Problems arising in correlating clinical and molecular data in myotonic dystrophy

The number of copies of CTG trinucleotide repeats in the myotonic dystrophy gene correlates to a certain degree with the clinical symptoms in the patient. Routine molecular analysis of myotonic dystrophy is performed on peripheral blood cells, detecting the size of the expansion in leukocytes. However, in some cases somatic mosaicism is responsible for the presence of differently sized myotonic dystrophy alleles in different tissues of the same affected individual, complicating diagnosis and prognosis. Here we report two cases in which the correlation between molecular and clinical analysis performed with standard procedures posed some interpretative problems. The first individual was affected by an atypical clinical picture of myotonic dystrophy, the severity of which was not correlated with the low number of triplet repeats detected in his leukocyte DNA. The second case illustrates a prognostic problem in the presence of a low degree expansion in leukocytes. These examples outline the limits of standard molecular and clinical analysis in myotonic dystrophy.