Epidemiology of Huntington's disease in Finland

Highlights

• Huntington's disease has previously been reported to be very rare in Finland.

• The number of diagnoses and mean age at diagnosis have increased in recent decades.

• The minimum prevalence of 2.12/100,000 is four-fold higher than reported previously.

• Relative scarcity of high-risk HTT haplotypes may partly explain the low prevalence.

Abstract

Object

To estimate the prevalence of Huntington's disease (HD) in Finland.

Methods

Persons diagnosed with HD from 1987 to 2010 were identified in the national registers and hospital records of the identified patients, and death certificates of the deceased subjects were obtained. Results of genetic analyses were obtained from the two national laboratories.

Results

Following the discovery of the Huntingtin gene (HTT), the rate of new diagnoses of HD has increased in Finland. We ascertained 207 patients with HD, 114 of whom were alive on 31 December, 2010 suggesting a minimum estimate of point prevalence of 2.12/100,000. The age at the time of diagnosis was 52.6 ± 12.1 years (mean ± standard deviation) and the duration of the disease was 8.5 ± 4.4 years among deceased patients. The length of the CAG repeats in the affected allele was 43.3 ± 3.5 repeats and the length was inversely correlated with the age at diagnosis (β = −0.73, p < 0.001). The number of diagnoses varied regionally, whereas the repeat length did not. The frequency of the high risk HTT haplogroup A was 39% in Finnish chromosomes abstracted from the 1000 Genomes database compared to 53% in other European samples (p = 0.024).

Conclusions

The annual rate of HD diagnoses and the age at diagnosis have increased. The prevalence of HD in the Finnish population is lower than that of other Caucasian populations, partly explained by the low frequency of HTT haplogroup A among the Finns.

Introduction

Huntington's disease (HD) is a neurodegenerative disorder that is manifested with motor symptoms, such as chorea, and is accompanied by psychiatric and cognitive dysfunction [1]. It is a monogenic disease with autosomal dominant inheritance and is caused by an expanded cytosine-adenine-guanine (CAG) repeat in the HTT gene coding for Huntingtin [2]. The affected trinucleotide repeat exhibits a tendency to expand further, especially when inherited from the father [3]. The disease usually becomes manifest between the ages of 30 and 50 years, but the onset of symptoms can occur at any age [4].

The overall prevalence of HD is 5.6/100,000 among Caucasian populations, however, with wide variation [5]. Recently, prevalence estimates as high as 12.3–13.7/100,000 have been reported [6], [7]. The prevalence seems to be lower in Asian and African populations being, for instance 0.5/100,000 in Japan. Among Europeans, 95% of the affected chromosomes of patients with HD, but only 53% of chromosomes with a CAG repeat length in the normal range (<27), belong to a distinct haplogroup defined by single nucleotide polymorphisms in the HTT region [8]. The frequency of haplogroup A is similar in European and Asian populations, but the haplogroup A variants A1 and A2 conferring high risk of HD are not found in Asian populations, whereas they comprise 31% of haplogroup A in the general population in Europe.

The prevalence of HD in Finland has been reported in 1987 to be 0.5/100,000 [9]. The disease was deemed rare to the extent that this was considered a negative feature of Finnish disease heritage [10], [11], an enrichment of rare monogenic diseases in the Finnish population that has been suggested to result from long-term genetic drift rather than founder effects [12]. The discovery of the HTT gene and the causative mutation in 1993 has improved the diagnostics of HD and here we report the prevalence of this disease in Finland based on comprehensive screening of diagnoses made during the last 25 years.