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The Genetics of Limb Girdle Muscular Dystrophy

written by: •edited by: Paul Arnold•updated: 1/29/2009

Limb girdle muscular dystrophy (LGMD) is a genetic condition, and the term encompasses several types of this progressive muscle weakening disorder. The condition can be inherited as autosomal dominant or recessive, or X-linked.

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    Limb girdle muscular dystrophy (LGMD) is a genetic condition that can be either childhood or adult onset. This condition can be inherited as autosomal dominant or recessive, or X-linked. In LGMD, proteins that are involved in the functioning of muscles are not properly formed. Therefore, a specific protein that is needed for proper muscle functioning is absent or defective. The absent or defective proteins that lead to LGMD are proteins associated with the sacrolemma and the contractile apparatus.

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    Limb Girdle Muscular Dystrophy Characteristics

    • Limb Girdle Muscular Dystrophy can be present in males or females
    • Childhood or adult onset
    • Can be inherited as autosomal recessive or dominant (less frequent), or X-linked.
    • Disability is likely within 20-30 years after disease onset

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    Autosomal Dominant Limb Girdle Muscular Dystrophy

    The autosomal dominant form of LGMD occurs commonly in adulthood and presents with muscle weakness and elevated levels of creatine kinase (CK). A person with this condition will typically show the following muscular dystrophy symptoms: developing proximal weaknesses in the shoulder, pelvic girdle, upper thighs, and upper arms along with distal weakness in the lower legs and feet, lower arms, and hands. Luckily, most people who have LGMD do not have problems with the muscles of the heart. The severity of the weaknesses and how quickly the disease develops will depend on the specific gene mutations. Therefore, visiting a genetic counselor and having genetic testing done is recommended.

    The autosomal dominant form of LGMD is less common than the autosomal recessive form. The genetics of the dominant and recessive forms result in different disease states of LGMD, and a person with autosomal dominant LGMD has a later onset and slower development of LGMD than those that have the autosomal recessive form. The elevated levels of creatine kinase are higher in the autosomal recessive form.

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    Causes of Limb Girdle Muscular Dystrophy

    Autosomal recessive form of LGMD:

    • Caused by mutations on chromosome 15 in the calpain-3 gene.
    • LGMD2B is caused by mutations on chromosome 2 in the dysferlin gene.
    • LGMD2C is caused by a mutation on chromosome 13 in the gamma-sarcoglycan gene.
    • LGMD2D is caused by a mutation on chromosome 17 in the alpha-sarcoglycan (adhalin) gene.
    • LGMD2E is caused by a mutation on chromosome 4 in the beta-sarcoglycan gene.
    • LGMD2F is caused by a mutation on chromosome 5 in the delta-sarcoglycan gene.
    • LGMD2G is caused by mutations on chromosome 17 in the telethonin gene.
    • LGMD2H is caused by mutations on chromosome 9 in the TRIM32 gene.
    • LGMD2I is caused by mutations on chromosome 19 in the FKRP gene.
    • LGMD2J is caused by mutations on chromosome 2 in the titin gene.
    • LGMD2K is caused by mutations on chromosome 9 in the protein O-mannosyltransferase 1 (POMT1) gene

    Autosomal-dominant form of LGMD:

    • LGMD1A is caused by mutations on chromosome 5 in the myotilin gene.
    • LGMD1B is caused by mutations on chromosome 1 in the lamin A/C gene.
    • LGMD1C is caused by mutations on chromosome 3 in the caveolin-3 gene.
    • LGMD1D has been linked to chromosome arm 7q.
    • LGMD1E (dilated cardiomyopathy with conduction defect and muscular dystrophy) has been linked to chromosomal region 6q23.
    • LGMD1F has been linked to chromosomal bands 7q32.1-32.2.
    • LGMD1G has been linked to chromosomal region 4p21.
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    Visiting a Genetic Counselor

    Since there are several causes and different forms of LGMD, visiting a genetic counselor to learn about the specific conditions and too see if genetic testing is available, could be useful. Currently there aren't any cures for muscular dystrophies, but the symptoms and their effects can be managed.

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