The Long-Term Outcome of Boys With Partial Androgen Insensitivity Syndrome and a Mutation in the Androgen Receptor Gene

A. Lucas-Herald, S. Bertelloni, A. Juul, J. Bryce, J. Jiang, M. Rodie, R. Sinnott, M. Boroujerdi, M. Lindhardt Johansen, O. Hiort, P. M. Holterhus, M. Cools, G. Guaragna-Filho, G. Guerra-Junior, N. Weintrob, S. Hannema, S. Drop, T. Guran, F. Darendeliler, A. Nordenstrom, I. A. Hughes, C. Acerini, R. Tadokoro-Cuccaro, S. F. Ahmed

In boys with suspected Partial Androgen Insensitivity Syndrome (PAIS), systematic evidence that supports the long-term prognostic value of identifying a mutation in the androgen receptor gene (AR) is lacking. To assess the clinical characteristics and long-term outcomes in young men with suspected PAIS in relation to the results of AR analysis Methods: Through the I-DSD Registry, clinical information was gathered on young men suspected of having PAIS (n=52) who presented before the age of 16 yrs and who had genetic analysis of AR. The median age at presentation and at the time of the study was 1 month (1 day, 16 yrs) and 22 yrs (16, 52), respectively. Of the cohort, 29 (56%) had 20 different AR mutations reported. At diagnosis, the median external masculinisation score (EMS) was 7 and 6 in cases with and without AR mutation, respectively (p=0.9) and median current EMS was 9 and 10, respectively (p=0.28). Thirty-five (67%) men required at least one surgical procedure and those with a mutation were more likely to require multiple surgeries for hypospadias (p=0.004). All cases with an AR mutation had gynecomastia compared to 9% of those without an AR mutation. Of the 6 men who had a mastectomy, 5 (83%) had an AR mutation. Boys with genetically confirmed PAIS are likely to have a poorer clinical outcome than those with XY DSD, normal testosterone synthesis and without an identifiable AR mutation. Routine genetic analysis of AR to confirm PAIS informs long-term prognosis and management.