Background: Knowledge about HD in China is lacking in the international literature. We have therefore analyzed the Chinese literature to thoroughly explore the clinical characteristics of Huntington disease in China.
Methods: A computer-based online search of China National Knowledge Infrastructure was performed to review case reports concerning HD published between January 1980 and April of 2011, and the clinical characteristics were extracted.
Results: A total of 92 studies involving 279 patients (157 males and 122 females) were collected, 82.0% of which were from provinces of North China. Most of the cases (97.8%) had a family history of HD, and paternal inheritance (65.5%) was higher than maternal inheritance (34.5%). Onset age was 35.8 (± 11.8) years, death occurred with 45.6 (± 13.5) years after a course of 11.6 (± 5.6) years. Involuntary movements were the most frequent reported presentation (found in 52.3%, including 64.4% in the entire body, 19.8% in the upper limbs, and 13.7% in the head and face). Psychiatric symptoms at onset were reported in 16.1%, and cognitive impairment in 1.8%. With disease progression, 99.6% of patients had abnormal movements, 67.9% cognitive impairment, and 35.0% suffered psychiatric symptoms. Of the reported patients, only 22 underwent IT15 gene testing with positive results.
Conclusion: HD is a well-reported entity in Chinese medical literature, however, only a small number of instances have been proven by molecular diagnosis. Most of the features resemble what is known in other countries. The highly predominant motor presentation, and the higher male prevalence as well as the apparent concentration in Northern China may be due to observational bias. There is therefore a need to prospectively examine cohorts of patients with appropriate comprehensive assessment tools including genetic testing.
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.
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
|Year of publication||First author||Male||Female||Molecular testing||Ref.|
|N||Age at onset||N||Age at onset|
|1980||Wenshi Li||2||37 to 42||1||54||na|||
|1983||Qian Xu||5||15 to 44||3||7 to 8||na|||
|1984||Zian Chen||4||32 to 39||1||32||na|||
|1985||Xiaolian Du||2||5 to 40||3||16 to 19||na|||
|1985||Shuyou Fang||4||28 to 46||1||24||na|||
|1986||Guiqing Wang||2||28 to 58||1||28 to 58||na|||
|1988||Shuqiang Bu||0||na||2||34 to 37||na|||
|1988||Keqing Ding||3||41 to 55||1||45||na|||
|1989||Yongqian Xing||5||20 to 35||3||25 to 43||na|||
|1990||Yuxiang Xu||4||17 to 42||1||35||na|||
|1990||Chuandong Wu||2||17 to 36||0||na||na|||
|1990||Jiaxi Huang||0||na||4||34 to 40||na|||
|1992||Ke Fan||4||27 to 38||2||38 to 56||na|||
|1992||Changdao Sun||3||24 to 30||2||21 to 25||na|||
|1992||Chengyu Chen||4||27 to 47||0||na||na|||
|1995||Xiaomei Yao||0||na||2||46 to 47||na|||
|1995||Chenghao Chu||4||10 to 65||1||20||na|||
|1997||Jiaming Xia||3||18 to 35||2||18||na|||
|1998||Xiangming Fang||5||18 to 40||0||na||na|||
|1998||Yujin Zhang||6||24 to 50||4||30 to 55||na|||
|1998||Xiaoping Yang||2||30 to 40||2||13 to 33||na|||
|1998||Zuozhi Gao||2||33 to 54||1||34||na|||
|1998||Xiaoping Zeng||3||43 to 54||1||45||na|||
|1998||Yuchen Sun||1||42||2||45 to 46||na|||
|1999||Bin Liu||4||32 to 45||3||34 to 38||na|||
|2001||Wen Li||2||21 to 26||3||25 to 26||na|||
|2001||Qinglin Dong||4||23 to 36||2||30 to 32||na|||
|2001||Liansheng Xu||5||29 to 54||5||32 5o 52||na|||
|2002||Jing Liu||3||28 to 46||5||35 to 50||na|||
|2003||Huize Ma||2||31 to 52||3||33 to 45||na|||
|2003||Yuhai Zhao||2||22 to 40||1||30||N CAG repeats|||
|2004||Feng Tian||1||54||2||38 to 50||na|||
|2004||Jun Chen||2||52||2||44 to 54||na|||
|2004||Jiamu Wu||2||31 to 33||0||na||na|||
|2004||Beilei Zhu||1||28||0||na||Genetic test (no N CAG repeats)|||
|2006||Huamei Wang||2||41 to 48||0||na||na|||
|2006||Fang Lin||4||421 to 58||0||na||na|||
|2006||Baorong Zhang||3||30 to 45||5||18 to 36||N CAG repeat|||
|2006||Zhilin Shi||2||33 to 45||1||45||Genetic test (no N CAG repeats)|||
|2007||Yuan Liu||3||33||1||17||N CAG repeats|||
|2007||Yanchun Geng||2||28 to 29||0||na||na|||
|2008||Wei Xu||3||25 to 36||2||27 to 45||Genetic test (no N CAG repeats)|||
|2008||Jin Yu||1||41||4||32 to 45||na|||
|2008||Ning Wang||1||na||2||na||N CAG repeat|||
|2008||Zhouri Li||2||40 to 43||1||41||na|||
|2009||Xingwang Song||2||41 to 57||4||6 to 58||N CAG repeat|||
|2009||Qiuhong Zheng||2||50 to 60||3||41 to 60||na|||
|2009||Meiying Cai||1||30||2||35 to 45||N CAG repeat|||
|2010||Ge Gao||3||36 to 42||0||na||N CAG repeat|||
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
Age at onset (yr)
Presentation at onset
Head and face
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 . Dysarthria and dysphagia was also reported during the course in 26 % of the patients. One single patient had epilepsy at onset.
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) , 1 (Croatia ) and 10 (German speaking European countries ) per 100 000 in Europe, and with high local prevalence in some communities, like in Venezuela (almost 700 in the Lake Maracaibo region . 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  and 0.7 . Earlier estimation in Hongkong are within the same range , 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 . 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 . 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
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