Myotonic Dystrophy and Other Myotonic Disorders

Both DM1 and DM2 are characterized by skeletal muscle weakness and myotonia with additional multisystem involvement. DM1 commonly presents in adolescence and early adult life, as well as a severe congenital form. DM2 typically begins in adulthood. In contrast to DM1, there is no congenital form of DM2. These two genetically determined myotonic disorders occur in relation to expanded repeats in the noncoding regions of DMPK (DM1) and ZNF9 (DM2) genes.

The onset of DM1 is insidious; patients initially notice distal weakness of the feet and hands, along with myotonia, described by patients as muscle “stiffness,” manifested by difficulty in relaxing muscles after strong contractions. Weakness slowly progresses, ultimately involving most muscle groups in a symmetric fashion. The phenotypic appearance of a long face with hanging jaw and hollowing of the temples develops as a result of wasting and weakness of the facial and neck muscles, as well as early-onset cataracts, is very characteristic of DM1. In contrast to many disorders of muscle, having a stereotyped proximal distribution, DM1 weakness typically has a pronounced distal predominance. These patients also have an accompanying cranial musculature weakness as characterized by ptosis, dysarthria, nasal-quality voice, and dysphagia. Muscle stretch reflexes are usually reduced or absent. Myotonia is the almost universal clinical finding; it is aggravated by cold exposure. Asking the patient to grip examiner’s fingers elicits a classic slow relaxation of the fingers. In addition, the examiner can also elicit myotonia by striking the thenar eminence with a reflex hammer and observing a brisk abduction contraction of the thumb abductor pollicis brevis, followed by a slow relaxation of same with return of the thumb to neutral posture.

DM2, also known as proximal myotonic myopathy (PROMM), presents with hip-girdle weakness (difficulty arising from a squat, getting out of a chair, and climbing stairs), and in contrast to DM1, facial and distal weakness is uncommon. In DM2, pain and stiffness are major complaints, leading patients to their physician in hopes of finding a form of medical therapy. However, this form of myotonia is usually mild.

DM1 is further characterized by the concomitant presence of very significant systemic disorders; in contrast, these are typically absent or mild in DM2. Cardiac conduction disturbances are seen in one half to two thirds of patients with DM1 and are less common in DM2; atrial fibrillation and flutter are the most common arrhythmias. Cataracts occur in more than 90% of patients with DM1 and DM2; the cataracts are indistinguishable in the two disorders. Changes in cognition and behavior are frequently observed in patients with DM1 but not DM2. Endocrinologic dysfunction is also a prominent issue in DM1 men. They have decreased sperm formation and low testosterone levels; in contrast, menstrual irregularities and infertility occur in women. Early frontal and temporal balding and glucose intolerance and hyperinsulinemia are also common in DM1 and less so in DM2. Respiratory involvement may be seen in DM1, sometimes precipitated by general anesthesia, and excessive daytime somnolence is prevalent. There is an increased risk for malignant hyperthermia in DM1 so that careful planning and precautions must be taken when a general anesthetic is required.

Laboratory findings typically demonstrate no to a slight elevation in serum CK in DM1 and a mild hyper-CKemia in DM2. The characteristic electromyography (EMG) finding in both DM1 and DM2 is electrical myotonia, typically consisting of repetitive discharges of muscle fiber action potentials at 20 to 80 Hz, which wax and wane in amplitude and frequency, producing a sound often reminiscent of a dive bomber or a motorcycle engine. Muscle biopsy in DM1 and DM2 is notable for a marked increase of internalized nuclei (arrayed in chains in longitudinal section) and severely atrophic muscle fibers with pyknotic nuclear clumps. Deoxyribonucleic acid (DNA) testing may be particularly useful in DM2, especially when EMG myotonia is not very prominent.

Congenital DM1 is characterized by profound hypotonia, facial diplegia, poor feeding, arthrogryposis (especially of the legs), and respiratory failure. Affected infants have a characteristic “V” shape of the upper lip that results from facial diplegia. With intensive support, most infants survive the neonatal period. In early childhood, there is often a gradual improvement of motor function, but some degree of hypotonia and facial weakness persists; at age 3 to 5 years, foot deformities, learning, and behavioral abnormalities present as the main clinical problems. Mental retardation is a predominant feature of the congenital and childhood forms of DM1. As patients with congenital DM1 age, they develop many of the symptoms and signs of classic, adult-onset DM1.

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