UpToDate
Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate®

Management of the infant with atypical genitalia (disorder of sex development)

Authors
Christopher P Houk, MD
Laurence S Baskin, MD, FAAP
Lynne L Levitsky, MD
Section Editor
Mitchell E Geffner, MD
Deputy Editor
Alison G Hoppin, MD

INTRODUCTION

Individuals with a congenital discrepancy between external genitalia and gonadal and chromosomal sex are classified as having a disorder of sex development (DSD) [1]. Abnormalities sufficient to prompt evaluation (excluding uncomplicated cases of cryptorchidism and hypospadias) occur in approximately one in 1000 to 4500 live births [2-5].

The birth of an infant with atypical genitalia presents a unique set of challenging management issues. This is because psychosexual development is influenced by multiple factors including the genes involved in sexual development, gender differences in brain structure, prenatal androgen exposure, societal and cultural factors, and family dynamics. In the past, decisions about sex of rearing were usually based on potential for reproduction and traditional sexual function and were often accompanied by irreversible genital surgery [6-8]. Long-term outcome data are now available to help predict gender identity for many infants with DSDs, and provide insight into appropriate early management decisions [9-13]. Nonetheless, there is ongoing controversy about some aspects of management, especially for certain types of DSDs for which gender identity remain unpredictable. Thus, uncertainties about adult outcome, gender of rearing, and timing of surgery should contribute to discussions and informed decision making by the parents. Each child and family will have unique characteristics so that all decisions should be made on a case-by-case basis.

The management of infants with clinically significant DSD will be discussed here. The evaluation of these infants is discussed separately. (See "Evaluation of the infant with atypical genitalia (disorder of sex development)".)

TERMINOLOGY

Although the term DSD has been accepted by the medical community, patients and support groups question its usefulness and appropriateness based on three criticisms: first, that DSD is an overly broad term that applies to conditions in which no sexual/gender disruption is expected (eg, Turner syndrome, Trisomy X, and others); second, that this broad term lacks sufficient specificity to be helpful diagnostically; and third, that the use of the word 'disorder' is seen as pejorative by some. Many of these groups do not accept the DSD designation and feel that it should be abandoned by the medical community.

Until a consensus is reached on this issue, we will use the term DSD but will employ it only in relation to those patients in whom there is altered physical sexual differentiation (conditions previously captured by the term "intersex"). Many of these individuals present as newborns with an atypical genital appearance previously termed "ambiguous genitalia." We will not use DSD to refer to conditions in which genital/gender discordance is not expected, such as Klinefelter syndrome, undescended testes, or all but the most severe forms of hypospadias. In many patients who present with atypical genitalia it is now possible to make an accurate diagnosis in a timely fashion, thereby avoiding the use of the term DSD.

                              

Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Dec 2016. | This topic last updated: Tue Dec 20 00:00:00 GMT+00:00 2016.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2017 UpToDate, Inc.
References
Top
  1. Lee PA, Houk CP, Ahmed SF, et al. Consensus statement on management of intersex disorders. International Consensus Conference on Intersex. Pediatrics 2006; 118:e488.
  2. Hughes IA, Nihoul-Fékété C, Thomas B, Cohen-Kettenis PT. Consequences of the ESPE/LWPES guidelines for diagnosis and treatment of disorders of sex development. Best Pract Res Clin Endocrinol Metab 2007; 21:351.
  3. Blackless M, Charuvastra A, Derryck A, et al. How sexually dimorphic are we? Review and synthesis. Am J Hum Biol 2000; 12:151.
  4. Thyen U, Lanz K, Holterhus PM, Hiort O. Epidemiology and initial management of ambiguous genitalia at birth in Germany. Horm Res 2006; 66:195.
  5. Sax L. How common is intersex? a response to Anne Fausto-Sterling. J Sex Res 2002; 39:174.
  6. Reiner WG. Assignment of sex in neonates with ambiguous genitalia. Curr Opin Pediatr 1999; 11:363.
  7. Daaboul J, Frader J. Ethics and the management of the patient with intersex: a middle way. J Pediatr Endocrinol Metab 2001; 14:1575.
  8. Meyer-Bahlburg HF. Gender and sexuality in classic congenital adrenal hyperplasia. Endocrinol Metab Clin North Am 2001; 30:155.
  9. Köhler B, Kleinemeier E, Lux A, et al. Satisfaction with genital surgery and sexual life of adults with XY disorders of sex development: results from the German clinical evaluation study. J Clin Endocrinol Metab 2012; 97:577.
  10. Callens N, van der Zwan YG, Drop SL, et al. Do surgical interventions influence psychosexual and cosmetic outcomes in women with disorders of sex development? ISRN Endocrinol 2012; 2012:276742.
  11. Fagerholm R, Mattila AK, Roine RP, et al. Mental health and quality of life after feminizing genitoplasty. J Pediatr Surg 2012; 47:747.
  12. Callens N, De Cuypere G, Wolffenbuttel KP, et al. Long-term psychosexual and anatomical outcome after vaginal dilation or vaginoplasty: a comparative study. J Sex Med 2012; 9:1842.
  13. Schweizer K, Franziska B, Handford C, Richter-Appelt H. Gender experience and satisfaction with gender allocation in adults with diverse intersex conditions (divergences of sex development, DSD). Psychology and Sexuality 2014; 5:56.
  14. Speiser PW. Congenital adrenal hyperplasia owing to 21-hydroxylase deficiency. Endocrinol Metab Clin North Am 2001; 30:31.
  15. Diamond M, Sigmundson HK. Management of intersexuality. Guidelines for dealing with persons with ambiguous genitalia. Arch Pediatr Adolesc Med 1997; 151:1046.
  16. Douglas G, Axelrad ME, Brandt ML, et al. Consensus in Guidelines for Evaluation of DSD by the Texas Children's Hospital Multidisciplinary Gender Medicine Team. Int J Pediatr Endocrinol 2010; 2010:919707.
  17. Pasterski V, Prentice P, Hughes IA. Impact of the consensus statement and the new DSD classification system. Best Pract Res Clin Endocrinol Metab 2010; 24:187.
  18. Moran ME, Karkazis K. Developing a multidisciplinary team for disorders of sex development: planning, implementation, and operation tools for care providers. Adv Urol 2012; 2012:604135.
  19. 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; 8:7.
  20. Moshiri M, Chapman T, Fechner PY, et al. Evaluation and management of disorders of sex development: multidisciplinary approach to a complex diagnosis. Radiographics 2012; 32:1599.
  21. Gillam LH, Hewitt JK, Warne GL. Ethical principles for the management of infants with disorders of sex development. Horm Res Paediatr 2010; 74:412.
  22. Meyer-Bahlburg HF, Dolezal C, Baker SW, New MI. Sexual orientation in women with classical or non-classical congenital adrenal hyperplasia as a function of degree of prenatal androgen excess. Arch Sex Behav 2008; 37:85.
  23. Meyer-Bahlburg HF, Dolezal C, Baker SW, et al. Gender development in women with congenital adrenal hyperplasia as a function of disorder severity. Arch Sex Behav 2006; 35:667.
  24. Dessens AB, Slijper FM, Drop SL. Gender dysphoria and gender change in chromosomal females with congenital adrenal hyperplasia. Arch Sex Behav 2005; 34:389.
  25. Warne GL. Long-term outcome of disorders of sex development. Sex Dev 2008; 2:268.
  26. González R, Ludwikowski BM. Should CAH in Females Be Classified as DSD? Front Pediatr 2016; 4:48.
  27. Diamond M, Garland J. Evidence regarding cosmetic and medically unnecessary surgery on infants. J Pediatr Urol 2014; 10:2.
  28. Binet A, Lardy H, Geslin D, et al. Should we question early feminizing genitoplasty for patients with congenital adrenal hyperplasia and XX karyotype? J Pediatr Surg 2016; 51:465.
