Genetics of the Costello syndrome

Am J Med Genet. 1994 Sep 1;52(3):358-9. doi: 10.1002/ajmg.1320520321.


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.

Publication types

  • Review

MeSH terms

  • Abnormalities, Multiple / genetics*
  • Adult
  • Child
  • Developmental Disabilities / genetics
  • Face / abnormalities
  • Female
  • Genes, Dominant
  • Humans
  • Intellectual Disability / genetics
  • Male
  • Maternal Age
  • Nose Neoplasms / genetics
  • Papilloma / genetics
  • Paternal Age
  • Skin Abnormalities
  • Syndrome