Family history and DNA analysis in patients with suspected Huntington's disease

Objectives-Until recently a definite diagnosis of Huntington's disease coul d be made by a combination of clinical findings, a positive family history, and pathological confirmation. Prevalence data are based on these criteria . After finding the gene and its pathogenic mutation direct diagnostic conf irmation became available. The aim of this study was to determine to what e xtent the direct assessment of CAG repeat length has allowed the diagnoses of additional patients, with atypical psychiatric or neurological disease, or those without a family history, that could otherwise not be diagnosed us ing traditional criteria. Patients and methods-From all 191 referred patients suspected of having Hun tington's disease between July 1993 and January 1996 CAG repeat length was determined and the family history was reviewed in the Leiden roster. After a retrospective search the patients were subdivided in positive, negative, suspect, and unknown family histories. Patients with an expanded repeat (>3 5) were finally diagnosed as having Huntington's disease. The family histor y was compared with the repeat length and the clinical features. Results-Clinical information was obtained for 172 patients. Of these, 126 p atients had an expanded repeat, 77 had a positive, eight a negative, 40 a s uspect, and one an unknown family history. Of the 44 patients with a normal repeat length four had a positive family history. Of the two patients with an intermediate repeat (between 30-36 repeats), one with a negative family history received a clinical diagnosis of Gilles de la Tourette's syndrome. The other had an unknown family history. Conclusion-Despite verification of the family history through the Leiden ro ster, many more patients and families could be diagnosed with the new appro ach than would have been possible with the traditional criteria. Because pr evalence studies have been based on this type of information, the data sugg est an underestimation of the prevalence of Huntington's disease in the com munity of 14%.