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Highlights & Basics
- Atypical genitalia (i.e., a genital phenotype that is neither clearly male nor female) are caused by the atypical development of chromosomal, gonadal, or anatomical sex. The complex group of disorders that cause atypical genitalia are called differences of sex development (DSD).
- Sex chromosome DSD results from the atypical complement of sex chromosomes, and includes syndromes such as Turner syndrome (45,X with one absent sex chromosome) and Klinefelter syndrome (XXY with one additional X chromosome). Mosaicism occurs when more than one type of chromosomal arrangement is present (e.g., 45,X/46,XY).
- 46,XX DSD are conditions characterized by excess exposure to androgens. Over 95% of causes of atypical genitalia with a 46,XX genotype are due to congenital adrenal hyperplasia secondary to 21 hydroxylase deficiency.
- 46,XY DSD can be due to several etiologies and usually requires a more extensive diagnostic evaluation.
- The initial management of a neonate with atypical genitalia is a social and clinical emergency. The local team has a key role in coordinating the initial assessment and investigations, and supporting parents. It is important there is early discussion with a more specialist multidisciplinary team with expertise in pediatric endocrinology, genetics, and surgery, and with appropriate psychiatric/psychological support. For many DSDs, long-term surgical and psychosexual outcomes remain uncertain.
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Images
Infant presenting with ambiguous genitalia; the history and appearance are most likely consistent with mixed gonadal dysgenesis
Infant presenting with ambiguous genitalia; history and appearance are most likely consistent with congenital adrenal hyperplasia, due to 21 hydroxylase deficiency
Examples of genes that control different stages of sex determination; ovarian determining genes are the subject of ongoing research
Schematic representation of sex differentiation. Glossary: 5 alpha-reductase (5alpha-R), anti-Müllerian hormone (AMH), dihydrotestosterone (DHT)
Selected examples of abnormal testosterone production (red) or testosterone action (purple) in 46,XY differences of sex development. Glossary: 3 beta-hydroxysteroid dehydrogenase deficiency (3beta-HSD), 17 alpha-hydroxylase deficiency (17alpha-HSD), 17 beta-hydroxysteroid dehydrogenase deficiency (17beta-HSD), androgen receptor (AR), complete androgen insensitivity (CAIS), partial androgen insensitivity (PAIS)
Selected examples of causes of androgen excess in 46,XX differences of sex development
External masculinization score
Citations
Lee PA, Nordenström A, Houk CP, et al. Global disorders of sex development update since 2006: perceptions, approach and care. Horm Res Paediatr. 2016 Jan 28;85(3):158-80.[Abstract][Full Text]
Cools M, Nordenström A, Robeva R, et al. Caring for individuals with a difference of sex development (DSD): a Consensus Statement. Nat Rev Endocrinol. 2018 Jul;14(7):415-29.[Abstract][Full Text]
MacLaughlin DT, Donahoe PK. Sex determination and differentiation. N Engl J Med. 2004 Jan 22;350(4):367-78.[Abstract]
Lambert SM, Vilain EJ, Kolon TF. A practical approach to ambiguous genitalia in the newborn period. Urol Clin North Am. 2010 May;37(2):195-205.[Abstract]
Davies JH, Cheetham T. Recognition and assessment of atypical and ambiguous genitalia in the newborn. Arch Dis Child. 2017 Apr 25 [Epub ahead of print].[Abstract]
Chavhan GB, Parra DA, Oudjhane K, et al. Imaging of ambiguous genitalia: classification and diagnostic approach. Radiographics. 2008 Nov-Dec;28(7):1891-904.[Abstract]
Brain CE, Creighton SM, Mushtaq I, et al. Holistic management of DSD. Best Pract Res Clin Endocrinol Metab. 2010 Apr;24(2):335-54.[Abstract][Full Text]
Mieszczak J, Houk CP, Lee PA. Assignment of the sex of rearing in the neonate with a disorder of sex development. Curr Opin Pediatr. 2009 Aug;21(4):541-7.[Abstract]
1. Lee PA, Nordenström A, Houk CP, et al. Global disorders of sex development update since 2006: perceptions, approach and care. Horm Res Paediatr. 2016 Jan 28;85(3):158-80.[Abstract][Full Text]
2. Cools M, Nordenström A, Robeva R, et al. Caring for individuals with a difference of sex development (DSD): a Consensus Statement. Nat Rev Endocrinol. 2018 Jul;14(7):415-29.[Abstract][Full Text]
3. Blackless M, Charuvastra A, Derryck A, et al. How sexually dimorphic are we?: review and synthesis. Am J Hum Biol. 2000 Mar;12(2):151-166.[Abstract]
4. Ahmed SF, Dobbie R, Finlayson AR, et al. Prevalence of hypospadias and other genital anomalies among singleton births, 1988-1997, in Scotland. Arch Dis Child Fetal Neonatal Ed. 2004 Mar;89(2):F149-51.[Abstract][Full Text]
