Limb-girdle Muscular Dystrophy

This term includes at least 15 different variations of inherited disorders.¹ An OMIM search for "limb girdle muscular dystrophy" finds 97 entries.² Initially they affect the muscles around the shoulder girdle and hip girdle. The disease is progressive and may involve other muscles, including cardiac muscle, over a period of time.

The term limb girdle muscular dystrophy was proposed by Walton and Natrass in 1954³ but more recently classification tends to be based on genetic and molecular defects. The earliest descriptions are attributed to Leyden in 1876 and Mobius in 1879.

• It affects both sexes equally.
• It is usually an autosomal recessive (LGMD1)⁴ but a minority are dominant (LGMD2).⁵
• Barth and Macleod syndromes are x-linked and much rarer.
• The overall frequency of all LGMD syndromes is between 5 and 70 per 1,000,000.
• Of the autosomal-recessive syndromes, LGMD 2A (Calpain) is the most common, representing about 30% of cases. LGMD2 may represent a further 20%.
• The sarcoglycanopathies are less common, being about 30% of autosomal-recessive cases. They are classified as LGMD 2C-2F.
• All forms are much rarer than Duchenne muscular dystrophy.

The precise symptoms and signs will vary according to the condition and even within a family there can be significant variation, particularly with regard to rate of progression.

Symptoms

• In most cases the disease starts in late childhood⁶ or early adulthood with weakness of the pelvic girdle muscles so that getting up from a low chair is difficult.
• It progresses to affect the shoulder girdle too.
• Progression over the next 20 to 30 years will lead to considerable weakness and dependence on a wheelchair.
• Age of onset varies from 2 to 40 years and can be different with the same mutation.

Signs

• Muscle weakness in pelvis, hips, upper legs, shoulders
• Loss of muscle mass in those body parts
• Low back pain
• Abnormal, sometimes waddling gait
• Later in the disease, possibly facial muscle weakness
• Later in the disease, muscles of the lower legs, feet, lower arms, and hands can become weak
• Late in the disease, there can be contractures of joints
• Palpitations or syncope from cardiac arrhythmias
• Sometimes the calves will show pseudohypertrophy where they look large but are weak.
• In the sarcoglycanopathies, winging of the scapula is quite common.

• congenital myopathies
• dermatomyositis or polymyositis
• endocrine myopathies including Cushing's syndrome and thyrotoxicosis
• facio-scapulo-humeral muscular dystrophy
• spinal muscular atrophy
• metabolic myopathies including diabetes
• Becker muscular dystrophy
• Duchenne muscular dystrophy.

• Elevated blood creatine kinase levels in almost all types
• EMG shows a pattern of myopathy with fibrillation
• Muscle biopsy for dystrophin, the defective protein in Duchenne muscular dystrophy is negative. Other tests on a muscle biopsy may include light microscopy, electron microscopy and immunochemical staining.
• Muscle biopsy shows degenerating muscle with splitting of muscle fibres and presence of phagocytes. Histochemical stains may be helpful in elucidating the exact form of the disease
• In some less common forms there may be cardiomyopathy showing arrhythmias or heart block⁷ on ECG and heart failure on echocardiogram
• Monitor lung function as it deteriorates with muscular weakness.

By DNA and muscle protein analysis it is possible to identify 5 autosomal dominant and 10 autosomal recessive forms.⁸

Non-Drug

There is no specific treatment but supportive measures can be very helpful. Physiotherapy with passive stretching can prevent contractures. This is particularly important when there is onset in childhood. Aids to daily living will help. Gene therapy may be available in the future.

Drugs

Two small double-blind trials have suggested that co-enzyme Q10 (vitamin Q10) might be beneficial in this and other dystrophies, but larger trials are needed.⁹

Surgical

Surgical treatment may be required for contractures or scoliosis. A pacemaker may help overcome abnormal rhythms.

• Progressive weakness leading to dependence on a wheelchair
• Difficulties with activities of daily living due to shoulder weakness
• Contractures due to decreased muscle movements and joint use
• Scoliosis
• Cardiac arrhythmias.

This depends upon the type. In general slow progression of weakness is to be expected. The affected muscles get worse and it spreads to more muscles. Morbidity and mortality varies between the various types but generally an early onset is associated with a more rapid decline and early mortality. In the slow types the patient may still be ambulatory 30 years later. The autosomal dominat forms tend to be less severe than the recessive.¹⁰

Cardiomyopathy with arrhythmias increases the risk of palpitations, syncope and sudden death. Most patients with this group of diseases live into adulthood but do not reach old age. Death is usually due to cardiac or respiratory failure.

Genetic counselling should be offered if there is a family history