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Muscular dystrophy, limb-girdle, autosomal dominant 4(LGMD1I; LGMDD4)

MedGen UID:
1648316
Concept ID:
C4748295
Disease or Syndrome
Synonym: MUSCULAR DYSTROPHY, LIMB-GIRDLE, TYPE 1I
SNOMED CT: Calpain-3-related limb girdle muscular dystrophy D4 (1279886003); Limb girdle muscular dystrophy type D4 (1279886003)
 
Gene (location): CAPN3 (15q15.1)
 
Monarch Initiative: MONDO:0029133
OMIM®: 618129

Definition

Autosomal dominant limb-girdle muscular dystrophy-4 (LGMDD4) is characterized by onset of proximal muscle weakness in young adulthood. Affected individuals often have gait difficulties; some may have upper limb involvement. Other features include variably increased serum creatine kinase, myalgia, and back pain. The severity and expressivity of the disorder is highly variable, even within families (summary by Vissing et al., 2016). For a discussion of genetic heterogeneity of autosomal dominant limb-girdle muscular dystrophy, see 603511. [from OMIM]

Clinical features

From HPO
Back pain
MedGen UID:
2530
Concept ID:
C0004604
Sign or Symptom
An unpleasant sensation characterized by physical discomfort (such as pricking, throbbing, or aching) localized to the back.
Myalgia
MedGen UID:
68541
Concept ID:
C0231528
Sign or Symptom
Pain in muscle.
Scapular winging
MedGen UID:
66822
Concept ID:
C0240953
Anatomical Abnormality
Abnormal protrusion of the scapula away from the surface of the back.
Gait disturbance
MedGen UID:
107895
Concept ID:
C0575081
Finding
The term gait disturbance can refer to any disruption of the ability to walk.
Hyperlordosis
MedGen UID:
9805
Concept ID:
C0024003
Finding
Abnormally increased curvature (anterior concavity) of the lumbar or cervical spine.
Myopathy
MedGen UID:
10135
Concept ID:
C0026848
Disease or Syndrome
A disorder of muscle unrelated to impairment of innervation or neuromuscular junction.
Proximal muscle weakness
MedGen UID:
113169
Concept ID:
C0221629
Finding
A lack of strength of the proximal muscles.
Muscle fiber splitting
MedGen UID:
322813
Concept ID:
C1836057
Finding
Fiber splitting or branching is a common finding in human and rat skeletal muscle pathology. Fiber splitting refers to longitudinal halving of the complete fiber, while branching originates from a regenerating end of a necrotic fiber as invaginations of the sarcolemma. In fiber branching, one end of the fiber remains intact as a single entity, while the other end has several branches.
Centrally nucleated skeletal muscle fibers
MedGen UID:
330782
Concept ID:
C1842170
Finding
An abnormality in which the nuclei of sarcomeres take on an abnormally central localization (or in which this feature is found in an increased proportion of muscle cells).
Increased variability in muscle fiber diameter
MedGen UID:
336019
Concept ID:
C1843700
Finding
An abnormally high degree of muscle fiber size variation. This phenotypic feature can be observed upon muscle biopsy.
Proximal amyotrophy
MedGen UID:
342591
Concept ID:
C1850794
Disease or Syndrome
Amyotrophy (muscular atrophy) affecting the proximal musculature.
Fatty replacement of skeletal muscle
MedGen UID:
866735
Concept ID:
C4021082
Finding
Muscle fibers degeneration resulting in fatty replacement of skeletal muscle fibers
Abdominal wall muscle weakness
MedGen UID:
867169
Concept ID:
C4021527
Finding
Decreased strength of the abdominal musculature.
Elevated circulating creatine kinase concentration
MedGen UID:
69128
Concept ID:
C0241005
Finding
An elevation of the level of the enzyme creatine kinase (also known as creatine phosphokinase (CK; EC 2.7.3.2) in the blood. CK levels can be elevated in a number of clinical disorders such as myocardial infarction, rhabdomyolysis, and muscular dystrophy.

Professional guidelines

PubMed

Chu ML, Moran E
Neurotherapeutics 2018 Oct;15(4):849-862. doi: 10.1007/s13311-018-0648-x. PMID: 30019308Free PMC Article

Recent clinical studies

Etiology

Aguti S, Gallus GN, Bianchi S, Salvatore S, Rubegni A, Berti G, Formichi P, De Stefano N, Malandrini A, Lopergolo D
Cells 2024 Feb 10;13(4) doi: 10.3390/cells13040329. PMID: 38391941Free PMC Article
Wang SC, Smith CD, Lombardo DM, Kimonis V
Neuromuscul Disord 2021 Aug;31(8):701-705. Epub 2021 Jun 12 doi: 10.1016/j.nmd.2021.06.005. PMID: 34244020
Chu ML, Moran E
Neurotherapeutics 2018 Oct;15(4):849-862. doi: 10.1007/s13311-018-0648-x. PMID: 30019308Free PMC Article
Broccolini A, Mirabella M
Biochim Biophys Acta 2015 Apr;1852(4):644-50. Epub 2014 Aug 19 doi: 10.1016/j.bbadis.2014.08.007. PMID: 25149037
Mitsuhashi S, Kang PB
Semin Pediatr Neurol 2012 Dec;19(4):211-8. doi: 10.1016/j.spen.2012.09.008. PMID: 23245554

