Kringlen Gabe, Kinsley Lisa, Aufox Sharon, Rouleau Gerald, Bega Danny
Graduate Program in Genetic Counseling, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Department of Medical Genetics, Sanford Health, Fargo, ND, USA.
J Huntingtons Dis. 2017;6(4):327-335. doi: 10.3233/JHD-170256.
Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder. In most cases the disease is inherited from a parent, although a considerable number of affected persons have no reported family history of the disease. While CAG repeat length is negatively correlated with age of symptom onset, variability exists suggesting that other variables may influence symptom onset.
The objective of this study is to determine whether awareness of a family history of HD has an impact on symptom onset and disease manifestations.
Data were obtained from Enroll-HD to compare subjects with a family history of HD to subjects without on various key clinical outcomes. In addition, multiple regressions were performed to investigate the impact of family history on the age at onset of depression and motor symptoms.
4,285 mutation positive subjects were included in the analysis, of which 4.81% had a negative family history. Controlling for CAG repeat length, a positive family history predicted an onset of depression 11.438 years earlier and an onset of motor symptoms 6.681 years earlier when compared to having a negative family history. Subjects with a positive family history were more likely to report behavioral manifestations as the initial major symptom of HD (38.6% vs. 29.6%, p = 0.023), and were more likely to report previous suicidal ideation/attempts (26.2% vs. 20.3%, p = 0.046).
A positive family history of HD appears to be associated with an earlier onset of depression and overall disease manifestations. Implications regarding the role of genetic versus environmental contributions to symptom onset in HD are discussed.
亨廷顿舞蹈症（HD）是一种常染色体显性神经退行性疾病。在大多数情况下，该疾病是由父母遗传而来，尽管相当一部分患者并无该疾病的家族病史报告。虽然CAG重复序列长度与症状出现的年龄呈负相关，但仍存在变异性，这表明其他变量可能会影响症状的出现。
本研究的目的是确定对HD家族病史的认知是否会对症状出现和疾病表现产生影响。
从亨廷顿舞蹈症注册研究（Enroll-HD）中获取数据，比较有HD家族病史的受试者和无家族病史的受试者在各种关键临床结果方面的情况。此外，进行多元回归分析以研究家族病史对抑郁和运动症状发病年龄的影响。
4285名突变阳性受试者纳入分析，其中4.81%有阴性家族病史。在控制CAG重复序列长度的情况下，与阴性家族病史相比，阳性家族病史预示着抑郁发作提前11.438年，运动症状发作提前6.681年。有阳性家族病史的受试者更有可能报告行为表现为HD的初始主要症状（38.6%对29.6%，p = 0.023），并且更有可能报告既往有自杀观念/企图（26.2%对20.3%，p = 0.046）。
HD的阳性家族病史似乎与抑郁和整体疾病表现的更早发作有关。文中讨论了关于遗传因素与环境因素在HD症状发作中作用的相关问题。
