Which clinical history findings are characteristic of autosomal-recessive limb-girdle muscular dystrophy 2A (LGMD2A)

Updated: Aug 15, 2019
  • Author: Monica Saini, MD, MBBS, MRCP(UK); Chief Editor: Nicholas Lorenzo, MD, MHA, CPE  more...
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All patients have a history of progressive, proximal muscle weakness. Described below are the major distinguishing characteristics.

  • LGMD2A (calpainopathy; LGMDR1 Calpain-3; 15q15)

    • LGMD2A is likely the most common autosomal recessive LGMD, accounting for up to 30% of all recessive cases. In some areas, including the Basque region of Spain (where a founder mutation is identified), LGMD2A accounts for almost 80% of all cases of LGMD. In other areas, it is quite rare; for example, it accounts for only 6% of LGMD cases in Denmark.

    • Recently patients carrying a single pathogenic variant in the CAPN3 have been reported, indicating a proportion of dominant inheritance. [10]

    • About two thirds of patients present at 8–15 years of age (range of 2–40 years).

    • The most typical presentation is of symmetrical weakness due to scapular-humeral-pelvic weakness, which may be similar to the presentation of facioscapulohumeral dystrophy, but without facial weakness. LGMD2I may also have a similar phenotype.

    • Muscle weakness is predominant in the axial muscles of trunk and proximal lower limb. Hip-girdle weakness is most prominent in the gluteus maximus and hip adductors. Along with abdominal weakness, this leads to a wide-based, lordotic gait.

    • Relatively spared muscles include flexor carpi, triceps surae, tibialis posterior and anterior and the sternocleidomastoid.

    • The combination of scapular winging, severe weakness of hip adductors and elbow flexors, normal respiratory function, and contractures has specificity for LGMD2A. [11] Contractures are usually mild and predominate in the Achilles tendon.

    • Atrophy is often prominent.

    • Progression tends to be slow, and wheelchair use begins 11–28 years after the onset of symptoms. Men may show earlier onset and faster progression than women.

    • The clinical course varies widely among and within families. Age of onset and age at loss of independent ambulation varies between different mutations.

    • Atypical presentations include a severe Duchenne-like course, exercise-induced stiffness and myalgia before the onset of weakness, and early and clinically significant contractures (especially of the ankles, elbow, and neck) similar to those of Emery-Dreifuss muscular dystrophy.

    • Presentation with asymptomatic hyperCKemia has been reporte in up to 10% of cases.

    • Facial and cardiac involvement have not been reported.

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