Low frequency of androgen receptor gene mutations in 46 XY DSD, and fetal growth restriction

• Published in: Archives of disease in childhood Vol. 99; no. 4; pp. 358 - 361
• Main Authors: Lek, Ngee, Miles, Harriet, Bunch, Trevor, Pilfold-Wilkie, Vickie, Tadokoro-Cuccaro, Rieko, Davies, John, Ong, Ken K, Hughes, Ieuan A
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group 01.04.2014; BMJ Publishing Group Ltd; BMJ Publishing Group LTD
• Subjects: Age; Androgen insensitivity syndrome; Androgen-Insensitivity Syndrome - complications; Androgen-Insensitivity Syndrome - diagnosis; Androgen-Insensitivity Syndrome - genetics; Androgens; Babies; Biological and medical sciences; Birth weight; Birth Weight - genetics; Body Weight; Complications and side effects; Databases, Factual; Diseases of mother, fetus and pregnancy; Disorder of Sex Development, 46,XY - complications; Disorder of Sex Development, 46,XY - diagnosis; Disorder of Sex Development, 46,XY - genetics; Ethics; Fetal growth retardation; Fetal Growth Retardation - etiology; Fetal Growth Retardation - genetics; Fetus; Gene mutation; Gene mutations; General aspects; Genitalia, Male - abnormalities; Genotype & phenotype; Gestational Age; Growth retardation; Gynecology. Andrology. Obstetrics; Histology; Humans; Infant, Newborn; Infants; Influence; Male; Medical sciences; Miscellaneous; Mutation; Phenotype; Pregnancy; Pregnancy. Fetus. Placenta; Prenatal development; Prevention and actions; Public health. Hygiene; Public health. Hygiene-occupational medicine; R&D; Receptors, Androgen - genetics; Research & development; Research and Development; Risk factors; Severity of Illness Index; Statistical Significance; Studies; Young Children; Human; Pediatrics; Intrauterine growth retardation; Pregnancy disorders; Low frequency; Fetal diseases; Gene; Androgen receptor; Genetics; Mutation; Child; Public health; Hormonal receptor
• ISSN: 0003-9888; 1468-2044
• DOI: 10.1136/archdischild-2013-305338

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.