Subtypes of Limb-Girdle Muscular Dystrophy

Here's a look at the 26 subtypes of LGMD that have been recognized dating back to the 1990s

Article Highlights:

The subtypes of LGMD chart is part of the In Focus: Limb-Girdle Muscular Dystrophy package that appears in the October-December 2013 issue of Quest magazine.

The other articles included in this special series are:

by Quest Staff on October 3, 2013 - 9:09am

Quest Vol. 20, No. 4

 

Subtypes of Limb-Girdle Muscular Dystrophy
Subtype Gene/Protein Symptoms Inheritance
Bethlem myopathy mutations in COL6A1, COL6A2 or COLA3 gene, causing abnormalities in or deficiency of collagen 6 protein; protein normally plays a role in matrix onset between early childhood and 50s; joints can have contractures or be overly flexible; weakness usually mild in childhood, but may become severe in adulthood; respiratory muscle weakness in some; muscle cramps or pain in some; skin abnormalities; cardiac conduction dominant or recessive 
LGMD1A; also known as type 3 myofibrillar myopathy (MFM3) mutations in myotilin gene, causing abnormalities in myotilin protein; protein normally plays a role in sarcomere and muscle-fiber membrane onset in adulthood; weakness in proximal arm and leg muscles; may progress to distal muscles, such as those in wrists, fingers and ankles; some have neck and face weakness; some have respiratory involvement; 50 percent develop cardiomyopathy; 25 percent have muscle pain; ankle contractures in 30 percent; difficulty speaking in 30 percent dominant
LGMD1B mutations in lamin A/C gene, causing abnormalities in lamin A or lamin C proteins; these proteins normally form part of membrane around cell nucleus onset before age 20; weakness in proximal leg muscles; slow progression, with arms involved in 20s or 30s; no contractures; cardiomyopathy in 62 percent; cardiac conduction block can occur dominant
LGMD1C mutations in caveolin 3 gene, causing deficiency of or abnormalities in caveolin 3 protein; protein normally plays role in muscle-fiber membrane onset 5 years to adulthood; weakness; difficulty walking; moderate severity; cramps after exercise; cardiomyopathy; some have conduction abnormalities dominant or recessive
LGMD1D mutations in DNAJB6 gene, causing abnormalities in DNAJB6 protein; protein normally protects other proteins from forming clumps onset in 20s to 50s; weakness greater in legs than arms; slow progression; loss of walking ability after 20 to 30 years; difficulty swallowing in 20 percent dominant
LGMD1E; also known as myofibrillar myopathy 1 (MFM1) mutations in desmin gene, causing abnormalities in desmin protein; protein normally plays a role in sarcomere onset in teens or later; weakness; slow progression; walking ability maintained; cardiac rhythm abnormalities; heart enlargement; found in one large family of French-Canadian descent dominant
LGMD1F mutations in transportin gene, causing abnormalities in transportin 3 protein; protein normally helps transport substances into the cell nucleus found in one Spanish family; onset 1 to 58 years; proximal leg weakness early; distal leg weakness later; arm weakness; some have respiratory muscle weakness; some stop walking in teens or 20s; some have ankle contractures; some develop spinal curvatures dominant
LGMD1G mutations in unidentified gene on chromosome 4, causing abnormalities in unidentified protein found in one Brazilian family; onset 30 to 47 years; leg weakness, leg cramps; arm weakness; limited ability to flex fingers and toes dominant
LGMD1H mutations in unidentified gene on chromosome 3, causing abnormalities in unidentified protein found in one Italian family; onset ages 16 to 50; arm and leg weakness; more severe with younger onset dominant
LGMD2A mutations in calpain 3 gene, causing deficiency of calpain 3 protein; protein thought to play a role in muscle-fiber membrane repair and remodeling onset 2 to 45 years, with most between 6 and 18 years; starts with weakness of upper legs and abdominal muscles; may progress to generalized weakness, including shoulder and arm muscles; respiratory capacity declines somewhat over time; lordosis ("swayback"); loss of walking in teens or 20s on average; joint contractures; spine may develop rigidity; normal intelligence or mild intellectual disability; no cardiac involvement recessive
LGMD2B mutations in dysferlin gene, causing deficiency of dysferlin protein; protein normally plays a role in muscle-fiber membrane repair average onset 19-27 years; starts with upper leg weakness; weakness becomes more generalized, including lower leg muscles, arm muscles; most walk into 30s; cramps and muscle discomfort in some; no cardiomyopathy recessive
LGMD2C mutations in gamma-sarcoglycan gene, causing deficiency of gamma-sarcoglycan protein; protein normally in muscle-fiber membrane average onset 5-6 years; proximal greater than distal weakness; lordosis ("swayback"); loss of walking at age 16 on average; respiratory muscle failure in 20s; hearing loss can occur; normal intelligence; heart usually normal, but occasionally becomes involved late in disease course recessive
LGMD2D mutations in alpha-sarcoglycan gene, causing deficiency of alpha-sarcoglycan protein; protein normally in muscle-fiber membrane onset ages 2-15; proximal more than distal weakness; with later onset, walking may be preserved; cardiomyopathy is rare recessive
