Lurie I W
Department of Pediatrics, School of Medicine, University of Maryland, Baltimore.
Am J Med Genet. 1994 Sep 1;52(3):358-9. doi: 10.1002/ajmg.1320520321.
Although Costello syndrome is considered to be an autosomal recessive disorder, review of 20 families demonstrated that the 37 sibs of the probands were all normal. In 6 families on whom pedigrees were not available, 2 affected sib-pairs were born. Even if there were no normal offspring in these latter families, the occurrence of the Costello syndrome in only 2 of 39 sibs virtually excludes an autosomal recessive inheritance pattern (P = 0.999). Moreover, a significant increase of mean paternal age (38.0 yr) and paternal-maternal age difference (7.36 yr) suggests sporadic autosomal dominant mutations as a likely cause. The 2 reported cases of affected sibs born to healthy parents may be explained by gonadal mosaicism, although heterogeneity with a small proportion of recessively inherited cases cannot be excluded.
尽管科斯特洛综合征被认为是一种常染色体隐性疾病，但对20个家庭的回顾显示，先证者的37个同胞均正常。在6个无法获取家系图谱的家庭中，出生了2对患病同胞。即使后一组家庭中没有正常后代，在39个同胞中仅有2例科斯特洛综合征的发生实际上排除了常染色体隐性遗传模式（P = 0.999）。此外，父亲平均年龄（38.0岁）和父母年龄差（7.36岁）的显著增加表明，散发性常染色体显性突变可能是病因。健康父母生育的2例患病同胞的报道病例可能可以用生殖腺嵌合现象来解释，尽管不能排除存在一小部分隐性遗传病例的遗传异质性。
