Limb-girdle muscular dystrophy type 2A

Alternate names

LGMD2A; Calpainopathy; Limb-girdle muscular dystrophy type 2; LGMD2; Muscular dystrophy, pelvofemoral; Leyden-Moebius muscular dystrophy

Definition

Limb-girdle muscular dystrophy type 2A (LGMD2A) is an autosomal recessive limb-girdle muscular dystrophy characterized by progressive, symmetrical weakness of the proximal limb and girdle muscles (mainly those around the hips and shoulders) without heart involvement or intellectual disability.

Epidemiology

Type 2A is the most common form of limb-girdle muscular dystrophy, accounting for about 30 percent of cases.

Cause

The condition is caused by mutations in the CAPN3 gene.

Types

There are three subtypes of autosomal recessive disorders associated with mutations in the CAPN3 gene which differ by the distribution of muscle weakness and age at onset:

• Pelvifemoral limb-girdle muscular dystrophy (also known as Leyden-Mobius LGMD) is the most frequently observed subtype. In these cases, muscle weakness is first evident in the pelvic girdle and later in the shoulder girdle. Onset is usually before age 12 or after age 30;
• Scapulohumeral LGMD (also known as Erb LGMD) usually has milder symptoms with infrequent early onset. In most cases, muscle weakness is first evident in the shoulder girdle and later in the pelvic girdle;
• HyperCKemia is usually observed in children or young individuals. In most cases, those affected do not have symptoms, just high levels of creatine kinase in their blood.

Signs and symptoms

• Clinical findings of calpainopathy include the tendency to walk on tiptoe, difficulty in running, scapular winging, waddling gait, and slight hyperlordosis.
• Other findings include symmetric weakness of proximal more than distal muscles in the limbs, trunk, and periscapular area; laxity of the abdominal muscles; Achilles tendon shortening; scoliosis; and joint contractures.[1].
• Affected individuals typically do not have cardiac involvement or intellectual disability.

Clinical presentation

For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed.

80%-99% of people have these symptoms

• Generalized muscle weakness

30%-79% of people have these symptoms

• Ankle flexion contracture
• Calf muscle hypertrophy(Increased size of calf muscles)
• Congenital finger flexion contractures
• Difficulty walking(Difficulty in walking)
• Elbow flexion contracture(Contractures of elbows)
• Elevated serum creatine kinase(Elevated blood creatine phosphokinase)
• Hamstring contractures
• Hyperlordosis(Prominent swayback)
• Lower limb muscle weakness(Lower extremity weakness)
• Muscular dystrophy
• Pectoralis amyotrophy(Wasting of pec muscles)
• Pelvic girdle amyotrophy
• Proximal muscle weakness(Weakness in muscles of upper arms and upper legs)
• Scapular muscle atrophy
• Scapular winging(Winged shoulder blade)
• Spinal rigidity(Reduced spine movement)
• Toe walking(Toe-walking)

5%-29% of people have these symptoms

• Difficulty climbing stairs(Difficulty walking up stairs)
• Facial palsy(Bell's palsy)
• Wrist flexion contracture

Diagnosis

• The diagnosis of calpainopathy, which is suggested by clinical findings and elevated serum CK concentration, is established by identification of biallelic pathogenic variants in CAPN3 (encoding proteolytic enzyme calpain-3) or a dominantly acting heterozygous pathogenic variant for the CAPN3 21-bp deletion (c.643_663del21) by molecular genetic testing. [2].
• If such testing is not available or not conclusive, muscle biopsy with protein immuno-analysis should be used for diagnostic confirmation.

Treatment

• Physical therapy and stretching exercises to promote mobility and prevent contractures
• Aids such as canes, walkers, orthotics, and wheelchairs to help maintain independence
• surgery for foot deformities, scoliosis, and Achilles tendon contractures as needed
• Respiratory aids to treat chronic respiratory insufficiency in late stages of the disease.[3].

NIH genetic and rare disease info

• NIH info on Limb-girdle muscular dystrophy type 2A

Limb-girdle muscular dystrophy type 2A is a rare disease.

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