LGMD2E mutations in beta-sarcoglycan gene, causing deficiency of beta-sarcoglycan protein; protein normally in muscle-fiber membrane onset before age 3 to teens; proximal muscle weakness; wheelchair often required around age 10-15 and usually by age 25; cardiomyopathy occurs occasionally recessive
LGMD2F mutations in delta-sarcoglycan gene, causing deficiency of delta-sarcoglycan protein; protein normally in muscle-fiber membrane onset 2 to 10 years; proximal weakness; cramps; wheelchair required ages 9 to 16 in most; normal intelligence; heart often normal but cardiomyopathy may occur recessive
LGMD2G mutations in telethonin gene, causing deficiency of telethonin protein; protein normally plays a role in sarcomere onset 9 to 15 years; weakness in upper arm and leg muscles, lower leg muscles; about 40 percent experience loss of walking ability by 20s or 30s; cardiac involvement in 55 percent recessive
LGMD2H, also known as Mannitoba (Canada) Hutterite dystrophy mutations in TRIM32 gene, causing deficiency of TRIM32 protein; protein normally labels other proteins for destruction onset ages 8 to 27; mild proximal weakness, with back pain and fatigue; slow progression; often walking after age 50 recessive
LGMD2I mutations in fukutin-related protein (FKRP) gene, causing deficiency of FKRP protein; protein normally plays a role in sugar-coating a protein called alpha-dystroglycan common in Denmark and England; onset 6 months to 27 years; weakness of leg and arm muscles; respiratory failure in 30 percent; variable severity; pain with exertion can occur; cramps can occur; excretion of muscle protein myoglobin in urine with physical activity in 25 percent (can damage kidneys); ankle contractures; spinal curvature; cardiomyopathy in 30 to 80 percent but usually mild; normal intelligence recessive
LGMD2J mutations in titin gene, causing deficiency of titin protein; protein normally plays a role in sarcomere Onset usually in childhood; weakness more in proximal than distal muscles; usually lose walking ability by age 30, although some still walking at 60; no cardiomyopathy recessive
LGMD2K mutations in POMT1 gene, causing deficiency of POMT1 protein; protein normally plays a role in sugar-coating a protein called alpha-dystroglycan has been seen in Turkish families; onset within first 10 years, with fatigue and difficulty climbing stairs and running, although early motor milestones normal; proximal weakness that is slowly progressive; ankle contractures in 50 percent; intellectual disability recessive
LGMD2L mutations in anoctamin 5 gene, leading to deficiency of anoctamin 5 protein; protein thought to play a role in muscle-fiber membrane repair onset ranges from 11 to 51 years, with weakness of thigh muscles; progresses to weakness of legs and arms, with arms weaker than legs; weakness of pelvic area; slow progression; muscle pain in most; fatigue; walking ability retained; respiratory muscles normal; cardiac muscle normal recessive
LGMD2M mutations in fukutin gene, leading to deficiency of fukutin protein; protein normally plays a role in sugar-coating a protein called alpha-dystroglycan onset before age 6 months, with low muscle tone and delayed motor development; develops into generalized weakness of variable severity; legs weaker than arms although many retain walking ability; normal intelligence or cognitive impairment; spinal rigidity; contractures; some have cardiomyopathy recessive
LGMD2N Mutations in POMT2 gene, causing deficiency of POMT2 protein; protein normally plays a role in sugar-coating a protein called alpha-dystroglycan one girl identified; mild proximal weakness; able to walk; slow running; mild “swayback” spinal curvature; normal intellect; normal eyes recessive
LGMD2O mutations in POMGnT1 gene, causing deficiency of POMGnT1 protein; protein normally plays a role in sugar-coating a protein called alpha-dystroglycan identified in one Irish child; onset at age 12; proximal muscle weakness; contractures of ankles; normal intellect; normal cardiac function; loss of walking ability before age 20 recessive
LGMD2P mutations in dystroglycan gene, causing deficiency of alpha-dystroglycan protein; protein normally plays a role in the matrix surrounding muscle fibers seen in Turkish and British families; onset during first 10 years, with weakness and difficulty with stairs and running; develop proximal more than distal weakness; ankle contractures in 50 percent; mild to severe intellectual disability recessive
LGMD2Q mutations in plectin gene, causing deficiency of plectin 1f protein; protein thought to play a role in linkage of muscle-fiber membrane to sarcomere seen in Turkish families; onset in early childhood, with delayed walking; develop weakness that is more proximal than distal; stable course in childhood with progression in teens and loss of walking ability in adulthood; contractures late in disease course recessive
Your rating: None Average: 3.9 (7 votes)
MDA cannot respond to questions asked in the comments field. For help with questions, contact your local MDA office or clinic or email publications@mdausa.org. See comment policy