  29. Nordenskjöld A, Holmdahl G, Frisén L, et al. Type of mutation and surgical procedure affect long-term quality of life for women with congenital adrenal hyperplasia. J Clin Endocrinol Metab 2008; 93:380.
  30. Wisniewski AB, Migeon CJ, Malouf MA, Gearhart JP. Psychosexual outcome in women affected by congenital adrenal hyperplasia due to 21-hydroxylase deficiency. J Urol 2004; 171:2497.
  31. Eckoldt-Wolke F. Timing of surgery for feminizing genitoplasty in patients suffering from congenital adrenal hyperplasia. Endocr Dev 2014; 27:203.
  32. Lee PA, Houk CP. Commentary to 'Evidence regarding cosmetic and medically unnecessary surgery on infants'. J Pediatr Urol 2014; 10:7.
  33. Lee PA, Nordenström A, Houk CP, et al. Global Disorders of Sex Development Update since 2006: Perceptions, Approach and Care. Horm Res Paediatr 2016; 85:158.
  34. Schnitzer JJ, Donahoe PK. Surgical treatment of congenital adrenal hyperplasia. Endocrinol Metab Clin North Am 2001; 30:137.
  35. Houk CP, Hughes IA, Ahmed SF, et al. Summary of consensus statement on intersex disorders and their management. International Intersex Consensus Conference. Pediatrics 2006; 118:753.
  36. Chowdhury TK, Laila K, Hutson JM, Banu T. Male gender identity in children with 46,XX DSD with congenital adrenal hyperplasia after delayed presentation in mid-childhood. J Pediatr Surg 2015; 50:2060.
  37. Lee PA, Houk CP. Review of Outcome Information in 46,XX Patients with Congenital Adrenal Hyperplasia Assigned/Reared Male: What Does It Say about Gender Assignment? Int J Pediatr Endocrinol 2010; 2010:982025.
  38. Houk CP, Lee PA. Approach to assigning gender in 46,XX congenital adrenal hyperplasia with male external genitalia: replacing dogmatism with pragmatism. J Clin Endocrinol Metab 2010; 95:4501.
  39. Salle JL, Lorenzo AJ, Jesus LE, et al. Surgical treatment of high urogenital sinuses using the anterior sagittal transrectal approach: a useful strategy to optimize exposure and outcomes. J Urol 2012; 187:1024.
  40. Ludwikowski BM, González R. The Surgical Correction of Urogenital Sinus in Patients with DSD: 15 Years after Description of Total Urogenital Mobilization in Children. Front Pediatr 2013; 1:41.
  41. Merke DP, Poppas DP. Management of adolescents with congenital adrenal hyperplasia. Lancet Diabetes Endocrinol 2013; 1:341.
  42. Yankovic F, Cherian A, Steven L, et al. Current practice in feminizing surgery for congenital adrenal hyperplasia; a specialist survey. J Pediatr Urol 2013; 9:1103.
  43. Suorsa KI, Mullins AJ, Tackett AP, et al. Characterizing Early Psychosocial Functioning of Parents of Children with Moderate to Severe Genital Ambiguity due to Disorders of Sex Development. J Urol 2015; 194:1737.
  44. Baskin LS. Fetal genital anatomy reconstructive implications. J Urol 1999; 162:527.
  45. Kalfa N, Liu B, Klein O, et al. Genomic variants of ATF3 in patients with hypospadias. J Urol 2008; 180:2183.
  46. Martinerie L, Morel Y, Gay CL, et al. Impaired puberty, fertility, and final stature in 45,X/46,XY mixed gonadal dysgenetic patients raised as boys. Eur J Endocrinol 2012; 166:687.
  47. Szarras-Czapnik M, Lew-Starowicz Z, Zucker KJ. A psychosexual follow-up study of patients with mixed or partial gonadal dysgenesis. J Pediatr Adolesc Gynecol 2007; 20:333.
  48. Timing of elective surgery on the genitalia of male children with particular reference to the risks, benefits, and psychological effects of surgery and anesthesia. American Academy of Pediatrics. Pediatrics 1996; 97:590.
  49. Pleskacova J, Hersmus R, Oosterhuis JW, et al. Tumor risk in disorders of sex development. Sex Dev 2010; 4:259.
  50. Cools M, Pleskacova J, Stoop H, et al. Gonadal pathology and tumor risk in relation to clinical characteristics in patients with 45,X/46,XY mosaicism. J Clin Endocrinol Metab 2011; 96:E1171.
  51. Kolesinska Z, Ahmed SF, Niedziela M, et al. Changes over time in sex assignment for disorders of sex development. Pediatrics 2014; 134:e710.
  52. Reiner WG, Gearhart JP, Jeffs R. Psychosexual dysfunction in males with genital anomalies: late adolescence, Tanner stages IV to VI. J Am Acad Child Adolesc Psychiatry 1999; 38:865.
  53. Cohen-Kettenis PT. Gender change in 46,XY persons with 5alpha-reductase-2 deficiency and 17beta-hydroxysteroid dehydrogenase-3 deficiency. Arch Sex Behav 2005; 34:399.
  54. Meyer-Bahlburg HF. Gender monitoring and gender reassignment of children and adolescents with a somatic disorder of sex development. Child Adolesc Psychiatr Clin N Am 2011; 20:639.
  55. Mazur T. Gender dysphoria and gender change in androgen insensitivity or micropenis. Arch Sex Behav 2005; 34:411.
