Arch Hellen Med, 31(4), July-August 2014, 433-445
A study of hereditary ataxias in the Greek population
G. Koutsis,1 A. Kladi,1 G. Karadima,1 H. Houlden,2 N.W. Wood,2 C. Christodoulou,3 M. Panas1
OBJECTIVE To study hereditary ataxias in the Greek population, focusing on the prevalence, geographical distribution and phenotypic and genotypic spectrum of Friedreich's ataxia and dominant ataxias, also known as spinocerebellar ataxias (SCA).
METHOD The study included 192 consecutive index patients with suspected hereditary ataxia referred to the Neurogenetics Unit of the Eginition Hospital, Athens over a period of 19 years. For prevalence estimates all non-index patients still alive from the Athens cohort were included, along with a small group of patients with ataxia referred to the Cyprus Institute of Neurology and Genetics for molecular diagnosis.
RESULTS The minimum prevalence of Friedreich's ataxia was estimated at 0.9/100,000. A higher prevalence was noted in the Aegean islands, with clusters of very high prevalence in the islands of Ikaria and Melos. The minimum prevalence for SCA was 0.7/100,000. The genotypic and phenotypic spectrum of Friedreich's ataxia was not significantly different from that documented in other European populations; one patient was found to be a compound heterozygote for a known point mutation in FXN (Asn146Lys). Undiagnosed hereditary ataxias included a majority of Friedreich-like and spastic ataxias. Regarding the different SCA genetic subtypes, SCA1, SCA2, SCA6, SCA7 and SCA17 were identified, SCA1 and SCA7 being the most common dominant ataxias in this cohort, while no patient had SCA3, the most common SCA in many European populations. In total, a molecular diagnosis was reached in 30% of dominant ataxias. Undiagnosed SCA patients included a majority with type III dominant ataxias (pure ataxias).
CONCLUSIONS Friedreich's ataxia is the commonest hereditary ataxia in the Greek population, with prevalence somewhat below the European average, and dominant SCAs are the second in frequency. Patients with SCA1, SCA2, SCA6, SCA7 and SCA17 comprise the spectrum of Greek patients with ataxia with a specific molecular diagnosis, but SCA3 (Machado-Joseph disease) appears to be very rare in the Greek population. Based on the above findings, a diagnostic algorithm is proposed for the molecular approach to hereditary ataxias in Greece.
Key words: Friedreich's ataxia, Greece, Hereditary ataxias, Population study, Spinocerebellar ataxias.