Costello Syndrome and Mean Paternal Age of 38 years

Am J Med Genet. 1994 Sep 1;52(3):358-9. Links
Genetics of the Costello syndrome.Lurie IW.
Department of Pediatrics, School of Medicine, University of Maryland, Baltimore.

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.

PMID: 7528974 [PubMed - indexed for MEDLINE]