Ferencz C
J Med. 1985;16(5-6):497-508.
The previously reported hypothesis of an etiologic association of heart and blood abnormalities was further investigated in a population based study of congenital cardiovascular malformations (CCVM). Three presumed genetic risk factors (CCVM in parents and siblings, heritable blood disorders and maternal mitral valve prolapse) were found to occur significantly more often in cases than in normal controls, irrespective of the presence in the proband of chromosomal or Mendelian lesions. This suggests a specific etiologic origin of the CCVM; the excess of maternal risk components raises the possibility of X-linked inheritance. Observed constellations of heart, blood, and connective tissue disorders within members of a nuclear family may indicate variability of phenotypic expression of a similar biosynthetic defect. A schematic model of abnormal cardiogenesis is presented which supports the above observations with the results of biochemical studies on endothelium, platelets and collagen disorders. It is suggested that teratogenesis results from subtle interactions of genetic sequelae with extrinsic metabolic and xenobiotic effects. This conclusion harmonizes with those derived from experimental animal studies.
在一项基于人群的先天性心血管畸形（CCVM）研究中，对先前报道的心脏和血液异常病因关联假说进行了进一步研究。发现三种假定的遗传风险因素（父母和兄弟姐妹中的CCVM、遗传性血液疾病和母亲二尖瓣脱垂）在病例组中出现的频率显著高于正常对照组，无论先证者是否存在染色体或孟德尔病变。这表明CCVM有特定的病因起源；母亲风险因素的过量增加了X连锁遗传的可能性。在一个核心家庭成员中观察到的心脏、血液和结缔组织疾病组合可能表明类似生物合成缺陷的表型表达存在变异性。提出了一个异常心脏发生的示意图模型，该模型用关于内皮、血小板和胶原疾病的生化研究结果支持上述观察。提示致畸作用是由遗传后遗症与外在代谢和外源性物质效应的微妙相互作用引起的。这一结论与从实验动物研究得出的结论一致。
