Autosomal recessive limb girdle muscular dystrophy type 2A

General Information (adopted from Orphanet):

Synonyms, Signs: LGMD2
Muscular dystrophy, pelvofemoral
Limb girdle muscular dystrophy due to calpain deficiency
calpainopathy myositis, eosinophilic, included
muscular dystrophy, limb-girdle, type 2
Leyden-Moebius muscular dystrophy
Primary calpainopathy
Number of Symptoms 19
OrphanetNr: 267
OMIM Id: 253600
ICD-10: G71.0

Prevalence, inheritance and age of onset:

Prevalence: < 9 of 100 000
Inheritance: Autosomal recessive
24843229 [IBIS]
Age of onset: Childhood
24843229 [IBIS]

Disease classification (adopted from Orphanet):

Parent Diseases: Autosomal recessive limb-girdle muscular dystrophy
 -Rare genetic disease
 -Rare neurologic disease
Qualitative or quantitative defects of calpain
 -Rare genetic disease


Limb-girdle muscular dystrophy type 2A is one of the most frequent subtypes of autosomal recessive muscular dystrophy, accounting for up to 30% of all recessive LGMD cases taken together. Pathogenic CAPN3 mutations disrupt multiple homeostatic mechanisms in skeletal muscles, resulting in LGMD2A. Patients carrying two null mutations that result in the premature truncation of protein synthesis are invariably characterized by a higher disease severity than patients with at least one missense mutation. (PMID:27081656).

Symptom Information: Sort by abundance 

(HPO:0012663) Mildly reduced ejection fraction Occasional [IBIS] 27081656 IBIS 4 / 7739
(HPO:0001962) Palpitations Rare [IBIS] 27081656 IBIS 62 / 7739
(HPO:0003236) Elevated serum creatine phosphokinase 19364062 IBIS 214 / 7739
(HPO:0001880) Eosinophilia 21204801 IBIS 35 / 7739
(HPO:0003797) Limb-girdle muscle atrophy Very frequent [IBIS] 23414389 IBIS 8 / 7739
(HPO:0007126) Proximal amyotrophy 27081656 IBIS 29 / 7739
(HPO:0008981) Calf muscle hypertrophy Rare [IBIS] 17994539 IBIS 28 / 7739
(HPO:0003560) Muscular dystrophy 27081656 IBIS 88 / 7739
(HPO:0003198) Myopathy 27081656 IBIS 151 / 7739
(HPO:0002355) Difficulty walking 27081656 IBIS 61 / 7739
(HPO:0001324) Muscle weakness 27081656 IBIS 859 / 7739
(HPO:0003327) Axial muscle weakness 27081656 IBIS 10 / 7739
(HPO:0003325) Limb-girdle muscle weakness Very frequent [IBIS] 17994539 IBIS 22 / 7739
(HPO:0008994) Proximal muscle weakness in lower limbs 27081656 IBIS 11 / 7739
(HPO:0003691) Scapular winging Occasional [IBIS] 27081656 IBIS 51 / 7739
(HPO:0003307) Hyperlordosis 19364062 IBIS 122 / 7739
(HPO:0001371) Flexion contracture Frequent [IBIS] 27081656 IBIS 220 / 7739
(HPO:0002792) Reduced vital capacity 27081656 IBIS 17 / 7739
(HPO:0040083) Toe walking 19364062 IBIS 15 / 7739

Associated genes:


ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Description: (OMIM) LGMD2A is an autosomal recessive form of muscular dystrophy primarily affecting the proximal muscles, resulting in difficulty walking. The age at onset varies, but most patients show onset in childhood, and the disorder is progressive. Other features may ...
Diagnosis OMIM Among 58 patients with LGMD2A confirmed by mutation analysis, Fanin et al. (2004) found that 46 (80%) had a variable degree of calpain-3 protein deficiency determined by immunoblot analysis, and 12 (20%) had normal amounts of calpain-3. The ...
Clinical Description OMIM In a large study of patients with different forms of muscular dystrophy, Chung and Morton (1959) delineated the common features of limb-girdle muscular dystrophy. Onset usually occurred in childhood, but sometimes in maturity or middle age. Involvement was ...
Molecular genetics OMIM In families with LGMD2 linked to chromosome 15, Richard et al. (1995) identified mutations in the calpain-3 gene; in all, 15 nonsense, splice site, frameshift, or missense calpain-3 mutations were found to segregate with the disease. Six of ...
Population genetics OMIM Pfaendler (1950) reported an affected Swiss pedigree which was studied further by Touraine (1955). Jackson and Carey (1961) found the same type of autosomal recessive muscular dystrophy in the descendants of Swiss immigrants in an Amish isolate in ...
Diagnosis GeneReviews Calpainopathy (also known as limb-girdle muscular dystrophy 2A, or LGMD2A) is suspected in individuals with the following:...
Clinical Description GeneReviews Calpainopathy is characterized by symmetric and progressive weakness of proximal (limb-girdle) muscles. The age at onset of muscle weakness ranges from two to 40 years. Early motor milestones are usually normal. Intra- and interfamilial clinical variability ranges from severe to mild [Richard et al 1999]. ...
Genotype-Phenotype Correlations GeneReviews Genotype-phenotype correlation in calpainopathy is complex and often complicated by the fact that most individuals are compound heterozygotes for CAPN3 mutations. ...
Differential Diagnosis GeneReviews Other forms of autosomal recessive limb-girdle muscular dystrophy (LGMD2) (i.e., LGMD2B – LGMD2L) cannot be distinguished from calpainopathy on clinical grounds, although calpainopathy generally has a later onset and is relatively mild, particularly by comparison with sarcoglycanopathies. Immunoblot analysis of muscle biopsy for candidate proteins (sarcoglycans, dysferlin, telethonin, titin) can help establish the correct diagnosis. (See Limb-Girdle Muscular Dystrophy Overview.) ...
Management GeneReviews To establish the extent of disease in an individual diagnosed with calpainopathy, a complete physical evaluation including the grading of muscle strength in single muscles and the analysis of several functional performances is recommended. ...
Molecular genetics GeneReviews Information in the Molecular Genetics and OMIM tables may differ from that elsewhere in the GeneReview: tables may contain more recent information. —ED....