Myotonic dystrophy - Muscular dystrophies

Muscular dystrophies

Myotonic dystrophy

Definition

Inherited disease of adults causing progressive muscle weakness. Myotonia is a continued muscle contraction after the cessation of voluntary contraction.

Incidence

Affects 1 in 8000 of the population.

Age

Onset 20–50 years.

Sex

M = F

Aetiology/pathophysiology

Autosomal dominant condition with variable penetrance. Most patients have an amplified trinucleotide (CTG) repeat sequence in the DM(1) gene on chromosome 19. Myotonic dystrophy demonstrates genetic anticipation. Each generation has increased numbers of repeats resulting in an earlier onset and more severe disease. The gene codes for a protein kinase, which is present in many tissues, the mechanism by which this causes the observed clinical features is unknown.

Clinical features

Patients develop ptosis, weakness and thinning of the face and sternomastoids. They have myotonia, delayed muscle relaxation after contraction, e.g. slow relaxation of grip after shaking hands. Other features include cataracts, frontal baldness in males, mild intellectual impairment, dementia, cardiomyopathy and conduction defects, and weakness of distal limb muscles, which may be severe in late stages. There is an increased risk of diabetes mellitus.

Investigations

EMG shows myopathic potentials and myotonia. The diagnosis can now be confirmed by genetic testing.

Microscopy

Affected muscles show abnormalities of fibre size, with fibre necrosis, abundant internal nuclei and replacement by fibrofatty tissue.

Complications

Patients show neurofibrillary tangles of Alzheimer’s disease in the brain with ageing. Infants born to mothers with myotonic dystrophy may have profound hypotonia, feeding and respiratory difficulties, clubfeet and developmental delay.

Management

Phenytoin or procainamide may help the myotonia. Supportive splints and foot braces help distal limb weakness. Complications such as diabetes mellitus and cardiac failure should be regularly screened for. Patients should be offered genetic counselling as appropriate.

Prognosis

The condition is gradually progressive with a variable prognosis.