RT Journal Article
SR Electronic
T1 Low frequency of androgen receptor gene mutations in 46 XY DSD, and fetal growth restriction
JF Archives of Disease in Childhood
JO Arch Dis Child
FD BMJ Publishing Group Ltd and Royal College of Paediatrics and Child Health
SP 358
OP 361
DO 10.1136/archdischild-2013-305338
VO 99
IS 4
A1 Lek, Ngee
A1 Miles, Harriet
A1 Bunch, Trevor
A1 Pilfold-Wilkie, Vickie
A1 Tadokoro-Cuccaro, Rieko
A1 Davies, John
A1 Ong, Ken K
A1 Hughes, Ieuan A
YR 2014
UL http://adc.bmj.com/content/99/4/358.abstract
AB 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.