Myotonic dystrophy
Incidence
It is the most frequent autosomal muscular dystrophy. It has autosomal dominant inheritance. Its prevalence estimates ranging from 2 to over 100 per 100,000, with an average incidence around 1 in 7000 to 8000 births for most European populations.
Clinical Characteristics
Myotonic dystrophy is the most frequent autosomal muscular dystrophy. The frequency of clinically obvious myotonic dystrophy in different populations varies considerably. It is a multisystem disorder, involving heart, smooth muscle, central nervous system, eye, and endocrine glands as well as skeletal muscle. The autosomal muscular dystrophies are responsible for a considerable proportion of chronic neuromuscular disease, particularly in adult life. Myotonic dystrophy, the most frequent member of the group and the only one so far understood in molecular terms, is the commonest adult muscular dystrophy and in its congenital form is often fatal. Unique among the progressive muscular dystrophies, it is characterized by myotonia, which results from an electrophysiological disturbance whose mechanism is likely to differ from that producing myotonia in other, nonprogressive myotonic disorders. Myotonic dystrophy has autosomal dominant inheritance, is exceptionally variable both within and between families, and shows anticipation, with earlier age at onset and more severe clinical features in successive generations. The most severe cases with congenital onset are maternally inherited. Clinical Features: Myotonic dystrophy is one of the most variable disorders known, and it has presenting features that are often non-neurologic. The condition must be considered in a framework much broader than that of the other muscular dystrophies. Nevertheless, the commonest symptoms are neuromuscular, principally relating to muscle weakness and myotonia (delayed muscular relaxation), the latter being most commonly interpreted as stiffness. It can be seen that the muscles involved contrast strikingly with those involved in the X-linked Duchenne and Becker dystrophies, the only autosomal dystrophy with a somewhat similar pattern of muscle group involvement being facioscapulohumeral dystrophy. The mainly distal limb involvement can cause confusion with neuropathic conditions such as Charcot-Marie-Tooth disease, but the recognition of myotonia allows a specific clinical diagnosis of myotonic dystrophy to be made immediately. Involvement of facial and jaw muscles is almost invariable in myotonic dystrophy; ptosis can be marked, while selective weakness and wasting of sternomastoid muscles is seen in the neck. Presenting symptoms in Myotonic Dystrophy: Muscle weakness 35%, Myotonia 21%, Asymptomatic (family study) 18%, Mental retardation 12%, Cataract 5%, Neonatal problems 3%, Other 5%. Muscles most prominently affected are: superficial facial muscles, levator palpebrae superioris, temporalis, sternocleidomastoids, distal muscles of forearm, dorsiflexors of foot. Other muscles commonly affected are: quadriceps, diaphragm and intercostals, intrinsic muscles of hands and feet, palate and pharyngeal muscles, tongue, external ocular muscles. Muscles frequently spared are: pelvic girdle, hamstrings, soleus and gastrocnemius. Myotonia can most readily be recognized by direct percussion of the muscles (in particular the thenar eminence) or by testing for rapid relaxation (especially of grip or, less commonly, eye closure). While most patients complain of stiffness in relation to their myotonia, this is frequently not mentioned unless directly inquired about. The extramuscular features of myotonic dystrophy are of special importance, both in the diagnosis of relatives at risk and in terms of prognosis and management of the affected individual. Some of these can be related to smooth or cardiac muscle dysfunction, while others involve entirely different systems. Smooth muscle involvement may show itself in a variety of ways, but esophageal dysfunction may result in dysphagia and in bronchial aspiration causing pneumonia, while abdominal pain from colonic involvement may result in unnecessary and hazardous surgery. Among other systemic abnormalities are cataracts, characterized by highly distinctive multicolored subcortical lens opacities when viewed with the slit lamp; a variety of endocrine changes, of which testicular tubular atrophy in males is most prominent; and various degrees of central nervous system involvement, ranging from increased somnolence, apathy, and mild personality deterioration in some adults to severe mental retardation in a proportion of congenitally affected patients. Some patients presenting with these systemic features (notably cataract) may have only minimal or occasionally no detectable muscle abnormality, even on careful investigation. There is currently no specific therapy that will arrest or significantly modify the progressive dystrophic changes that occur in patients with myotonic dystrophy, nor can the cardiac or other systemic abnormalities be specifically treated.
Precipitants
no
Provocation Tests
Myotonia can most readily be recognized by direct percussion of the muscles (in particular the thenar eminence) or by testing for rapid relaxation (especially of grip or, less commonly, eye closure).
Diagnostic Procedures
Diagnostic Tests Used for Myotonic Dystrophy: Electromyography: Myotonic potentials. Electromyography will confirm the presence of the myotonia and is of particular importance in distinguishing other syndromes with muscle stiffness, including various familial cramping disorders (generally electrically silent) and disorders of presynaptic origin (generally showing persistent electrical activity at rest). While the presence of myotonia will not distinguish myotonic dystrophy from other myotonic disorders such as myotonia congenita, the finding of myotonia together with "dystrophic" changes, such as diminished action potential amplitude and the presence of polyphasic potentials, in the context of a progressive neuromuscular disorder, is suggestive of myotonic dystrophy. Slit-lamp examination: Multicolored lens opacities. Muscle biopsy: Internal nuclei, other specific changes. Glucose and insulin tolerance tests: Impaired glucose tolerance; hyperinsulinism. Electrocardiogram: Conduction defects; prolonged PR interval. DNA analysis: Expansion of specific unstable sequence. DNA analysis for the expanded unstable sequence is important as a diagnostic test for the disorder as well as for prediction in a family. The correlation between DNA expansion and severity may also prove helpful as an approximate guide to prognosis, while failure to find the abnormality should lead to reassessment of the diagnosis. No single test apart from that for the mutation can be considered pathognomonic. The specific molecular defect in myotonic dystrophy has now been elucidated. The gene, which is expressed in various tissues, including heart, skeletal muscle, and brain, has been sequenced and codes for an mRNA of around 2400 bases. The mutation causing myotonic dystrophy is the expansion of a CTG repeat near the 3´ end of the gene. This is present in less than 30 copies in normal individuals but in 50 copies or more in minimally affected myotonic dystrophy patients. The identification of this molecular defect now allows the specific diagnosis of myotonic dystrophy in relation to other neuromuscular disorders as well as accurate prenatal diagnosis and presymptomatic testing.