Most individuals with LGMD show relative sparing of the bulbar muscles, although exceptions occur, depending on the genetic subtype. Onset, progression, and distribution of the weakness and wasting vary considerably among individuals and genetic subtypes. [from GeneReviews]
Full text of GeneReview (by section):
Summary  |  Definition  |  Causes  |  Evaluation Strategy  |  Genetic Counseling  |  Resources  |  Management  |  References  |  Chapter Notes
Authors:
Elena Pegoraro  |  Eric P Hoffman   view full author information

Additional descriptions

From OMIM
LGMD1 is an autosomal dominant disorder characterized by adult onset of proximal muscle weakness, beginning in the hip girdle region and later progressing to the shoulder girdle region. Distal muscle weakness may occur later. Daniele et al. (2007) provided a review of therapeutic strategies in various forms of LGMD, including ongoing studies in gene therapy. Genetic Heterogeneity of Autosomal Dominant Limb-Girdle Muscular Dystrophy Other forms of autosomal dominant LGMD include LGMD1B (159001), caused by mutation in the LMNA gene (150330) on chromosome 1q21; LGMD1C (607801), caused by mutation in the CAV3 gene (601253) on chromosome 3p25; LGMD1E (603511), caused by mutation in the DNAJB6 gene (611332) on chromosome 7q36; LGMD1F (608423), caused by mutation in the TNPO3 gene (610032) on chromosome 7q32; LGMD1G (609115), which maps to chromosome 4q21; and LGMD1H (613530), which maps to chromosome 3p25-p23. The symbol LGMD1D was formerly used for a disorder later found to be the same as desmin-related myopathy (601419).  http://www.omim.org/entry/159000
From GHR
Limb-girdle muscular dystrophy is a term for a group of diseases that cause weakness and wasting of the muscles in the arms and legs. The muscles most affected are those closest to the body (proximal muscles), specifically the muscles of the shoulders, upper arms, pelvic area, and thighs. The severity, age of onset, and features of limb-girdle muscle dystrophy vary among the many subtypes of this condition and may be inconsistent even within the same family. Signs and symptoms may first appear at any age and generally worsen with time, although in some cases they remain mild. In the early stages of limb-girdle muscular dystrophy, affected individuals may have an unusual walking gait, such as waddling or walking on the balls of their feet, and may also have difficulty running. They may need to use their arms to press themselves up from a squatting position because of their weak thigh muscles. As the condition progresses, people with limb-girdle muscular dystrophy may eventually require wheelchair assistance. Muscle wasting may cause changes in posture or in the appearance of the shoulder, back, and arm. In particular, weak shoulder muscles tend to make the shoulder blades (scapulae) "stick out" from the back, a sign known as scapular winging. Affected individuals may also have an abnormally curved lower back (lordosis) or a spine that curves to the side (scoliosis). Some develop joint stiffness (contractures) that can restrict movement in their hips, knees, ankles, or elbows. Overgrowth (hypertrophy) of the calf muscles occurs in some people with limb-girdle muscular dystrophy. Weakening of the heart muscle (cardiomyopathy) occurs in some forms of limb-girdle muscular dystrophy. Some affected individuals experience mild to severe breathing problems related to the weakness of muscles needed for breathing. Intelligence is generally unaffected in limb-girdle muscular dystrophy; however, developmental delay and intellectual disability have been reported in rare forms of the disorder.  http://ghr.nlm.nih.gov/condition/limb-girdle-muscular-dystrophy

