Craniofrontonasal dysplasia: phenotypic expression in females and males and genetic considerations

The phenotype and pattern of inheritance of craniofrontonasal dysplasia were analyzed in 66 affected persons from 18 families, including one four-generation kindred personally studied. Females were more severely affected than males. Affected females had hypertelorism, broad nasal root, frontal bossing, craniosynostosis, syndactyly of toes and fingers, and vertical grooving of nails. Males had increased bony interorbital distances and distances between the inner canthi of the eyes, broad nasal root, broad halluces, and vertical grooving of nails but no craniosynostosis. Affected men transmitted the condition to all of their daughters but to no sons, while affected women transmitted the disorder to about half their daughters and half their sons. This pattern is compatible with X-linked dominant inheritance, but the far milder manifestation of the syndrome in males cannot be explained by simple mendelian genetics.