  56. Migeon CJ, Wisniewski AB, Gearhart JP, et al. Ambiguous genitalia with perineoscrotal hypospadias in 46,XY individuals: long-term medical, surgical, and psychosexual outcome. Pediatrics 2002; 110:e31.
  57. Hughes IA, Davies JD, Bunch TI, et al. Androgen insensitivity syndrome. Lancet 2012; 380:1419.
  58. Wünsch L, Holterhus PM, Wessel L, Hiort O. Patients with disorders of sex development (DSD) at risk of gonadal tumour development: management based on laparoscopic biopsy and molecular diagnosis. BJU Int 2012; 110:E958.
  59. Cools M, Looijenga LH, Wolffenbuttel KP, T'Sjoen G. Managing the risk of germ cell tumourigenesis in disorders of sex development patients. Endocr Dev 2014; 27:185.
  60. Abacı A, Çatlı G, Berberoğlu M. Gonadal malignancy risk and prophylactic gonadectomy in disorders of sexual development. J Pediatr Endocrinol Metab 2015; 28:1019.
  61. Verkauskas G, Jaubert F, Lortat-Jacob S, et al. The long-term followup of 33 cases of true hermaphroditism: a 40-year experience with conservative gonadal surgery. J Urol 2007; 177:726.
  62. Sircili MH, Denes FT, Costa EM, et al. Long-term followup of a large cohort of patients with ovotesticular disorder of sex development. J Urol 2014; 191:1532.
  63. Schultz BA, Roberts S, Rodgers A, Ataya K. Pregnancy in true hermaphrodites and all male offspring to date. Obstet Gynecol 2009; 113:534.
  64. van Niekerk WA, Retief AE. The gonads of human true hermaphrodites. Hum Genet 1981; 58:117.
  65. Slijper FM, Drop SL, Molenaar JC, de Muinck Keizer-Schrama SM. Long-term psychological evaluation of intersex children. Arch Sex Behav 1998; 27:125.
  66. Chan-Cua S, Freidenberg G, Jones KL. Occurrence of male phenotype in genotypic females with congenital virilizing adrenal hyperplasia. Am J Med Genet 1989; 34:406.
  67. Woelfle J, Hoepffner W, Sippell WG, et al. Complete virilization in congenital adrenal hyperplasia: clinical course, medical management and disease-related complications. Clin Endocrinol (Oxf) 2002; 56:231.
  68. Reiner WG, Kropp BP. A 7-year experience of genetic males with severe phallic inadequacy assigned female. J Urol 2004; 172:2395.
  69. Reiner WG, Gearhart JP. Discordant sexual identity in some genetic males with cloacal exstrophy assigned to female sex at birth. N Engl J Med 2004; 350:333.
  70. Meyer-Bahlburg HF. Gender identity outcome in female-raised 46,XY persons with penile agenesis, cloacal exstrophy of the bladder, or penile ablation. Arch Sex Behav 2005; 34:423.
  71. Pasterski V, Acerini CL, Dunger DB, et al. Postnatal penile growth concurrent with mini-puberty predicts later sex-typed play behavior: Evidence for neurobehavioral effects of the postnatal androgen surge in typically developing boys. Horm Behav 2015; 69:98.
  72. De Castro R, Rondon A, Barroso U Jr, et al. Phalloplasty and urethroplasty in a boy with penile agenesis. J Pediatr Urol 2013; 9:108.e1.
  73. Garaffa G, Spilotros M, Christopher NA, Ralph DJ. Total phallic reconstruction using radial artery based forearm free flap phalloplasty in patients with epispadias-exstrophy complex. J Urol 2014; 192:814.
  74. Liao LM, Tacconelli E, Wood D, et al. Adolescent girls with disorders of sex development: A needs analysis of transitional care. J Pediatr Urol 2010; 6:609.
  75. Looijenga LH, Hersmus R, Oosterhuis JW, et al. Tumor risk in disorders of sex development (DSD). Best Pract Res Clin Endocrinol Metab 2007; 21:480.
  76. Hersmus R, de Leeuw BH, Wolffenbuttel KP, et al. New insights into type II germ cell tumor pathogenesis based on studies of patients with various forms of disorders of sex development (DSD). Mol Cell Endocrinol 2008; 291:1.
  77. Gourlay WA, Johnson HW, Pantzar JT, et al. Gonadal tumors in disorders of sexual differentiation. Urology 1994; 43:537.
  78. Verp MS, Simpson JL. Abnormal sexual differentiation and neoplasia. Cancer Genet Cytogenet 1987; 25:191.
  79. Manuel M, Katayama PK, Jones HW Jr. The age of occurrence of gonadal tumors in intersex patients with a Y chromosome. Am J Obstet Gynecol 1976; 124:293.
  80. Claahsen-van der Grinten HL, Sweep FC, Blickman JG, et al. Prevalence of testicular adrenal rest tumours in male children with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Eur J Endocrinol 2007; 157:339.
  81. Vukina J, Chism DD, Sharpless JL, et al. Metachronous Bilateral Testicular Leydig-Like Tumors Leading to the Diagnosis of Congenital Adrenal Hyperplasia (Adrenogenital Syndrome). Case Rep Pathol 2015; 2015:459318.
  82. García-Mayor RV, Sopeña B, Fluiters E, et al. Testicular adrenal-like tissue in a patient with 17 alpha-hydroxylase deficiency. Horm Res 1992; 38:241.
  83. Walker BR, Skoog SJ, Winslow BH, et al. Testis sparing surgery for steroid unresponsive testicular tumors of the adrenogenital syndrome. J Urol 1997; 157:1460.