5. Rodie ME, Ali SR, Jayasena A, et al. A nationwide study of the prevalence and initial management of atypical genitalia in the newborn in Scotland. Sex Dev. 2022;16(1):11-8.[Abstract][Full Text]
6. Moreno-Garcia M, Miranda EB. Chromosomal anomalies in cryptorchidism and hypospadias. J Urol. 2002 Nov;168(5):2170-2; discussion 2172.[Abstract][Full Text]
7. Ahmed SF, Achermann J, Alderson J, 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 Dec;95(6):818-40.[Abstract][Full Text]
8. Morel Y, Rey R, Teinturier C, et al. Aetiological diagnosis of male sex ambiguity: a collaborative study. Eur J Pediatr. 2002 Jan;161(1):49-59.[Abstract]
9. Siklar Z, Berberoglu M, Adiyaman P, et al. Disorders of gonadal development: a broad clinical, cytogenetic and histopathologic spectrum. Pediatr Endocrinol Rev. 2007 Mar;4(3):210-7.[Abstract]
10. MacLaughlin DT, Donahoe PK. Sex determination and differentiation. N Engl J Med. 2004 Jan 22;350(4):367-78.[Abstract]
11. Giwercman YL, Svensson J. Androgen insensitivity syndrome [article in Norwegian]. Tidsskr Nor Laegeforen. 2008 Feb 28;128(5):581-5.[Abstract]
12. Grumbach MM. A window of opportunity: the diagnosis of gonadotropin deficiency in the male infant. J Clin Endocrinol Metab. 2005 May;90(5):3122-7.[Abstract][Full Text]
13. Iovane A, Aumas C, de Roux N. New insights in the genetics of isolated hypogonadotropic hypogonadism. Eur J Endocrinol. 2004 Nov;151 Suppl 3:U83-8.[Abstract]
14. MacGillivray MH, Mazur T. Intersex. Adv Pediatr. 2005;52:295-319.[Abstract]
15. Heland S, Hewitt JK, McGillivray G, et al. Preventing female virilisation in congenital adrenal hyperplasia: the controversial role of antenatal dexamethasone. Aust N Z J Obstet Gynaecol. 2016 Jun;56(3):225-32.[Abstract]
16. Hirvikoski T, Nordenström A, Wedell A, et al. Prenatal dexamethasone treatment of children at risk for congenital adrenal hyperplasia: the Swedish experience and standpoint. J Clin Endocrinol Metab. 2012 Jun;97(6):1881-3.[Abstract][Full Text]
17. Parisi MA, Ramsdell LA, Burns MW, et al. A gender assessment team: experience with 250 patients over a period of 25 years. Genet Med. 2007 Jun;9(6):348-57.[Abstract]
18. Guerra-Júnior G, Maciel-Guerra AT. The role of the pediatrician in the management of children with genital ambiguities. J Pediatr (Rio J). 2007 Nov;83(5 Suppl):S184-91.[Abstract]
19. Lambert SM, Vilain EJ, Kolon TF. A practical approach to ambiguous genitalia in the newborn period. Urol Clin North Am. 2010 May;37(2):195-205.[Abstract]
20. Davies JH, Cheetham T. Recognition and assessment of atypical and ambiguous genitalia in the newborn. Arch Dis Child. 2017 Apr 25 [Epub ahead of print].[Abstract]
21. Ahmed SF, Achermann JC, Arlt W, 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 May;84(5):771-88.[Abstract][Full Text]
22. Ahmed SF, Khwaja O, Hughes IA. The role of a clinical score in the assessment of ambiguous genitalia. BJU Int 2000 Jan;85(1):120-4.[Abstract][Full Text]
23. van der Straaten S, Springer A, Zecic A, et al. The external genitalia score (EGS): A European Multicenter Validation Study. J Clin Endocrinol Metab. 2020 Mar 1;105(3):.[Abstract][Full Text]
24. Tuladhar R, Davis PG, Batch J, et al. Establishment of a normal range of penile length in preterm infants. J Paediatr Child Health. 1998 Oct;34(5):471-3.[Abstract]
25. Ahmed SF, Bashamboo A, Lucas-Herald A, et al. Understanding the genetic aetiology in patients with XY DSD. Br Med Bull. 2013;106:67-89.[Abstract][Full Text]
26. American College of Medical Genetics and Genomics. Five things physicians and patients should question. Choosing Wisely, an initiative of the ABIM Foundation. 2021 [internet publication].[Full Text]
27. Chavhan GB, Parra DA, Oudjhane K, et al. Imaging of ambiguous genitalia: classification and diagnostic approach. Radiographics. 2008 Nov-Dec;28(7):1891-904.[Abstract]
28. European Association of Urology; European Society for Paediatric Urology. Guidelines on paediatric urology. 2019 [internet publication].[Full Text]
29. El-Sherbiny M. Disorders of sexual differentiation: II. Diagnosis and treatment. Arab J Urol. 2013;11:27-32.[Full Text]
30. Brain CE, Creighton SM, Mushtaq I, et al. Holistic management of DSD. Best Pract Res Clin Endocrinol Metab. 2010 Apr;24(2):335-54.[Abstract][Full Text]
31. Mieszczak J, Houk CP, Lee PA. Assignment of the sex of rearing in the neonate with a disorder of sex development. Curr Opin Pediatr. 2009 Aug;21(4):541-7.[Abstract]
32. Fallat ME, Donahoe PK. Intersex genetic anomalies with malignant potential. Curr Opin Pediatr. 2006 Jun;18(3):305-11.[Abstract]
33. BMJ Best Practice. Congenital adrenal hyperplasia. Jul 2016 [internet publication].[Full Text]
34. Palmer BW, Wisniewski AB, Schaeffer TL, et al. A model of delivering multi-disciplinary care to people with 46 XY DSD. J Pediatr Urol. 2012 Feb;8(1):7-16.[Abstract]
