A Single-Center, Observational Study of 607 Children and Young People Presenting With Differences of Sex Development (DSD)

Elim Man; Imran Mushtaq; Angela Barnicoat; Polly Carmichael; Claire R Hughes; Kate Davies; Helen Aitkenhead; Rakesh Amin; Charles R Buchanan; Abraham Cherian; Nikola J Costa; Sarah M Creighton; Patrick G Duffy; Emma Hewson; Peter C Hindmarsh; Louisa C Monzani; Catherine J Peters; Philip G Ransley; Naima Smeulders; Helen A Spoudeas; Dan Wood; Ieuan A Hughes; Harshini Katugampola; Caroline E Brain; Mehul T Dattani; John C Achermann

doi:10.1210/jendso/bvac165

A Single-Center, Observational Study of 607 Children and Young People Presenting With Differences of Sex Development (DSD)

J Endocr Soc. 2022 Oct 28;7(1):bvac165. doi: 10.1210/jendso/bvac165. eCollection 2022 Nov 17.

Authors

Elim Man^{1

2

3}, Imran Mushtaq⁴, Angela Barnicoat⁵, Polly Carmichael^{6

7}, Claire R Hughes^{2

8}, Kate Davies^{2

9}, Helen Aitkenhead¹⁰, Rakesh Amin², Charles R Buchanan¹¹, Abraham Cherian⁴, Nikola J Costa¹⁰, Sarah M Creighton¹², Patrick G Duffy⁴, Emma Hewson⁶, Peter C Hindmarsh^{2

13}, Louisa C Monzani⁶, Catherine J Peters², Philip G Ransley⁴, Naima Smeulders⁴, Helen A Spoudeas^{1

2}, Dan Wood^{4

14

15}, Ieuan A Hughes¹⁶, Harshini Katugampola², Caroline E Brain², Mehul T Dattani^{1

2}, John C Achermann^{1

2}

Affiliations

¹ Genetics & Genomic Medicine Research and Teaching Department, UCL Great Ormond Street Institute of Child Health, University College London, London WC1N 1EH, UK.
² Department of Endocrinology, Great Ormond Street Hospital NHS Foundation Trust, London WC1N 3JH, UK.
³ Department of Paediatrics & Adolescent Medicine, Hong Kong Children's Hospital, Hong Kong SAR, People's Republic of China.
⁴ Department of Urology, Great Ormond Street Hospital for Children, London WC1N 3JH, UK.
⁵ Department of Clinical Genetics, Great Ormond Street Hospital NHS Foundation Trust, London WC1N 3JH, UK.
⁶ Department of Clinical Psychology, Great Ormond Street Hospital NHS Foundation Trust, London WC1N 3JH, UK.
⁷ Gender Identity Development Service, Tavistock and Portman NHS Foundation Trust, London NW3 5BA, UK.
⁸ Centre for Endocrinology, William Harvey Research Institute, Queen Mary University of London, London EC1M 6BQ, UK.
⁹ Institute of Health and Social Care, London South Bank University, London SE1 0AA, UK.
¹⁰ Department of Chemical Pathology, Great Ormond Street Hospital NHS Foundation Trust, London WC1N 3JH, UK.
¹¹ Department of Child Health, King's College Hospital NHS Foundation Trust, London SE5 9RS, UK.
¹² Institute for Women's Health, University College London Hospitals NHS Foundation Trust, London NW1 2BU, UK.
¹³ Department of Paediatrics, University College London Hospitals NHS Foundation Trust, London NW1 2BU, UK.
¹⁴ Department of Urology, University College London Hospitals NHS Foundation Trust, London NW1 2BU, UK.
¹⁵ Department of Urology, Children's Hospital Colorado and University of Colorado, Aurora, Colorado 80045, USA.
¹⁶ Department of Paediatrics, University of Cambridge, Cambridge CB2 0QQ, UK.

Abstract

Context: Differences of sex development (DSD) represent a wide range of conditions presenting at different ages to various health professionals. Establishing a diagnosis, supporting the family, and developing a management plan are important.

Objective: We aimed to better understand the presentation and prevalence of pediatric DSD.

Methods: A retrospective, observational cohort study was undertaken in a single tertiary pediatric center of all children and young people (CYP) referred to a DSD multidisciplinary team over 25 years (1995-2019). In total, 607 CYP (520 regional referrals) were included. Data were analyzed for diagnosis, sex-assignment, age and mode of presentation, additional phenotypic features, mortality, and approximate point prevalence.

Results: Among the 3 major DSD categories, sex chromosome DSD was diagnosed in 11.2% (68/607) (most commonly 45,X/46,XY mosaicism), 46,XY DSD in 61.1% (371/607) (multiple diagnoses often with associated features), while 46,XX DSD occurred in 27.7% (168/607) (often 21-hydroxylase deficiency). Most children (80.1%) presented as neonates, usually with atypical genitalia, adrenal insufficiency, undescended testes or hernias. Those presenting later had diverse features. Rarely, the diagnosis was made antenatally (3.8%, n = 23) or following incidental karyotyping/family history (n = 14). Mortality was surprisingly high in 46,XY children, usually due to complex associated features (46,XY girls, 8.3%; 46,XY boys, 2.7%). The approximate point prevalence of neonatal referrals for investigation of DSD was 1 in 6347 births, and 1 in 5101 overall throughout childhood.

Conclusion: DSD represent a diverse range of conditions that can present at different ages. Pathways for expert diagnosis and management are important to optimize care.

Keywords: DSD; ambiguous genitalia; androgen insensitivity; congenital adrenal hyperplasia; hypospadias; sex development; testicular dysgenesis.