Myotonic Muscular Dystrophy 1 (DM1)
Myotonic muscular dystrophy 1 (DM1) is an autosomal-dominant multisystem muscular dystrophy with an incidence of 1 per 8,000 (7). It represents the most common inherited neuromuscular disease of adults.
The disorder affects skeletal muscle, smooth muscle, myocardium, brain, and ocular structures. Associated findings include baldness and gonadal atrophy (in males), cataracts, and cardiac dysrhythmias. Insulin insensitivity may be present. The gene has been localized to the region of the myotonin protein kinase (DMPK) gene at 19q13.3. Patients demonstrate expansion of an unstable CTG trinucleotide repeat within the region. Molecular genetic testing is available for diagnosis. Normal individuals generally have anesthesia in DM1 due to risk of cardiac arrhythmias and malignant hyperthermia.Twenty-five percent of infants born to myotonic mothers have congenital DM1 and 10% to 15% of all DM1 patients have congenital presentations. CTG repeats in these cases may range from 1,000 to more than 4,000 repeats. Obstetric problems are inversely related to age of presentation of the mother with DM1, and they include polyhydramnios, decreased fetal movements, breech presentation, and preterm labor. Infants show hypotonia, failure to thrive due to an inability to suck, bilateral facial and jaw muscle weakness, craniofacial changes (including a tented upper lip and high-arched palate), neonatal respiratory distress (50%), delayed motor milestones, and delayed speech. Equinovarus deformaties are common. Most children are weaned from the ventilator and walk independently. Clinically, children with congenital DM1 usually show no myotonia over the first five years of life. Those with congenital DM1 usually show significantly reduced IQ, often in the mentally retarded range (77,79). The cognitive impairment is nonprogressive. Behavioral abnormalities include hyperactivity attention-deficit and autistic behavior. Hydrocephalus may be seen in nearly half of patients with congenital DM1. MRI may show hypoplasia of corpus callosum and cerebral white matter changes and diffuse cerebral atrophy. Diagnosis of congenital DM1 is made by molecular genetic studies, as EMG shows no myotonia and CK is usually normal. Muscle biopsy is normal or nonspecific.
In noncongenital DM1, there is evidence for a generally lower intelligence of a mild degree (full-scale IQs have been reported in the 86-92 range) (77). There is a wide range of IQ values found in this population, with many subjects scoring in the above-average range. Cognitive functioning also appears to be related to the size of the CTG expansion at the DM1 gene locus.