Skip to main content
SpringerLink
Log in

Ambiguous Genitalia and Problems with Sexual Differentiation

  • Chapter
  • First Online:
Common Problems in the Newborn Nursery

  • 954 Accesses

Abstract

Ambiguity of a newborn’s genitalia or clinical situations in which determining the sex of a newborn is not clear represent a true dilemma in the nursery. Ambiguous genitalia are due to under-masculinization of genetic males or virilization of genetic females. Although congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is the most common cause of ambiguous genitalia in a newborn, other causes should be considered after ruling out this inherited adrenal condition. Having a systematic approach to the problem and an understanding of the processes of main genetic factors and sex hormones involved in sex determination and differentiation will help the clinician to better diagnose, counsel, and manage these challenging patients.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Hamerton JL, Canning N, Ray M, et al. A cytogenetic survey of 14,069 newborn infants. I. Incidence of chromosome abnormalities. Clin Genet. 1975;4:223–43.

    Google Scholar 

  2. Blackless M, Charuvastra A, Derryck A, et al. How sexually dimorphic are we? Am J Hum Biol. 2000;12:151–66.

    Article  Google Scholar 

  3. Jost A, Vigier B, Prépin J, Perchellet JP. Studies on sex differentiation in mammals. Recent Prog Horm Res. 1973;29:1–41.

    CAS  PubMed  Google Scholar 

  4. Lee PA, Houk CP, Ahmed SF, Hughes IA. Consensus statement on management of intersex disorders. International consensus conference on intersex. Pediatrics. 2006;118:e488–500.

    Article  Google Scholar 

  5. Eggers S, Sinclair A. Mammalian sex determination–insights from humans and mice. Chromosom Res. 2012;20:215–38.

    Article  CAS  Google Scholar 

  6. Ono M, Harley VR. Disorders of sex development: new genes, new concepts. Nat Rev Endocrinol. 2013;9:79–91.

    Article  CAS  Google Scholar 

  7. Krone N, Dhir V, Ivison HE, Arlt W. Congenital adrenal hyperplasia and P450 oxidoreductase deficiency. Clin Endocrinol. 2007;66:162–72.

    Article  CAS  Google Scholar 

  8. White PC, Speiser PW. Congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Endocr Rev. 2000;21:245–91.

    CAS  PubMed  Google Scholar 

  9. Nordenström A, Ahmed S, Jones J, Coleman M, Price DA, Clayton PE, Hall CM. Female preponderance in congenital adrenal hyperplasia due to CYP21 deficiency in England: implications for neonatal screening. Horm Res. 2005;63:22–8.

    PubMed  Google Scholar 

  10. Pang S, Shook MK. Current status of neonatal screening for congenital adrenal hyperplasia. Curr Opin Pediatr. 1997;9:419–23.

    Article  CAS  Google Scholar 

  11. Therrell BL. Newborn screening for congenital adrenal hyperplasia. Endocrinol Metab Clin N Am. 2001;30:15–30.

    Article  CAS  Google Scholar 

  12. van der Kamp HJ, Wit JM. Neonatal screening for congenital adrenal hyperplasia. Eur J Endocrinol. 2004 Nov;151(Suppl 3):U71–5.

    Article  Google Scholar 

  13. NNSIS 2009 National Newborn Screening Information System. Available at http://www2.uthscsa.edu/nnsis.

  14. Zachmann M, Tassinari D, Prader A. Clinical and biochemical variability of congenital adrenal hyperplasia due to 11β-hydroxylase deficiency: a study of 25 patients. J Clin Endocrinol Metab. 1983;56:222–9.

    Article  CAS  Google Scholar 

  15. Therrell BL Jr, Berenbaum SA, Manter-Kapanke V, Simmank J, Korman K, Prentice L, Gonzalez J, Gunn S. Results of screening 1.9 million Texas newborns for 21-hydroxylase-deficient congenital for 21-hydroxylase-deficient congenital adrenal hyperplasia. Pediatrics. 1998 Apr;101:583–90.

    Article  Google Scholar 

  16. Allen DB, Hoffman GL, Fitzpatrick P, Laessig R, Maby S, Slyper A. Improved precision of newborn screening for congenital adrenal hyperplasia using weight-adjusted criteria for 17-hydroxyprogesterone levels. J Pediatr. 1997;130:128–33.

    Article  CAS  Google Scholar 

  17. al Saedi S, Dean H, Dent W, Stockl E, Cronin C. Screening for congenital adrenal hyperplasia: the Delfia screening test overestimates serum 17-hydroxyprogesterone in preterm infants. Pediatrics. 1996 Jan;97:100–2.

    PubMed  Google Scholar 

  18. Oakes MB, Eyvazzadeh AD, Quint E, Smith YR. Complete androgen insensitivity syndrome—a review. J Pediatr Adolesc Gynecol. 2008 Dec;21(6):305–10. https://doi.org/10.1016/j.jpag.2007.09.006.

    Article  PubMed  Google Scholar 

  19. Hughes IA, Deeb A. Androgen resistance. Best Pract Res Clin Endocrinol Metab 2006;20(4):577–598. PMID 17161333. https://doi.org/10.1016/j.beem.2006.11.003.

    Article  CAS  Google Scholar 

  20. Cools M, Van Aerde K, Kersemaekers AM, et al. Morphological and immunohistochemical differences between gonadal maturation delay and early germ cell neoplasia in patients with undervirilization syndromes. J Clin Endocrinol Metab. 2005 Sep;90(9):5295–303.

