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Low frequency of androgen receptor gene mutations in 46 XY DSD, and fetal growth restriction
  1. Ngee Lek1,2,
  2. Harriet Miles1,3,
  3. Trevor Bunch1,
  4. Vickie Pilfold-Wilkie1,
  5. Rieko Tadokoro-Cuccaro1,
  6. John Davies1,
  7. Ken K Ong1,4,
  8. Ieuan A Hughes1
  1. 1Department of Paediatrics, University of Cambridge, Cambridge, UK
  2. 2Department of Paediatrics, KK Women's and Children's Hospital, Singapore
  3. 3Royal Hospital for Sick Children, Edinburgh, UK
  4. 4MRC Epidemiology Unit, Institute of Metabolic Science, Cambridge, UK
  1. Correspondence to Dr Ngee Lek, Department of Paediatrics, KK Women's and Children's Hospital, 100 Bukit Timah Road, Singapore; lekngee.sg{at}gmail.com

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.

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