Which clinical history findings help to differentiate among limb-girdle muscular dystrophy (LGMD) types?

Updated: Aug 15, 2019
  • Author: Monica Saini, MD, MBBS, MRCP(UK); Chief Editor: Nicholas Lorenzo, MD, MHA, CPE  more...
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Answer

Typical clinical features to distinguish the main LGMDs are often most helpful early in the disease.

  • LGMD1A: Dysarthria and swallowing difficulty are common. Distal weakness may be present.

  • LGMD1B: Frequent cardiac complications include cardiomyopathy and arrhythmia and there may be a family history of sudden cardiac death. Respiratory complications and contractures are common.

  • LGMD1C: Patients may present with myalgias, rippling muscles, or asymptomatic elevations of CK levels. Calf hypertrophy and toe walking may be prominent. Weakness is proximal and distal.

  • LGMD2A: Onset often in second decade of life. Patients have prominent atrophy of the periscapular muscles, biceps, gluteus maximus, thigh adductors, and hamstring muscles, with sparing of the hip abductors, sartorius, and gracilis. Presentation may be with toe walking. Contractures are common, in which case the disease needs to be differentiated from LGMD1B, Emery-Dreifuss muscular dystrophy, Bethlem myopathy, and laminin-α2 deficiency. This is a common cause of marked hyperCKemia or asymptomatic hyperCKemia.

  • LGMD2B: Patients may have early weakness and/or atrophy of the gastrocnemius (might be detected only on MRI), inability to walk on toes, waddling gait, atrophic distal biceps, and spared periscapular and deltoid muscles. Childhood onset is rare, with often sudden onset in the late teens or early 20s most common. CK can be markedly elevated. Misdiagnosis as polymyositis is not uncommon.

  • LGMD2C-2F: Patients may have Duchenne- and/or Becker-like weakness but with additional involvement of the periscapular muscles causing scapular winging. Muscle hypertrophy is common, especially of the calf and tongue muscles. Mental development is normal. Cardiomyopathy may be present in some. Respiratory complications are common. CK often markedly elevated. Contractures and scoliosis maybe present.

  • LGMD2G: Patients may have initial anterior tibial weakness causing foot drop or a typical LGMD phenotype.

  • LGMD2H: Patients may have a late onset, slow progression, and facial weakness. No cardiac symptoms are present, but mild ECG changes may be noted. This form is reported almost exclusively in the Hutterite population.

  • LGMD2I: This form has a widely variable spectrum with prominent muscle hypertrophy and cardiomyopathy (Duchenne-like). Respiratory complications are common. Patients may have prominent tongue hypertrophy and severe weakness and wasting of upper arms, neck flexors, and axial muscles; these features can help in distinguishing this disease from Duchenne muscular dystrophy.

  • LGMD2J: This is a severe LGMD described in the Finnish population. Distal muscles are affected as the disease progresses. No facial weakness is noted.

  • LGMD2K: This may present with global delay. Mental retardation and microcephaly may be present.

  • LGMD 2L: Adult onset common. Males more severely affected.  Gastrocnemius atrophy and weakness is common. Asymmetry may be prominent. Gradual progression with myalgias and exercise intolerance. CK often markedly elevated.    
  • LGMD2N: This may preset with global delay.

Specific clinical aspects of LGMD subtypes: [4]

  • Autosomal dominant LGMD: Rare, adolescent to late adult onset (LGMD 1B-1D may have childhood onset), mild weakness, normal to mildly elevated CK (except LGMD1C), rare exercise intolerance or rhabdomyolysis (except LGMD1C) 

  • Autosomal recessive LGMD: Common, childhood to young adult onset, moderate to severe weakness, mild to highly elevated CK, common exercise intolerance or rhabdomyolysis

  • LGMDs with cardiac involvement: α-dystroglycanopathies, sarcoglycanopahies, myofibrillar myopathies, laminopathy (and other nuclear envelope proteins), LGMD1C (caveolinopathy), LGMDs with respiratory involvement: α-dystroglycanopathies, sarcoglycanopathies, myofibrillar myopathies, LGMD2V (acid maltase deficiency)

  • LGMDs with distal weakness (anterior compartment); myofibrillar myopathies

  • LGMDs with distal weakness (posterior compartment); LGMD2B (dysferlinopathy) LGMD2L (anoctaminopathy)

  • LGMDs with calf hypertrophy; α-dystroglycanopathies, sarcoglycanopathies, LGMD1C (caveolinopathy)

  • LGMDs with scapular winging: α-dystroglycanopathies, sarcoglycanopathies, LGMD2A (calpainopathy), myofibrillar myopathies, LGMD2B (dysferlinopathy), LGMD2L (anoctaminopathy), laminopathy (and other nuclear envelope proteins)

  • LGMDs with early/prominent contractures: laminopathy (and other nuclear envelope proteins, LGMD2A (calpainopathy), sarcoglycanopathies 

  • LGMDs with brain involvement: (α-dystroglycanopathies) LGMD2I, LGMD 2K, LGMD 2M, LGMD2N, LGMD 2O, LGMD 2P, LGMD2S, LGMD2T, LGMD2U, LGMD2Z

  • LGMDs with onset in the first decade: LGMD2C-F, LGMD 2H, LGMD2J, LGMD2K, LGMD2M, LGMD2N, LGMD2O

  • LGMDs with onset in second decade: LGMD2A, LGMD2G, LGMD2I, LGMD1B, LGMD1C, LGMD1E, LGMD1F

  • LGMDs with onset in adulthood: LGMD2B, LGMD2L, LGMD1A, LGMD1D

  • LGMDs with eye involvement: α-dystroglycanopathies, HNRPDL

  • LGMD with liver involvement: TRAPPC11

  • KGMD with skin involvement: PLEC1

  • LGMDs with myotonic /discharges on Electromyography ( EMG) : LGMD1A, LGMD1D, LGMD1E


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