Abstract
Objectives
Until recently a definite diagnosis of Huntington's disease could 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 confirmation became available.
The
aim of this study was to determine to what extent 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 using traditional criteria.
Patients and Methods
From all 191 referred patients suspected of having Huntington'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 (>35) were finally diagnosed as having Huntington's disease. The family history
was compared with the repeat length and the clinical features.
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Results
Clinical
information was obtained for 172 patients. Of these, 126 patients had an expanded repeat, 77 had a positive, eight a negative,
40 a suspect, 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
Conclusion
Despite verification of the family history through the Leiden
roster, many more patients and families could be diagnosed with the new approach than would have been possible with the traditional
criteria. Because prevalence studies have been based on this type of information, the data suggest an underestimation of the
prevalence of Huntington's disease in the community of 14%.
Source: J Neurol Neurosurg Psychiatry 2000;69:54-59 ( July ) Article (J Neurol Neurosurg Psychiatry 2000;69:54-59) S Sieslinga, M Vegter-van de Vlisb, M Losekootb c, R D M Belfroidc,
J A Maat-Kievitb, H P H Kremerd, R A C Roosaa Department of Neurology, K5Q-112 Leiden University Medical Centre, PO Box 9600,
2300 RC Leiden, The Netherlands, Centre for Clinical Genetics, cDepartment of Human Genetics, Department of Neurology, Radboud
Hospital, Nijmegen, The Netherlands. Correspondence to: Professor R A C Roos R.A.C.Roos@LUMC.NL |
