title: RASopathies Are Associated With Delayed Puberty; Are They Associated With Precocious Puberty Too?
abstract: RASopathies, such as Noonan, Costello, and cardio-facio-cutaneous syndromes, are developmental disorders caused by mutations in rat sarcoma-mitogen-activated protein kinase pathway genes. Mutations that cause Noonan syndrome have been associated with delayed puberty. Here we report 4 patients with either Costello or cardio-facio-cutaneous syndrome who developed precocious puberty, suggesting complex regulation of the hypothalamic-pituitary-gonadal axis and the timing of puberty by the rat sarcoma-mitogen-activated protein kinase pathway. Additional study of the timing of puberty among patients with RASopathies is warranted to ascertain the incidence of delayed and precocious puberty in these conditions and to examine genotype-phenotype correlations, which may provide insight into pathways that regulate the timing of puberty.
authors.affiliation: Divisions of Endocrinology and d.vanderkaay@hagaziekenhuis.nl.
authors.forename: Daniëlle C M
authors.initials: DC
authors.lastname: van der Kaay
authors.affiliation: Division of Endocrinology, Boston Children's Hospital, Boston, Massachusetts; and.
authors.forename: Bat-Sheva
authors.initials: BS
authors.lastname: Levine
authors.affiliation: Division of Endocrinology, Nemours Alfred I. Dupont Hospital for Children, Wilmington, Delaware.
authors.forename: Daniel
authors.initials: D
authors.lastname: Doyle
authors.affiliation: Divisions of Endocrinology and.|Clinical and Metabolic Genetics, The Hospital for Sick Children, and.
authors.forename: Roberto
authors.initials: R
authors.lastname: Mendoza-Londono
authors.affiliation: Divisions of Endocrinology and.|Departments of Pediatrics and.|Physiology, The University of Toronto, Toronto, Ontario, Canada.
authors.forename: Mark R
authors.initials: MR
authors.lastname: Palmert
mesh_terms: D000015:Abnormalities, Multiple / Q000175:diagnosis / Q000453:epidemiology; D000293:Adolescent; D002648:Child; D056685:Costello Syndrome / Q000150:complications / Q000235:genetics; D004476:Ectodermal Dysplasia / Q000150:complications / Q000235:genetics; D019066:Facies; D005183:Failure to Thrive / Q000150:complications / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology*; D006330:Heart Defects, Congenital / Q000150:complications / Q000235:genetics; D006801:Humans; D015994:Incidence; D008297:Male; D009634:Noonan Syndrome / Q000150:complications / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*; D011628:Puberty, Delayed / Q000209:etiology* / Q000503:physiopathology; D011629:Puberty, Precocious / Q000209:etiology* / Q000503:physiopathology; D018570:Risk Assessment; D012494:Sampling Studies; D012680:Sensitivity and Specificity; D012741:Sexual Maturation / Q000235:genetics* / Q000502:physiology
chemical_list: D016283:Proto-Oncogene Proteins p21(ras)