Low frequency of androgen receptor gene mutations in 46 XY DSD, and fetal growth restriction. Issue 4 (23rd December 2013)

• Record Type: Journal Article
• Authors: Lek, Ngee; Miles, Harriet; Bunch, Trevor; Pilfold-Wilkie, Vickie; Tadokoro-Cuccaro, Rieko; Davies, John; Ong, Ken K; Hughes, Ieuan A
• Is Part Of: Archives of disease in childhood. Volume 99:Issue 4(2014)
• Page Start: 358
• Page End: 361
• Publication Date: 2013-12-23
• Subjects: Children -- Diseases -- Periodicals; Infants -- Diseases -- Periodicals; 618.920005
• DOI: 10.1136/archdischild-2013-305338
• Languages: English
• ISSNs: 0003-9888

Abstract

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.