Huntington disease (HD) has been mainly reported in the West and, to date, knowledge on HD in China is very sparse. It has been claimed, that the incidence is very low, however, well-conducted epidemiological studies are lacking. Furthermore, the phenotype in HD patients has not been well characterized, and it may well be that it is influenced by ethnic background. We have therefore performed an analysis of the literature on HD China by systematically retrieving appropriate reports to describe the clinical manifestations of the disease in this country.

Items including Huntington’s disease, Chinese equivalents of the terms: hereditary chorea, chronic progressive chorea, and hysterical chorea were used as keywords to search articles published in the China National Knowledge Infrastructure. Pre-indexing did not reveal any systematic evaluation, prospective or retrospective cohort study regarding HD in China. Case series and individual reports published between January 1 ^st , 1980 and April 30 ^th , 2011 were included, but reviews and experimental studies on HD excluded. Case reports with non-definite clinical diagnosis or repetitive contents were excluded. Information was extracted about family history, involuntary movements, including the region involved, cognitive disturbances, and psychiatric symptoms. Results of imaging and neurophysiological studies, and of genetic testing were included, where available.

Literature inclusion

A total of 230 articles related to HD were collected; 136 were excluded since they reported identical data and basic studies; 94 studies involving 547 patients were selected (Table 1). Of these, 306 cases ad to be excluded due to incomplete clinical data. In total, 279 patients were included (157 males and 122 females), with an age of onset of 6-70 years. Of these cases, 236 cases (96.8%) included a family history. A total of 89 patients were noted to have come from a precise region, 16 were from the South, and the remainder were from the North (82.0%), including 15 from Henan Province, 14 from Shandong Province, and 8 from Hebei Province.

Table 1. Reports included in the present survey

Most (65%) of the patients had onset in middle age (Table2), with a mean of 35.8 years (± 11.8), mean age at death was 45.6 years (± 13.5, range 13–69), and mean course from onset to death was of 11.6 years (± 5.6, range 3–30). Around 9 % had a juvenile onset. The study included 115 families. Paternal inheritance was more often found than maternal inheritance (Table 2), and age of onset with paternal inheritance was lower than maternal inheritance (34 ± 10 versus 37 ± 10 years, P < 0.05). The age at death (46 ± 15 vs. 50 ± 10 years), and the course of disease (12 ± 6 vs. 12 ± 4 years), were not significantly different. In addition, no difference was found between male and female patients in terms of age of onset, death age (47 ± 14 versus 46 ± 12 years), and course of disease (12 ± 6.0 vs. 10.7 ± 5.0 years). Within the cohort, 55 patients death were reported, of which three were due to suicide.

Table 2. Clinical features of the reported patients

	N of total with available data	%
Inheritance
Paternal	127/194	65.5
Maternal	67/194	34.5
Anticipation	42/59	71.2
Age at onset (yr)
< 20	24/279	8.6
30–55	182/279	65.2
Presentation at onset
Abnormal movements	146/196	52.3
Generalized	94/146	64.4
Head and face	20/146	13.7
Upper limbs	29/146	19.8
Lower limbs	3/146	2.1
Psychiatric disorder	45/196	16.1
Cognitive impairment	5/196	1.8
Course
Abnormal movements	242/243	99.6
Psychiatric disorder	85/243	35.0
Cognitive impairment	165/243	67.9

The most frequent presentation at onset were abnormal movement found in more than half of the patients (Table 2), with a predilection for the face and upper limbs when it was not generalized. In the course of the disorder most patients developed abnormal movements, followed by psychiatric symptoms and cognitive impairment (Table 2). There were some specific features in single patients, for example, one displayed speech impairment, instability of gait and cognitive impairment, with no obvious involuntary movement [1]. Dysarthria and dysphagia was also reported during the course in 26 % of the patients. One single patient had epilepsy at onset.

Laboratory investigations

In a total of 48 patients with electroencephalograms, 34 (70.8%) had abnormal curves, mostly with mild slowing. In a total of 16 patients undergoing cerebrospinal fluid examination, three (18.8%) displayed abnormally increased protein levels. In a total of 89 patients undergoing cranial imaging, 80 (90.0%) presented with abnormalities of varying extent, including 65 (73.0%) with brain atrophy and lateral ventriculomegaly, 2 (2.2%) with selective caudate nucleus atrophy, and 26 (29.2%) with brain atrophy, lateral ventriculomegaly, and caudate nucleus atrophy. IT15 gene detection was reported positive in 38 patients, of which CAG repeats were clearly reported in 33 of the cases. The number of CAG repeats was greater in patients with a younger age of onset (mean of 61 in patients with onset before versus 46 with age of onset after 30).

The prevalence of HD is quite variable, with figures varying between 0.5 (Finland) [2], 1 (Croatia [3]) and 10 (German speaking European countries [4]) per 100 000 in Europe, and with high local prevalence in some communities, like in Venezuela (almost 700 in the Lake Maracaibo region [5]. It is usually thought that the prevalence in Asia is lower, however, fewer data than in the West have been reported so far. In Japan reported estimations ranged between 0.1 [6] and 0.7 [7]. Earlier estimation in Hongkong are within the same range [8], however, no data have been so far reported for mainland China. The present survey of Chinese literature on HD shows that the disease is indeed present in this country, but does not provide precise clues on the prevalence of the disorder. It also suggests a higher prevalence in Northern China, however this may also be a report bias. The number of juvenile cases reported seems higher than in other regions of the world and there is a male predominance in overall prevalence. However, the mean age of onset is otherwise consistent, but the course seems shorter with absence of the gender difference reported earlier [9]. The majority of patients had a positive family history, and only five cases were determined to be sporadic. Moreover, the number of cases due to paternal inheritance was significantly greater than that from maternal inheritance, with a significantly younger age of onset with paternal inheritance, which was in accordance with previously published results. Only one case among the 20 with juvenile onset was reported to have epileptic seizure, which is in contrast to the literature, reporting up to 30% of them. Studies have suggested that the suicide rate of HD patients is significantly greater than healthy individuals, in particular in early or advanced stages [10]. Only three patients were reported to have committed suicide, however, data regarding suicide in China are not available for comparison. In general the other aspects were similar to the reports in other populations. However, only a small number had a molecular confirmed diagnosis, but the trend to earlier age of onset with higher triplet repeat numbers is found here also.

In conclusion, ethnic differences among Chinese with HD as compared to other populations are possible. However, the use of appropriate clinical assessment tools and molecular genetic testing in a larger cohort of patients is urgently needed. For this reason a Chinese Huntington’s disease network is going to be launched.

The authors have declared that no competing interests exist