    Article  CAS  Google Scholar 

  21. Hannema SE, Scott IS, Rajperts-De Meyts E, Skakkebaek NE, Coleman N, Hughes IA. Testicular development in the complete androgen insensitivity syndrome. J Pathol. 2006;208:518–52.

    Article  CAS  Google Scholar 

  22. Hurt WG, Bodurtha JN, McCall JB, Ali MM, Hurt WG, Bodurtha JN, McCall JB, Ali MM. Seminoma in pubertal patient with androgen insensitivity syndrome. Am J Obstet Gynecol. 1989;161:530–1.

    Article  CAS  Google Scholar 

  23. Page DC. Hypothesis: a Y-chromosomal gene causes gonadoblastoma in dysgenetic gonads. Development. 1987;101:151e5.

    Google Scholar 

  24. McCann-Crosby B, Mansouri R, Dietrich JE, McCullough LB, Sutton VR, Austin EG, et al. State of the art review in gonadal dysgenesis: challenges in diagnosis and management. Int J Pediatr Endocrinol. 2014;2014:4.

    Article  Google Scholar 

  25. Verp MS, Simpson JL. Abnormal sexual differentiation and neoplasia. Cancer Genet Cytogenet. 1987;25:191e218.

    Article  Google Scholar 

  26. Lubahn DB, Joseph DR, Sullivan PM, et al. Cloning of human androgen receptor and complementary DNA and localization to the X chromosome. Science. 1988;240:327.

    Article  CAS  Google Scholar 

  27. Brinkmann AO, Faber PW, Rooij v, et al. The human androgen receptor: domain structure, genomic organization and regulation of expression. J Steroid Biochem. 1989;34:307.

    Article  CAS  Google Scholar 

  28. Houk CP, Lee PA. Consensus statement on terminology and management: disorders of sex development. Sex Dev. 2008;2(4–5):172–80.

    Article  CAS  Google Scholar 

  29. Esoterix endocrinology syllabus. hCG stimulation testing. www.essoterix.com. Available at http://www.esoterix.com/files/Endocrinology_Syllabus_3.22.11.pdf. Accessed 13 May 2014.

  30. Imperato-McGinley J, Peterson RE, Gautier T, Sturla E. Androgens and the evolution of male-gender identity among male pseudohermaphrodites with 5alpha-reductase deficiency. N Engl J Med. 1979 May;300(22):1233–7.

    Article  CAS  Google Scholar 

  31. Saenger P, Goldman AS, Levine LS, et al. Prepubertal diagnosis of steroid 5 alpha-reductase deficiency. J Clin Endocrinol Metab. 1978 Apr;46(4):627–34.

    Article  CAS  Google Scholar 

  32. Hiort O, Sinnecker GH, Willenbring H, Lehners A, Zöllner A, Struve D. Nonisotopic single strand conformation analysis of the 5 alpha-reductase type 2 gene for the diagnosis of 5 alpha-reductase deficiency. J Clin Endocrinol Metab. 1996;81:3415–8.

    CAS  PubMed  Google Scholar 

  33. Okeigwe I, Kuohung W. 5-alpha reductase deficiency: a 40-year retrospective review. Curr Opin Endocrinol Diabetes Obes. 2014;21(6):483–7.

    Article  CAS  Google Scholar 

  34. Hersmus R, Kalfa N, de Leeuw B, et al. FOXL2 and SOX9 as parameters of female and male gonadal differentiation in patients with various forms of disorders of sex development (DSD). J Pathol. 2008;215(1):31–8.

    Article  CAS  Google Scholar 

  35. Barbaro M, Wedell A, Nordenström A. Disorders of sex development. Semin Fetal Neonatal Med. 2011;16(2):119–27.

    Article  CAS  Google Scholar 

  36. Abbas N, McElreavey K, Leconiat M, Vilain E, Jaubert F, Berger R, Nihoul-Fekete C, Rappaport R, Fellous M. Familial case of 46,XX male and 46,XX true hermaphrodite associated with a paternal-derived SRY-bearing X chromosome. C R Arcad Sci III. 1993;316:375–83.

    CAS  Google Scholar 

  37. Hughes IA, Houk C, Ahmed SF, Lee PA. LWPES consensus group, ESPE consensus group consensus statement on management of intersex disorders. Arch Dis Child. 2006;91:554–63.

    Article  CAS  Google Scholar 

  38. Vorona E, Zitzmann M, Gromoll J, Schüring AN, Nieschlag E. Clinical, Endocrinological, and epigenetic features of the 46,XX male syndrome, compared with 47,XXY Klinefelter patients. J Clin Endocrinol Metab. 2007;92:3458–65.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. SUNY/Stony Brook School of Medicine, Stony Brook, NY, USA

    Moris Angulo MD

  2. Division of Genetics, NYU Winthrop Hospital, Mineola, NY, USA

    Moris Angulo MD

Authors
  1. Moris Angulo MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Moris Angulo MD .

Editor information

Editors and Affiliations

  1. Citrus Valley Medical Center, West Covina, CA, USA

    Gilbert I. Martin

  2. Stony Brook University SUNY, Mount Sinai - South Nassau Medical Center, Oceanside, NY, USA

    Warren Rosenfeld

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Angulo, M. (2019). Ambiguous Genitalia and Problems with Sexual Differentiation. In: Martin, G., Rosenfeld, W. (eds) Common Problems in the Newborn Nursery. Springer, Cham. https://doi.org/10.1007/978-3-319-95672-5_19

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-95672-5_19

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-95671-8

  • Online ISBN: 978-3-319-95672-5

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation