Cognitive impairment and (CTG)n expansion in myotonic dystrophy patients

Background: Myotonic dystrophy (DM) is a genetic multisystemic disease with muscular, endocrine, ocular cardiac and cognitive impairment. The molecula r basis of the disease has been identified in an unstable base triplet (CTG )n repeat located in the 3' untranslated region of the miotonin protein-kin ase (MT-PK) gene on the long arm of chromosome 19, Cognitive impairment cou ld be a direct expression of this genetic alteration at the central nervous system (CNS) level rather than a consequence of the neuromuscular impairme nt. To explore this hypothesis, we tested a group of genetically diagnosed, adult onset DM, of their nonaffected relatives (NAR), of patients with spi nal muscle atrophy (SMA), and of normal controls using the Wechsler Adult I ntelligence Scale (WAIS). Methods: Seventeen adult-onset DM patients, 9 NAR, 10 SMA patients and 20 u nrelated normal controls (NC) were studied, Clinical, neuromuscular and neu ropsychiatric evaluation, which included WAIS and the Schedule for Affectiv e Disorders and Schizophrenia (SADS), were performed on the four groups, DM , NAR and NC were also assessed by a neurophysiological (P-300) evaluation. A DNA analysis was performed in DM and in NAR to measure presence and magn itude of CTG expansion. Results: We found a statistically significant difference between verbal (p < .0003), nonverbal (p < .0001) and total (p < .0001) IQ of DM patients com pared to les of NAR, SMA and NC. Seven out of II WAIS subtests were signifi cantly and consistently lower in DM patients compared to SMA and/or NC. In DM patients there was a statistically significant negative correlation betw een non-verbal (r = -.68; p < .002) and total (r = .59; p < .01) IQ and (CT G)n. Patients with DM had a significantly lower P300 amplitude compared to NAR and NC. Conclusions: Our study indicates that in DM there is a mild but significant cognitive impairment which correlates with the degree of CTG expansion and it is not dependent on the neuromuscular impairment; however further studi es with larger groups of patients and controls are suggested to confirm our results, due To the small sample size and to a possible effect of educatio nal level in our patients. Biol Psychiatry 1999;46:425-431 (C) 1999 Society of Biological Psychiatry.