A genetic study of facial clefting in Northern England

Abstract

A family is reported of 500 facial cleft index cases, attendees for plastic surgery review at hospitals in northern England. Cases displaying malformation syndromes (29 cases, 5.8% of series) were excluded from analysis, after which CL +/- P and CP pedigree data were examined for evidence of polygenic inheritance. The frequencies of affected among parents, aunts and uncles, and first cousins of 324 CL +/- P index cases are respectively 21, 6 and 4 times the population incidence. The sex ratio among index cases increases with severity of defect. Both of these findings are in good agreement with the polygenic mode of inheritance favored for this condition. The frequencies of affected among parents, aunts and uncles, and first cousins of 147 CP index cases are respectively 30, 5, and 9 times the population incidence. Since syndrome-associated clefts have been excluded from analysis, this elevated incidence in first cousins favors the suggestion that multiple genetic forms of CP may exist.