Autosomal recessive limb-girdle muscular dystrophy type 2B

General Information (adopted from Orphanet):

Synonyms, Signs: LGMD3
LGMD2B
Muscular dystrophy, limb-girdle, type 3
Limb-girdle muscular dystrophy due to dysferlin deficiency
Number of Symptoms 28
OrphanetNr: 268
OMIM Id: 253601
ICD-10: G71.0
UMLs:
MeSH:
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence: < 0.9 of 100 000
Inheritance: Autosomal recessive
24843229 [IBIS]
Age of onset: Adolescent
Adult
23243261 [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 dysferlin
 -Rare genetic disease

Comment:

The levels of serum creatine kinase are reported to be higher in LGMD2B than in LGMD2A, indicating a more aggressive and active process of muscle wasting. The bi-articular muscles (gastrocnemius, semintendinosus, semimembranosus) involvement that occurs in LGMD2B could be explained by the fact that these muscle groups undergo shortening and lengthening cycles during exercise that causes active muscle regeneration–degeneration, but the failure of muscle repair due to dysferlin deficiency causes the failure to patch the membrane. The clinical progression appears to evolve more rapidly and homogenously in LGMD2B than in LGMD2A (PMID:20092694).

Symptom Information: Sort by abundance 

1
(HPO:0003713) Muscle fiber necrosis 20092694 IBIS 8 / 7739
2
(HPO:0003546) Exercise intolerance 20092694 IBIS 62 / 7739
3
(HPO:0003560) Muscular dystrophy 23243261 IBIS 88 / 7739
4
(HPO:0012664) Reduced ejection fraction 17828519 IBIS 32 / 7739
5
(HPO:0001644) Dilated cardiomyopathy 17828519 IBIS 141 / 7739
6
(HPO:0002792) Reduced vital capacity 23243261 IBIS 17 / 7739
7
(HPO:0011675) Arrhythmia Occasional [IBIS] 14% (n=22) 17994539 IBIS 226 / 7739
8
(HPO:0001712) Left ventricular hypertrophy Occasional [IBIS] 18% (n=22) 17994539 IBIS 76 / 7739
9
(HPO:0003236) Elevated serum creatine phosphokinase 20092694 IBIS 214 / 7739
10
(HPO:0003557) Increased variability in muscle fiber diameter 15201514 IBIS 24 / 7739
11
(HPO:0100295) Muscle fiber atrophy 24395438 IBIS 22 / 7739
12
(HPO:0003555) Muscle fiber splitting 20092694 IBIS 11 / 7739
13
(HPO:0008981) Calf muscle hypertrophy Rare [IBIS] 7.5% (n=40) 23243261 IBIS 28 / 7739
14
(HPO:0003458) EMG: myopathic abnormalities 24370491 IBIS 38 / 7739
15
(HPO:0003551) Difficulty climbing stairs 23243261 IBIS 23 / 7739
16
(HPO:0009046) Difficulty running 23243261 IBIS 17 / 7739
17
(HPO:0002072) Chorea Rare [IBIS] 2.5% (n=40) 23243261 IBIS 53 / 7739
18
(HPO:0003690) Limb muscle weakness 23243261 IBIS 41 / 7739
19
(HPO:0007340) Lower limb muscle weakness 23243261 IBIS 61 / 7739
20
(HPO:0003484) Upper limb muscle weakness 23243261 IBIS 19 / 7739
21
(HPO:0003701) Proximal muscle weakness 23243261 IBIS 105 / 7739
22
(HPO:0008948) Proximal upper limb amyotrophy 23243261 IBIS 3 / 7739
23
(HPO:0003691) Scapular winging Rare [IBIS] 2.5% (n=40) 23243261 IBIS 51 / 7739
24
(HPO:0003307) Hyperlordosis Rare [IBIS] 5% (n=40) 23243261 IBIS 122 / 7739
25
(HPO:0003306) Spinal rigidity Rare [IBIS] 2.5% (n=40) 23243261 IBIS 30 / 7739
26
(HPO:0100515) Pollakisuria Rare [IBIS] 2.5% (n=40) 23243261 IBIS 12 / 7739
27
(HPO:0009025) Increased connective tissue 22057634 IBIS 11 / 7739
28
(HPO:0003677) Slow progression 15201514 IBIS 134 / 7739

Associated genes:

DYSF;

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Diagnosis OMIM Cacciottolo et al. (2011) found that all of 55 patients with an undetermined LGMD clinical phenotype and 10 patients with a Miyoshi myopathy phenotype who had less than 20% dysferlin on skeletal muscle biopsy determined by Western blot ...
Clinical Description OMIM Bashir et al. (1994) reported 2 unrelated consanguineous families, 1 of Palestinian and 1 of Sicilian origin, with autosomal recessive LGMD. Age at onset ranged from 15 to 25 years with difficulty in climbing stairs, fatigue, weakness, and ...
Molecular genetics OMIM In affected members of 8 Libyan Jewish families with LGMD2B, Bashir et al. (1998) identified a homozygous mutation in the DYSF gene (603009.0005). In a ninth Libyan Jewish family, with a single affected member, the mutation was detected ...
Population genetics OMIM Guglieri et al. (2008) found that LGMD2B was the second most common form of LGMD after LGMD2A among 155 Italian probands. LGMD2B occurred in 18.7% of probands, whereas LGMD2A occurred in 28.4%. In LGMD2B, there was a correlation ...