Clinical Spectrum of Disorders of Sexual Differentiation in Children

Zarka  Batool; Hina  Sattar; Haniyah  Anwar; Shayan  Saeed; Aneela  Mahmood; Iqra  Mushtaq

doi:10.54112/bcsrj.v6i6.1970

Authors

Zarka Batool Department of Pediatrics Medicine, Benazir Bhutto Hospital, Rawalpindi, Pakistan
Hina Sattar Department of Pediatric Medicine, Rawalpindi Medical University, Rawalpindi, Pakistan
Haniyah Anwar Department of Pediatrics Medicine PIMS Islamabad, Pakistan
Shayan Saeed Department of Pediatrics Medicine PIMS Islamabad, Pakistan
Aneela Mahmood Department of Pediatrics Medicine PIMS Islamabad, Pakistan
Iqra Mushtaq Department of Pediatrics Medicine, PNS Hafeez Hospital, Islamabad, Pakistan

DOI:

https://doi.org/10.54112/bcsrj.v6i6.1970

Keywords:

Disorders of sexual differentiation, ambiguous genitalia, congenital adrenal hyperplasia, androgen insensitivity syndrome

Abstract

Disorders of sexual differentiation (DSD) are a heterogeneous group of congenital conditions characterized by atypical development of chromosomal, gonadal, or anatomical sex. Objective: To evaluate the clinical spectrum, modes of presentation, and underlying etiologies of DSD in children presenting with ambiguous genitalia. Methods: This cross-sectional study was conducted at the Department of Pediatrics, Rawalpindi Medical University (RMU) and Allied Hospitals from August 2023 to July 2024. A total of 110 children aged from birth to 12 years with ambiguous genitalia were enrolled using non-probability consecutive sampling. Data were collected using a predesigned proforma, including detailed history, physical examination, External Masculinization Score (EMS), and Prader staging for 46 XX cases. Results: The mean age at presentation was 3.8 ± 2.9 years, with 62.7% presenting in infancy. Ambiguous genitalia at birth was the most common mode of presentation (65.5%), followed by inguinal/labial swellings (16.4%). Among 46 XY patients (n=64), androgen insensitivity syndrome (28.1%) and 5-α reductase deficiency (18.8%) were the most frequent causes. In 46 XX patients (n=46), congenital adrenal hyperplasia was predominant (73.9%), with ovotesticular DSD accounting for 17.4%. Most 46 XX patients exhibited moderate to severe virilization (Prader stages III–IV). The mean EMS across all patients was 5.4 ± 2.3, consistent with the presence of genital ambiguity. Conclusion: DSD in children most commonly presents at birth with ambiguous genitalia, with AIS and CAH being the leading etiologies among 46 XY and 46 XX patients, respectively. The high proportion of severe genital ambiguity reflects delays in referral and Diagnosis.

Downloads

Download data is not yet available.

References

Amolo P, Laigong P, Omer A, Drop S. Etiology and clinical presentation of disorders of sex development in Kenyan children and adolescents. Int J Endocrinol. 2019;2019:2985471.

García-Acero M, Moreno O, Suárez F, Rojas A. Disorders of sexual development: current status and progress in the diagnostic approach. Curr Urol. 2020;13(4):169–78. https://doi.org/10.1159/000499274

León NY, Reyes AP, Harley VR. A clinical algorithm to diagnose differences of sex development. Lancet Diabetes Endocrinol. 2019;7(7):560–74. https://doi.org/10.1016/S2213-8587(18)30339-5

Witchel SF. Disorders of sex development. Best Pract Res Clin Obstet Gynaecol. 2018;48:90–102. https://doi.org/10.1016/j.bpobgyn.2017.11.005

Correya MA, Babu R, Archana B, Ravirajendiran S. Disorders of sexual differentiation. Indian J Pathol Microbiol. 2021;64(4):?–?. https://doi.org/10.4103/IJPM.IJPM_358_20

Hughes IA, Houk CP, Ahmed SF, Lee PA; LWPES/ESPE Consensus Group. Consensus statement on management of intersex disorders. Arch Dis Child. 2006;91(7):554–63. https://doi.org/10.1136/adc.2006.098319

