Familial effects on the clinical course of multiple sclerosis
Familial effects on the clinical course of multiple sclerosis
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DOI：
10.1212/01.wnl.0000252822.53506.46
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发表时间：
2007-01-30
期刊：
影响因子：
9.9
通讯作者：
Compston, D. A. S.
中科院分区：
文献类型：
--
作者：
Hensiek, A. E.;Seaman, S. R.;Compston, D. A. S.
背景：家族因素影响多发性硬化症 (MS) 的易感性，但尚不清楚是否对该疾病的自然史有其他影响。方法：我们评估了 1,083 个有≥ 2 名一级亲属患有 MS 的家庭，了解发病年龄、临床病程和疾病严重程度的一致性，并调查了这些临床特征在受影响的亲子对中的传播模式。结果：当单独评估时，所有家庭（相关系数 0.14；p < 0.001）、受影响的兄弟姐妹（相关系数 0.15；p < 0.001）和受影响的亲子对（相关系数 0.12；p = 0.03）的发病年龄均一致。受影响的兄弟姐妹之间存在发病年份的一致性（相关系数 0.18；p < 0.001），但亲子组则不然（相关系数 0.08；p = 0.15）。兄弟姐妹之间的临床病程相似（kappa 0.12；p < 0.001），但受影响的父母及其子女则不然（kappa -0.04；p = 0.09）。这种对自然史的影响存在于复发缓解型、原发性和继发性进展型多发性硬化症的所有临床亚组中，反映了对该疾病的发作期和进展期的家族效应。在任何考虑的家庭组内，疾病严重程度都没有一致性（相关系数：所有家庭一起分析，0.02，p = 0.53；受影响的兄弟姐妹组，0.02，p = 0.61；受影响的亲子组，0.02，p = 0.69）。此外，在受影响的亲子对中，没有任何所研究的临床特征的明显传播模式，也没有证据表明基因负荷的预期或影响。结论：家族因素不会显着影响最终疾病的严重程度。然而，它们增加了进行性临床病程的可能性，无论是从发病时还是在疾病复发缓解期之后。家族效应更可能反映遗传而非环境条件。结果与咨询患者相关，并对旨在确定影响疾病自然史的因素的研究设计具有影响。
Background: Familial factors influence susceptibility to multiple sclerosis (MS) but it is unknown whether there are additional effects on the natural history of the disease. Method: We evaluated 1,083 families with >= 2 first-degree relatives with MS for concordance of age at onset, clinical course, and disease severity and investigated transmission patterns of these clinical features in affected parent- child pairs. Results: There is concordance for age at onset for all families (correlation coefficient 0.14; p < 0.001), as well as for affected siblings (correlation coefficient 0.15; p < 0.001), and affected parent- child pairs (correlation coefficient 0.12; p = 0.03) when each is evaluated separately. Concordance for year of onset is present among affected siblings ( correlation coefficient 0.18; p < 0.001) but not the parent- child group (correlation coefficient 0.08; p = 0.15). The clinical course is similar between siblings (kappa 0.12; p < 0.001) but not affected parents and their children ( kappa -0.04; p = 0.09). This influence on the natural history is present in all clinical subgroups of relapsing-remitting, and primary and secondary progressive MS, reflecting a familial effect on episodic and progressive phases of the disease. There is no concordance for disease severity within any of the considered family groups ( correlation coefficients: all families analyzed together, 0.02, p = 0.53; affected sibling group, 0.02, p = 0.61; affected parent- child group, 0.02, p = 0.69). Furthermore, there are no apparent transmission patterns of any of the investigated clinical features in affected parent - child pairs and no evidence for anticipation or effects of genetic loading. Conclusion: Familial factors do not significantly affect eventual disease severity. However, they increase the probability of a progressive clinical course, either from onset or after a phase of relapsing remitting disease. The familial effect is more likely to reflect genetic than environmental conditions. The results are relevant for counseling patients and have implications for the design of studies seeking to identify factors that influence the natural history of the disease.