Limb girdle dystrophy

Published on 02/04/2015 by admin

Filed under Internal Medicine

Last modified 22/04/2025

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65 Limb girdle dystrophy

Instruction

Perform a neurological examination of this patient’s upper and lower limbs.

Salient features

History

• Age of onset (between 10 and 30 years of age)

• Onset may either be in the pelvic or shoulder girdle

• It may remain confined to the pelvic or shoulder girdle and may be static for years before peripheral weakness and wasting occur.

Examination

Upper limbs (Fig. 65.1):

• Biceps and brachioradialis are involved late; wrist extensors are first involved when it extends to the wrist.

• Deltoids may show pseudohypertrophy and are spared until late.

image

Fig. 65.1 Pattern of weakness in limb-girdle dystrophy.

Lower limbs (Fig. 65.1):

• In the early stages of the disease, hip flexors and glutei are weak.

• There is early wasting of medial quadriceps and tibialis anterior.

• Lateral quadriceps and calves may show hypertrophy.

Note: The face is never affected.

Diagnosis

This patient has weakness of the proximal muscles of the arms and legs (lesion) caused by limb girdle dystrophy (aetiology).

Advanced-level questions

What is the mode of inheritance?

Traditionally, it was believed to be autosomal recessive, with males and females equally affected. More recently,the limb girdle muscular dystrophies (LGMDs) have been identified to be inherited either in an autosomal dominant (type 1) or autosomal recessive (type 2) pattern. Six subtypes of the dominant LGMDs (1A to 1F) and 11 subtypes of the recessive LGMDs (2A to 2K) have been reported. In four of the limb girdle dystrophies (2C, 2D, 2E and 2F), mutations affecting the sarcoglycan complex of proteins have been identified. These membrane proteins interact with dystrophin through another transmembrane protein, β-dystroglycan. Dysferlin is a sarcolemmal protein, and its deficiency causes proximal and distal forms of recessively inherited muscular dystrophies, designated as LGMD type 2B.

LGMD2A, the most prevalent form, accounts for at least 30% of all cases and is caused by mutations in CAPN3 (also called p94), which encodes CAPN3, the largely skeletal-muscle-specific member of the calpain superfamily. These patients have symmetrical and selective involvement of proximal limb girdle muscles. They have normal intelligence and no cardiac or facial disturbances. The disease shows wide intrafamilial and interfamilial clinical variability. A dystrophic or myopathic process is seen on muscle biopsy. During the active phase, the serum level of creatine kinase is moderately or markedly increased; however, patients with a normal serum level of creatine kinase or a neurogenic pattern on electromyography have also been reported, suggesting that there is a spectrum of variability in this calpainopathy. Intramuscular administration of the synthetic calpain inhibitor leupeptin to dystrophic Mdx mice can prevent decreases in muscle fibre diameter (Muscle Nerve 2000;23:106–11). Calpain inhibitors, therefore, have the potential of being beneficial in this condition.

What is the age of onset?

Between 10 and 30 years, causing disability 10–20 years after onset.

How is the intelligence affected?

It is unaffected and IQ is normal.

Is the lifespan affected?

No.

What happens to the serum enzymes?

Levels of serum enzymes are slightly affected or normal.

John Walton, Professor of Neurology at Oxford and Newcastle, was made a peer following his retirement and carries the title of Lord Walton of Detchant. His chief interest was muscular diseases.

Sir Roger Bannister, Master of Pembroke College at Oxford, worked at the National Hospital for Nervous Diseases, Queen Square, and St Mary’s Hospital, London, and his main interest was chronic autonomic failure. He was the first person to run the 4-minute mile.

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