Myotonic dystrophy. The role of large triplet repeat length in the development of mental retardation
M. Spranger, S. Spranger, M. Tischendorf, H. M. Meinck and M. Cremer
Department of Neurology, University of Heidelberg, Germany.
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.