Clinical features

Hyporeflexia
MedGen UID:
101804
Concept ID:
C0151888
Finding
Absent Achilles reflex
MedGen UID:
108240
Concept ID:
C0558845
Finding
Nasal, dysarthic speech
MedGen UID:
331804
Concept ID:
C1834664
Finding
Achilles tendon contracture
MedGen UID:
98052
Concept ID:
C0410264
Disease or Syndrome
Elevated serum creatine phosphokinase
MedGen UID:
505493
Concept ID:
CN002923
Finding
An elevation of the level of the enzyme creatine kinase (also known as creatine phosphokinase, CPK; EC 2.7.3.2) in the blood. CPK levels can be elevated in a number of clinical disorders such as myocardial infarction, rhabdomyolysis, and muscular dystrophy.
Achilles tendon contracture
MedGen UID:
98052
Concept ID:
C0410264
Disease or Syndrome
Pelvic girdle muscle weakness
MedGen UID:
96534
Concept ID:
C0427064
Finding
Muscle fiber splitting
MedGen UID:
336005
Concept ID:
C1843640
Finding
Rimmed vacuoles
MedGen UID:
340089
Concept ID:
C1853932
Finding
Muscular dystrophy
MedGen UID:
351199
Concept ID:
C1864711
Finding
EMG: myopathic abnormalities
MedGen UID:
428350
Concept ID:
CN003118
Finding
The presence of abnormal electromyographic patterns indicative of myopathy, such as small-short polyphasic motor unit potentials.
Shoulder girdle muscle weakness
MedGen UID:
500959
Concept ID:
CN003201
Finding
The shoulder, or pectoral, girdle is composed of the clavicles and the scapulae. Shoulder-girdle weakness refers to lack of strength of the muscles attaching to these bones, that is, lack of strength of the muscles around the shoulders.
Late-onset distal muscle weakness
MedGen UID:
500969
Concept ID:
CN003440
Finding
Achilles tendon contracture
MedGen UID:
98052
Concept ID:
C0410264
Disease or Syndrome
Achilles tendon contracture
MedGen UID:
98052
Concept ID:
C0410264
Disease or Syndrome
Pelvic girdle muscle weakness
MedGen UID:
96534
Concept ID:
C0427064
Finding
Absent Achilles reflex
MedGen UID:
108240
Concept ID:
C0558845
Finding
Shoulder girdle muscle weakness
MedGen UID:
500959
Concept ID:
CN003201
Finding
The shoulder, or pectoral, girdle is composed of the clavicles and the scapulae. Shoulder-girdle weakness refers to lack of strength of the muscles attaching to these bones, that is, lack of strength of the muscles around the shoulders.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews

Recent clinical studies

Etiology

Gamez J, Armstrong J, Shatunov A, Selva-O'Callaghan A, Dominguez-Oronoz R, Ortega A, Goldfarb L, Ferrer I, Olivé M
J Neurol Sci 2009 Feb 15;277(1-2):167-71. Epub 2008 Nov 22 doi: 10.1016/j.jns.2008.10.019. [Epub ahead of print] PMID: 19027924Free PMC Article
Olivé M, Goldfarb LG, Shatunov A, Fischer D, Ferrer I
Brain 2005 Oct;128(Pt 10):2315-26. Epub 2005 Jun 9 doi: 10.1093/brain/awh576. [Epub ahead of print] PMID: 15947064
Navarro C, Teijeira S
Acta Myol 2003 May;22(1):11-4. PMID: 12966699
De Sandre-Giovannoli A, Chaouch M, Kozlov S, Vallat JM, Tazir M, Kassouri N, Szepetowski P, Hammadouche T, Vandenberghe A, Stewart CL, Grid D, Lévy N
Am J Hum Genet 2002 Mar;70(3):726-36. Epub 2002 Jan 17 doi: 10.1086/339274. [Epub ahead of print] PMID: 11799477Free PMC Article

