Genetic heterogeneity for dystrophia myotonica.

The analogy of the haemoglobinopathies sug- gests that at any gene locus there may be numerous different mutations which will have varied clinical effects.Also, there are now a number of examples in medicine of clinically similar conditions which may be caused by mutations at more than one locus.Genetic heterogeneity is likely to be the rule rather than the exception.It is, however, difficult to recognize that there is more than one genetic variant of a condition which, even within families, has such a varied clinical manifestation and age of onset as dystrophia myo- tonica.Nevertheless, in a recent study of 40 index patients and their families (Bundey, Carter, and Soothill, 1970; Renwick et al, 1971) there were indications from intra-familial resemblance in age of onset of the disease that there are at least 2 variants, though both are dominant conditions.The evi- dence is given in this paper. Material and MethodsThe index patients were a consecutive series of 8 patients from The Hospital for Sick Children attending from 1951 to 1968, and 32 patients from The National Hospital for Nervous Diseases between 1947 and 1967.These 40 index patients belong to 36 families.In the single instance of 2 sibs both being index patients at The National Hospital (family 3) it is dubious whether their attendances there were independent events.Accordingly, only the 2nd sib has been counted as an index patient in the calculations of correlations between relatives which are therefore based on 39 index patients.The patients and their first-degree relatives were visited and ex- amined in their own homes.Many of them also attended The National Hospital for special investigation (Bundey et al, 1970).We realize that the age of onset of symptoms may be difficult to determine accurately.Where a patient could date the onset of muscle weakness or myotonia, this has been accepted.Where a patient could only say that symptoms had been present 'for many years' or 'for a long time' without further clarification, his age of onset has been graded as uncertain and has not been