Objective: To describe mental retardation and microcephaly as initial clinical signs in myotonic dystrophy (MD) with high trinucleotide repeats.
Patients and methods: Two patients with maternally inherited MD were examined. Southern blot analysis was performed and trinucleotide repeat expansions were related to the findings of clinical and magnetic resonance imaging investigations.
Results: Both patients had the large CTG trinucleotide repeat expansions often seen in congenital MD, but they lacked the typical clinical signs. Mental retardation and microcephaly were the leading features present in infancy. Muscular weakness, in contrast, developed after age 35 years. Although there was no evidence for perinatal asphyxia or sleep apnea, magnetic resonance imaging disclosed reduced brain volume and subcortical demyelination.
Conclusions: Mental retardation preceding the development of muscle weakness suggests that the cerebral involvement in MD is a direct consequence of the genetic disorder and not mediated by muscle disease. Careful clinical examination of the parents for signs of MD should be considered in patients with cognitive deficits even without apparent muscular involvement.