Arch Hellen Med, 28(6), November-December 2011, 785-793
Huntington's disease. A genetic and epidemiological study in the Greek population
Α. Kladi, G. Karadima, E. Vassos, N. Kalfakis, D. Vassilopoulos, M. Panas
OBJECTIVE Huntington's disease (HD) is a progressive autosomal dominant neurodegenerative disorder, characterized by choreic movements, cognitive decline and psychiatric disturbances. The mutation responsible for the disease is an unstable expansion of a trinucleotide CAG repeat in the first exon of the HHT gene, located on chromosome 4q16.3. A large scale prospective genetic and epidemiological study of HD was carried out in Greece between January 1995 and December 2008, the aims of which were to (a) determine the demographic, clinical and epidemiological features of HD in Greece, and (b) evaluate the characteristics, outcome and uptake of the molecular analysis testing for HD performed in Greece from 1995 to 2008.
METHOD Diagnostic testing was carried out in 717 individuals, including 461 symptomatic patients and 256 who were subjected to pre-symptomatic testing. The methodology included clinical evaluation of all the participants, molecular genetic analysis (DNA analysis) for the detection of CAG repeats in the HTT and ATN1 genes and statistical analysis of the results.
RESULTS The diagnosis of HD with a CAG expansion >=36 was confirmed in 278 symptomatic individuals. The prevalence of HD in Greece was estimated at approximately 5.4:100,000 and the mean minimum incidence was estimated at 2.2 to 4.4 per million per year. The molecular diagnosis of HD was confirmed in the majority of patients (84.4%) from whom samples were sent for confirmation. The false-positive cases (15.6%) were characterized by the absence of a family history of HD and the presence of an atypical clinical picture. The uptake of predictive testing for HD was very low (8.6%). Prenatal testing was requested in the case of six pregnancies.
CONCLUSIONS The findings of this study do not differ significantly from those of similar studies in other European countries, despite the relative genetic isolation of the Greek population. Of interest is the identification of high prevalence clusters of HD in Greece.
Key words: Epidemiology, Greece, Huntington's disease, Neurogenetics, Population.