Carter C O, Evans K, Coffey R, Roberts J A, Buck A, Roberts M F
J Med Genet. 1982 Aug;19(4):246-61. doi: 10.1136/jmg.19.4.246.
A family study of cleft lip, with or without cleft palate, was based on those treated by operation at The Hospital for Sick Children, London, between 1920 and 1939 in order to give information on the proportion affected of children and grandchildren. The probands were those who had survived, were successfully traced, and found to have had at least one child. Care was taken to exclude patients who were traced through a child, whether normal or affected, and not through the usual tracing procedure. Patients with recognised syndromes were also excluded. Because the series was based on patients who had survived and reproduced it was biased in favour of those with milder degrees of the malformation, and against those with any severe associated malformation. The proportion affected of children of probands was 3.15% (+/- 0.56), of sibs 2.79% (+/- 0.52), and of parents 1.18% (+/- 0.37), respectively. The lower proportion of parents affected is attributed to reduced reproductive fitness of patients born two generations ago. The proportion affected of nephews and nieces, aunts and uncles, and grandchildren was 0.47% (+/- 0.18), 0.59% (+/- 0.13), and 0.8% (+/- 0.6) respectively. The proportion affected of first cousins was 0.27% (+/- 0.08). The birth frequency of cleft lip (+/- cleft palate) is estimated to be about 0.1% in England. There were two first cousin and one second cousin marriages among the marriages of the parents. There was no increase of cleft palate among the relatives of the probands. The proportion of sibs affected increased with increasing severity of the malformation in the proband, where the proband was female, and where the proband had an affected parent or already had one affected sib. It was not, however, increased where a more remote relative was affected. The proportion of children affected was not increased when the proband had an affected parent or sib, but few families provided information. The most economical hypothesis to explain the findings is the multifactorial threshold model. The birth frequency of the malformation and the family patterns found make it improbable that one single mutant gene makes a major contribution to the liability to develop the condition.
一项关于唇裂（伴或不伴腭裂）的家系研究，基于1920年至1939年间在伦敦大奥蒙德街儿童医院接受手术治疗的患者，目的是获取有关子代和孙代受影响比例的信息。先证者是那些存活下来、被成功追踪且至少育有一个孩子的人。研究小心地排除了那些通过孩子（无论正常或患病）而非通常追踪程序被追踪到的患者。患有公认综合征的患者也被排除在外。由于该系列基于存活并生育的患者，因此偏向于畸形程度较轻的患者，而不利于有任何严重相关畸形的患者。先证者的子代受影响比例为3.15%（±0.56），同胞为2.79%（±0.52），父母为1.18%（±0.37）。父母受影响比例较低归因于两代前出生的患者生殖适应性降低。侄子侄女、姑姑舅舅和孙代的受影响比例分别为0.47%（±0.18）、0.59%（±0.13）和0.8%（±0.6）。一级表亲的受影响比例为0.27%（±0.08）。在英格兰，唇裂（±腭裂）的出生频率估计约为0.1%。父母的婚姻中有两例一级表亲婚姻和一例二级表亲婚姻。先证者的亲属中腭裂发生率没有增加。同胞受影响比例随着先证者畸形严重程度的增加、先证者为女性、先证者有患病父母或已有一个患病同胞而增加。然而，当更远的亲属患病时，该比例并未增加。当先证者有患病父母或同胞时，子代受影响比例并未增加，但提供信息的家庭很少。解释这些发现的最经济的假说是多因素阈值模型。畸形的出生频率和所发现的家庭模式使得单个突变基因对发病易感性起主要作用的可能性不大。
