title: Perinatal features of the RASopathies: Noonan syndrome, cardiofaciocutaneous syndrome and Costello syndrome.
abstract: The RASopathies are a family of developmental disorders caused by heritable defects of the RAS/MAPK signaling pathway. While the postnatal presentation of this group of disorders is well known, the prenatal and neonatal findings are less widely recognized. We report on the perinatal presentation of 10 patients with Noonan syndrome (NS), nine with Cardiofaciocutaneous syndrome (CFCS) and three with Costello syndrome (CS), in conjunction with the results of a comprehensive literature review. The majority of perinatal findings in NS, CS, and CFCS are shared: polyhydramnios; prematurity; lymphatic dysplasia; macrosomia; relative macrocephaly; respiratory distress; hypotonia, as well as cardiac and renal anomalies. In contrast, fetal arrhythmia and neonatal hypoglycemia are relatively specific to CS. NS, CS, and CFCS should all be considered as a possible diagnosis in pregnancies with a normal karyotype and ultrasound findings of a RASopathy. Recognition of the common perinatal findings of these disorders should facilitate both their prenatal and neonatal diagnosis.
authors.affiliation: Division of Medical Genetics, Department of Pediatrics, Stanford University, Stanford, California.
authors.forename: Angela
authors.initials: A
authors.lastname: Myers
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Bernstein
authors.forename: Marie-Luise
authors.initials: ML
authors.lastname: Brennan
authors.forename: Cynthia
authors.initials: C
authors.lastname: Curry
authors.forename: Edward D
authors.initials: ED
authors.lastname: Esplin
authors.forename: Jamie
authors.initials: J
authors.lastname: Fisher
authors.forename: Margaret
authors.initials: M
authors.lastname: Homeyer
authors.forename: Melanie A
authors.initials: MA
authors.lastname: Manning
authors.forename: Eric A
authors.initials: EA
authors.lastname: Muller
authors.forename: Anna-Kaisa
authors.initials: AK
authors.lastname: Niemi
authors.forename: Laurie H
authors.initials: LH
authors.lastname: Seaver
authors.forename: Susan R
authors.initials: SR
authors.lastname: Hintz
authors.forename: Louanne
authors.initials: L
authors.lastname: Hudgins
mesh_terms: D000015:Abnormalities, Multiple; D056685:Costello Syndrome / Q000175:diagnosis* / Q000235:genetics; D004252:DNA Mutational Analysis; D003937:Diagnosis, Differential; D004476:Ectodermal Dysplasia / Q000175:diagnosis* / Q000235:genetics; D019066:Facies; D005183:Failure to Thrive / Q000175:diagnosis* / Q000235:genetics; D005260:Female; D006330:Heart Defects, Congenital / Q000175:diagnosis* / Q000235:genetics; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D009154:Mutation; D015997:Neonatal Screening; D009634:Noonan Syndrome / Q000175:diagnosis* / Q000235:genetics; D010641:Phenotype; D011296:Prenatal Diagnosis
keywords: Cardiofaciocutaneous syndrome; Costello syndrome; Noonan syndrome; RASopathy; prenatal diagnosis