title: Ambiguous genitalia: what prenatal genetic testing is practical?
abstract: Concern for ambiguous genitalia or chromosome-phenotype discordance detected in a prenatal setting has increased over the last two decades. Practitioners faced with this prenatal finding have a variety of genetic tests available to them; however, it is unclear to what extent prenatal testing for disorders of sex development (DSD) is useful or practical. We undertook a retrospective review of the medical records of 140 individuals evaluated through the DSD clinic at Seattle Children's Hospital with birthdates from 01/01/1994 through 08/16/2011 to determine the rate of prenatal detection of ambiguous genitalia in individuals with DSD, what prenatal diagnostic workup was undertaken, and the postnatal outcome, including whether a postnatal genetic diagnosis was confirmed. Of all 140 subjects, 34 (24%) were identified prenatally. The most common postnatal diagnoses were penoscrotal hypospadias with transposition of the scrotum with no known genetic cause (24/140; 17%) and 21-hydroxylase deficiency (20/140; 14%). Apart from these, no single diagnosis comprised more than a few cases. Prenatal diagnostic testing varied widely, from no tests to multiple molecular tests with amniotic fluid hormone concentrations. In the absence of other fetal anomalies or growth retardation on ultrasound, prenatal karyotype with fluorescence in situ hybridization for the SRY gene is the most useful test when ambiguous genitalia is suspected. Further prenatal testing for Smith-Lemli-Opitz syndrome in 46,XY individuals and congenital adrenal hyperplasia in 46,XX individuals may be considered. However, targeted molecular testing for rare DSD conditions in the absence of a family history of DSD has a low yield.
authors.affiliation: Department of Pediatrics, University of Washington School of Medicine, Seattle, Washington, USA. margaret.adam@seattlechildrens.org
authors.forename: Margaret P
authors.initials: MP
authors.lastname: Adam
authors.forename: Patricia Y
authors.initials: PY
authors.lastname: Fechner
authors.forename: Linda A
authors.initials: LA
authors.lastname: Ramsdell
authors.forename: Angela
authors.initials: A
authors.lastname: Badaru
authors.forename: Richard E
authors.initials: RE
authors.lastname: Grady
authors.forename: Roberta A
authors.initials: RA
authors.lastname: Pagon
authors.forename: Elizabeth
authors.initials: E
authors.lastname: McCauley
authors.forename: Edith Y
authors.initials: EY
authors.lastname: Cheng
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Parisi
authors.forename: Margarett
authors.initials: M
authors.lastname: Shnorhavorian
mesh_terms: D012734:Disorders of Sex Development / Q000175:diagnosis*; D005260:Female; D005315:Fetal Diseases / Q000175:diagnosis*; D005820:Genetic Testing / Q000379:methods*; D006801:Humans; D008297:Male; D011247:Pregnancy; D011296:Prenatal Diagnosis