title: Genetics of the Costello syndrome.
abstract: 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.
authors.affiliation: Department of Pediatrics, School of Medicine, University of Maryland, Baltimore.
authors.forename: I W
authors.initials: IW
authors.lastname: Lurie
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D000328:Adult; D002648:Child; D002658:Developmental Disabilities / Q000235:genetics; D005145:Face / Q000002:abnormalities; D005260:Female; D005799:Genes, Dominant; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics; D008297:Male; D008423:Maternal Age; D009669:Nose Neoplasms / Q000235:genetics; D010212:Papilloma / Q000235:genetics; D010331:Paternal Age; D012868:Skin Abnormalities; D013577:Syndrome