Predicting puberty in partial androgen insensitivity syndrome: Use of clinical and functional androgen receptor indices.
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Lek, N., Tadokoro-Cuccaro, R., Whitchurch, J. B., Mazumder, B., Miles, H., Prentice, P., Bunch, T., et al. (2018). Predicting puberty in partial androgen insensitivity syndrome: Use of clinical and functional androgen receptor indices.. EBioMedicine, 36 401-409. https://doi.org/10.1016/j.ebiom.2018.09.047
BACKGROUND: PAIS exhibits a complex spectrum of phenotypes and pubertal outcomes. The paucity of reliable prognostic indicators can confound management decisions including sex-of-rearing. We assessed whether external masculinisation score (EMS) at birth or functional assays correlates with pubertal outcome in PAIS patients and whether the EMS is helpful in sex assignment. METHODS: We collected pubertal outcome data for 27 male-assigned PAIS patients, all with confirmed androgen receptor (AR) mutations, including two previously uncharacterized variants (I899F; Y916C). Patients were grouped as follows; EMS at birth <5 and ≥ 5 (EMS in normal males is 12; median EMS in PAIS is 4·7) and pubertal outcomes compared. FINDINGS: Only 6/9 patients (67%) with EMS <5 underwent spontaneous onset of puberty, versus all 18 patients with EMS ≥5 (p = .03). Only 1/6 patients (17%) with EMS <5 developed adult genitalia reaching Tanner stage 4 or 5, versus 11/13 (85%) with EMS ≥5 (p = 0·01). There was no significant difference between the two groups of patients in being prescribed androgen replacement, who reached adult testicular volume ≥ 15 ml, pubic hair Tanner stage 4 or 5, above average adult height, had gynaecomastia, and mastectomy. No correlation was observed between EMS and in vitro AR function. INTERPRETATION: In PAIS with AR mutation, birth EMS is a simple predictor of spontaneous pubertal onset and satisfactory adult genitalia. This provides useful information when discussing the likely options for management at puberty. FUND: European Commission Framework 7 Programme, NIHR Cambridge Biomedical Research Centre, BBSRC DTP.
Cell Line, Animals, Humans, Androgen-Insensitivity Syndrome, Receptors, Androgen, Gene Expression, Puberty, Genotype, Mutation, Alleles, Adolescent, Adult, Male, Young Adult, Biomarkers
External DOI: https://doi.org/10.1016/j.ebiom.2018.09.047
This record's URL: https://www.repository.cam.ac.uk/handle/1810/285520
Attribution-NonCommercial-NoDerivatives 4.0 International
Licence URL: https://creativecommons.org/licenses/by-nc-nd/4.0/