Diagnosis

Schessl J, Bach E, Rost S, Feldkirchner S, Kubny C, Müller S, Hanisch FG, Kress W, Schoser B
Neurogenetics 2014 Aug;15(3):151-6. Epub 2014 Jun 14 doi: 10.1007/s10048-014-0410-4. [Epub ahead of print] PMID: 24928145
Marques J, Duarte ST, Costa S, Jacinto S, Oliveira J, Oliveira ME, Santos R, Bronze-da-Rocha E, Silvestre AR, Calado E, Evangelista T
Neuromuscul Disord 2014 May;24(5):419-24. Epub 2014 Jan 25 doi: 10.1016/j.nmd.2014.01.004. [Epub ahead of print] PMID: 24534542
Shalaby S, Mitsuhashi H, Matsuda C, Minami N, Noguchi S, Nonaka I, Nishino I, Hayashi YK
J Neuropathol Exp Neurol 2009 Jun;68(6):701-7. doi: 10.1097/NEN.0b013e3181a7f703. PMID: 19458539
Schröder R, Reimann J, Salmikangas P, Clemen CS, Hayashi YK, Nonaka I, Arahata K, Carpén O
Neuromuscul Disord 2003 Aug;13(6):451-5. PMID: 12899871
Ki CS, Hong JS, Jeong GY, Ahn KJ, Choi KM, Kim DK, Kim JW
J Hum Genet 2002;47(5):225-8. doi: 10.1007/s100380200029. PMID: 12032588

Therapy

Walter MC, Reilich P, Thiele S, Schessl J, Schreiber H, Reiners K, Kress W, Müller-Reible C, Vorgerd M, Urban P, Schrank B, Deschauer M, Schlotter-Weigel B, Kohnen R, Lochmüller H
Orphanet J Rare Dis 2013 Feb 14;8:26. doi: 10.1186/1750-1172-8-26. [Epub ahead of print] PMID: 23406536Free PMC Article
Salmikangas P, van der Ven PF, Lalowski M, Taivainen A, Zhao F, Suila H, Schröder R, Lappalainen P, Fürst DO, Carpén O
Hum Mol Genet 2003 Jan 15;12(2):189-203. PMID: 12499399

Prognosis

Walter MC, Reilich P, Thiele S, Schessl J, Schreiber H, Reiners K, Kress W, Müller-Reible C, Vorgerd M, Urban P, Schrank B, Deschauer M, Schlotter-Weigel B, Kohnen R, Lochmüller H
Orphanet J Rare Dis 2013 Feb 14;8:26. doi: 10.1186/1750-1172-8-26. [Epub ahead of print] PMID: 23406536Free PMC Article

Clinical prediction guides

Walter MC, Reilich P, Thiele S, Schessl J, Schreiber H, Reiners K, Kress W, Müller-Reible C, Vorgerd M, Urban P, Schrank B, Deschauer M, Schlotter-Weigel B, Kohnen R, Lochmüller H
Orphanet J Rare Dis 2013 Feb 14;8:26. doi: 10.1186/1750-1172-8-26. [Epub ahead of print] PMID: 23406536Free PMC Article
Shalaby S, Mitsuhashi H, Matsuda C, Minami N, Noguchi S, Nonaka I, Nishino I, Hayashi YK
J Neuropathol Exp Neurol 2009 Jun;68(6):701-7. doi: 10.1097/NEN.0b013e3181a7f703. PMID: 19458539
Rudenskaya GE, Polyakov AV, Tverskaya SM, Zaklyazminskaya EV, Chukhrova AL, Groznova OE, Ginter EK
Clin Genet 2008 Aug;74(2):127-33. Epub 2008 Jun 28 doi: 10.1111/j.1399-0004.2008.01045.x. [Epub ahead of print] PMID: 18564364
Olivé M, Goldfarb LG, Shatunov A, Fischer D, Ferrer I
Brain 2005 Oct;128(Pt 10):2315-26. Epub 2005 Jun 9 doi: 10.1093/brain/awh576. [Epub ahead of print] PMID: 15947064
Schröder R, Reimann J, Salmikangas P, Clemen CS, Hayashi YK, Nonaka I, Arahata K, Carpén O
Neuromuscul Disord 2003 Aug;13(6):451-5. PMID: 12899871

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