Cools M, Nordenström A, Robeva R, Hall J, Hall H, Looijenga LHJ, et al. Caring for individuals with a difference of sex development (DSD): a consensus statement. Nat Rev Endocrinol. 2018;14(7):415–29. https://doi.org/10.1038/s41574-018-0010-8

Acién P, Acién M. Disorders of sex development: classification, review, and impact on fertility. J Clin Med. 2020;9(11):3555. https://doi.org/10.3390/jcm9113555

Kazmi D, Bailey J, Yau M, Abu-Amer W, Kumar A, Low M, et al. New developments in prenatal diagnosis of congenital adrenal hyperplasia. J Steroid Biochem Mol Biol. 2016;165(Pt A):94–101. https://doi.org/10.1016/j.jsbmb.2016.06.016

Manzoor J, Afraab S, Yaqoob M. Ambiguous genitalia: seven years’ experience from a tertiary care hospital. Pak J Med Sci. 2019;35(5):1180–5. https://doi.org/10.12669/pjms.35.5.1180

Su R, Adam MP, Ramsdell L, Fechner PY, Shnorhavorian M. External masculinization score and genetic testing in 46,XY DSD. AIMS Genet. 2015;2(2):163–?. https://doi.org/10.3934/genet.2015.2.163

Al-Sahar NF, Al-Ali AJ, Mansour AA. Spectrum of disorders of sex development: a single-center experience in the southern area of Iraq. Cureus. 2024;16(8):e67571. https://doi.org/10.7759/cureus.67571

Ahmed SF, Achermann JC, Arlt W, Balen A, Conway G, Edwards Z, et al. Society for Endocrinology UK guidance on the initial evaluation of an infant or an adolescent with a suspected disorder of sex development (revised 2015). Clin Endocrinol (Oxf). 2016;84(5):771–88. https://doi.org/10.1111/cen.12857

Ahmed SF, Achermann J, Alderson J, Crouch NS, Elford S, Hughes IA, et al. Society for Endocrinology UK guidance on the initial evaluation of a suspected difference or disorder of sex development (revised 2021). Clin Endocrinol (Oxf). 2021;95(6):818–40. https://doi.org/10.1111/cen.14528

Byne W, Karasic DH, Coleman E, Eyler AE, Kidd JD, Meyer-Bahlburg HFL, et al. Gender dysphoria in adults: an overview and primer for psychiatrists. Transgend Health. 2018;3(1):57–70. https://doi.org/10.1089/trgh.2017.0053

Man E, Mushtaq I, Barnicoat A, Carmichael P, Hughes CR, Davies K, et al. A single-center, observational study of 607 children and young people presenting with differences of sex development (DSD). J Endocr Soc. 2023;7(1):bvac165. https://doi.org/10.1210/jendso/bvac165

Zitzmann M, Aksglaede L, Corona G, Isidori AM, Juul A, T’Sjoen G, et al. European Academy of Andrology guidelines on Klinefelter syndrome. Andrology. 2021;9(1):145–67. https://doi.org/10.1111/andr.12909

Speiser PW, Arlt W, Auchus RJ, Baskin LS, Conway GS, Merke DP, et al. Congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2018;103(11):4043–88. https://doi.org/10.1210/jc.2018-01865

Hassan M, Atrushi A. A prospective study on disorders of sex development in Duhok City, Kurdistan Region, Iraq: genetic, etiology, and clinical presentation. Cell Mol Biol (Noisy-le-grand). 2023;69(13):65–9. https://doi.org/10.14715/cmb/2023.69.13.10

Ata A, Özen S, Onay H, Uzun S, Gökşen D, Özkınay F, et al. A large cohort of disorders of sex development and their genetic characteristics: six novel mutations in known genes. Eur J Med Genet. 2021;64(3):104154. https://doi.org/10.1016/j.ejmg.2021.104154

Deeb A, Khamis M, Sayed SA, Magdy Omar O, Odeh R, Ladjouze A, Ameri EA. Sex assignment practice in disorders of sexual differentiation: survey results from paediatric endocrinologists in the Arab region. J Pediatr Endocrinol Metab. 2019;32(1):75–82. https://doi.org/10.1515/jpem-2018-0323