Diagnosis

Mohan S, McNulty S, Thaxton C, Elnagheeb M, Owens E, Flowers M, Nunnery T, Self A, Palus B, Gorokhova S, Kennedy A, Niu Z, Johari M, Maiga AB, Macalalad K, Clause AR, Beckmann JS, Bronicki L, Cooper ST, Ganesh VS, Kang PB, Kesari A, Lek M, Levy J, Rufibach L, Savarese M, Spencer MJ, Straub V, Tasca G, Weihl CC
Ann Clin Transl Neurol 2024 Sep;11(9):2268-2276. Epub 2024 Aug 30 doi: 10.1002/acn3.52127. PMID: 39215466Free PMC Article
Aguti S, Gallus GN, Bianchi S, Salvatore S, Rubegni A, Berti G, Formichi P, De Stefano N, Malandrini A, Lopergolo D
Cells 2024 Feb 10;13(4) doi: 10.3390/cells13040329. PMID: 38391941Free PMC Article
Wang SC, Smith CD, Lombardo DM, Kimonis V
Neuromuscul Disord 2021 Aug;31(8):701-705. Epub 2021 Jun 12 doi: 10.1016/j.nmd.2021.06.005. PMID: 34244020
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
Mitsuhashi S, Kang PB
Semin Pediatr Neurol 2012 Dec;19(4):211-8. doi: 10.1016/j.spen.2012.09.008. PMID: 23245554

Therapy

Chu ML, Moran E
Neurotherapeutics 2018 Oct;15(4):849-862. doi: 10.1007/s13311-018-0648-x. PMID: 30019308Free PMC Article

Prognosis

Tang H, Xiong Y, Jiang K, Shen Y, Yu Y, Huang P, Zhu M, Li X, Zheng Y, Zhou M, Yu J, Deng J, Wang Z, Hong D, Qiu Y, Tan D
Muscle Nerve 2024 Oct;70(4):744-752. Epub 2024 Jul 23 doi: 10.1002/mus.28200. PMID: 39044557
Banerji CRS, Cammish P, Evangelista T, Zammit PS, Straub V, Marini-Bettolo C
Neuromuscul Disord 2020 Apr;30(4):315-328. Epub 2020 Mar 12 doi: 10.1016/j.nmd.2020.03.001. PMID: 32327287
Rosales XQ, Moser SJ, Tran T, McCarthy B, Dunn N, Habib P, Simonetti OP, Mendell JR, Raman SV
J Cardiovasc Magn Reson 2011 Aug 4;13(1):39. doi: 10.1186/1532-429X-13-39. PMID: 21816046Free PMC Article
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Hum Mutat 2008 Feb;29(2):258-66. doi: 10.1002/humu.20642. PMID: 17994539
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Acta Neurol Scand 1996 Sep;94(3):177-89. doi: 10.1111/j.1600-0404.1996.tb07050.x. PMID: 8899051

Clinical prediction guides

Tang H, Xiong Y, Jiang K, Shen Y, Yu Y, Huang P, Zhu M, Li X, Zheng Y, Zhou M, Yu J, Deng J, Wang Z, Hong D, Qiu Y, Tan D
Muscle Nerve 2024 Oct;70(4):744-752. Epub 2024 Jul 23 doi: 10.1002/mus.28200. PMID: 39044557
Valls A, Gutiérrez-Gutiérrez G, Martínez A, Ruiz-Roldán C, Camaño P, López de Munain A, Sáenz A
Muscle Nerve 2024 Apr;69(4):472-476. Epub 2024 Feb 1 doi: 10.1002/mus.28045. PMID: 38299438
Wang SC, Smith CD, Lombardo DM, Kimonis V
Neuromuscul Disord 2021 Aug;31(8):701-705. Epub 2021 Jun 12 doi: 10.1016/j.nmd.2021.06.005. PMID: 34244020
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
Vissing J, Barresi R, Witting N, Van Ghelue M, Gammelgaard L, Bindoff LA, Straub V, Lochmüller H, Hudson J, Wahl CM, Arnardottir S, Dahlbom K, Jonsrud C, Duno M
Brain 2016 Aug;139(Pt 8):2154-63. Epub 2016 Jun 3 doi: 10.1093/brain/aww133. PMID: 27259757

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