title: Low frequency of androgen receptor gene mutations in 46 XY DSD, and fetal growth restriction.
abstract: OBJECTIVE
  The diagnosis of partial androgen insensitivity syndrome (PAIS) should be reserved for infants with a pathogenic androgen receptor gene (AR) mutation. However, only about 20% of infants with a clinical phenotype akin to PAIS have an AR mutation. We aimed to identify clinical features associated with the presence of an AR mutation.
  
  
  METHODS
  The external masculinisation score (EMS; normal=12), birth weight (BW), gestational age and BW SD score (BW-SDS) of 164 infants with a 'PAIS-like' phenotype were analysed in the Cambridge Disorders of Sex Development (DSD) Database, of whom 128 (78%) had no AR mutation ('AR mutation-negative') and 36 (22%) had an AR mutation ('AR mutation-positive').
  
  
  RESULTS
  The EMS was similar in AR mutation-negative and AR mutation-positive infants (median, IQR: 5.0, 3.0 to 6.0 vs 4.8, 3.0 to 6.0; p=0.33). AR mutation-negative infants had lower BW (2.33, 1.38 to 3.20 vs 3.18, 2.87 to 3.61 kg; p<0.001), lower gestational age (37.0, 34.0 to 40.0 vs 40.0, 39.0 to 40.0 weeks; p<0.001), and lower BW-SDS (-1.31, -2.33 to -0.46 vs -0.57, -1.19 to 0.33; p=0.001) compared to AR mutation-positive infants. More AR mutation-negative infants (47/128; 37%) than AR mutation-positive infants (2/36; 6%) had BW-SDS <-2 (p<0.001).
  
  
  CONCLUSIONS
  The severity of genital anomalies in this large cohort of infants with a 'PAIS-like' phenotype did not differentiate their AR status. Almost all the infants born small-for-gestational-age do not have an AR mutation. A category of 'XY DSD and fetal growth restriction, as yet unexplained' should be recognised.
authors.affiliation: Department of Paediatrics, University of Cambridge, , Cambridge, UK.
authors.forename: Ngee
authors.initials: N
authors.lastname: Lek
authors.forename: Harriet
authors.initials: H
authors.lastname: Miles
authors.forename: Trevor
authors.initials: T
authors.lastname: Bunch
authors.forename: Vickie
authors.initials: V
authors.lastname: Pilfold-Wilkie
authors.forename: Rieko
authors.initials: R
authors.lastname: Tadokoro-Cuccaro
authors.forename: John
authors.initials: J
authors.lastname: Davies
authors.forename: Ken K
authors.initials: KK
authors.lastname: Ong
authors.forename: Ieuan A
authors.initials: IA
authors.lastname: Hughes
mesh_terms: D013734:Androgen-Insensitivity Syndrome / Q000150:complications / Q000175:diagnosis / Q000235:genetics; D001724:Birth Weight / Q000235:genetics; D016208:Databases, Factual; D058490:Disorder of Sex Development, 46,XY / Q000150:complications / Q000175:diagnosis / Q000235:genetics*; D005317:Fetal Growth Retardation / Q000209:etiology / Q000235:genetics*; D005837:Genitalia, Male / Q000002:abnormalities; D005865:Gestational Age; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D009154:Mutation; D010641:Phenotype; D011944:Receptors, Androgen / Q000235:genetics*; D012720:Severity of Illness Index
chemical_list: D011944:Receptors, Androgen