Williams D B, Floate D A, Leicester J
Department of Medicine, University of Sydney, N.S.W., Australia.
J Neurol Sci. 1988 Sep;86(2-3):215-30. doi: 10.1016/0022-510x(88)90100-1.
It is likely that adult-onset motor neuron disease is inherited more frequently than has previously been believed. We have studied 9 families with familial motor neuron disease and have found apparently wide variation in penetrance. Only one has autosomal dominant inheritance with high penetrance and in this family the average age of onset is similar to that reported in reviews of familial motor neuron disease. The remaining families have a pattern consistent with autosomal dominant inheritance with diminished penetrance. The average ages of onset in these families are comparable with those in sporadic motor neuron disease. Low penetrance appears to be related to higher average age of disease onset because gene carriers have an increased likelihood of dying from other causes before developing motor neuron disease. When penetrance is low the family history may be unknown, causing affected individuals to be mistakenly regarded as having sporadic disease. We conclude that the incidence of familial motor neuron disease is likely to have been underestimated by the exclusion of apparently sporadic cases in which the familial disease has low penetrance. These results and conclusions imply that the lower average age of disease onset reported in familial motor neuron disease may be due to selective recognition of high penetrance families with lower average ages of onset.
成人起病的运动神经元病的遗传频率可能比以前认为的更高。我们研究了9个家族性运动神经元病家族，发现其外显率存在明显的广泛差异。只有一个家族具有高外显率的常染色体显性遗传，在这个家族中，平均发病年龄与家族性运动神经元病综述中报道的相似。其余家族具有与外显率降低的常染色体显性遗传一致的模式。这些家族的平均发病年龄与散发性运动神经元病的相当。低外显率似乎与较高的疾病平均发病年龄有关，因为基因携带者在患运动神经元病之前死于其他原因的可能性增加。当外显率较低时，家族史可能不为人知，导致受影响的个体被错误地认为患有散发性疾病。我们得出结论，家族性运动神经元病的发病率可能因排除了家族性疾病外显率低的明显散发病例而被低估。这些结果和结论意味着，家族性运动神经元病中报道的较低的疾病平均发病年龄可能是由于选择性地识别了发病年龄较低的高外显率家族。
