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Frauenheilkunde up2date 2016; 10(02): 139-158
DOI: 10.1055/s-0042-103871
Gynäkologische Endokrinologie und Reproduktionsmedizin
Georg Thieme Verlag KG Stuttgart · New York

Störungen/Besonderheiten der Geschlechtsentwicklung

Paul-Martin Holterhus
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Publication Date:
15 April 2016 (online)

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Kernaussagen

Bei den Störungen der Geschlechtsentwicklung/Besonderheiten der Geschlechtsentwicklung handelt es sich um seltene oder sehr seltene, komplexe Diagnosen. Obwohl phänomenologisch zunächst die besondere Genitalentwicklung im Vordergrund steht, wirken sich genetische und hormonelle Konstellation vielfältig auf extragenitale Eigenschaften betroffener Individuen aus. Zu den wichtigsten Aspekten zählen die hohe Prävalenz von bis zu 30 % assoziierter Fehlbildungen und die Mechanismen einer differenziellen hormonellen Prägung des Gehirns als Einflussfaktor des psychischen Geschlechts.

Aufgrund der vielfältigen Varianten und Verläufe vor dem Hintergrund eines jeweils hoch individuellen psychosozialen Hintergrunds kommt multidisziplinär, holistisch ausgerichteten Kompetenzzentren für DSD eine führende Rolle in der Koordination diagnostischer, beratender und ggf. therapeutischer Maßnahmen zu.

 

  • Literatur

  • 1 Hughes IA, Houk C, Ahmed SF et al. Consensus statement on management of intersex disorders. Arch Dis Child 2006; 91: 554-563
    Google Scholar
  • 2 Thyen U, Lanz K, Holterhus PM et al. Epidemiology and initial management of ambiguous genitalia at birth in Germany. Horm Res 2006; 66: 195-203
    CrossrefGoogle Scholar
  • 3 Wiesemann C, Ude-Koeller S, Sinnecker GH et al. Ethical principles and recommendations for the medical management of differences of sex development (DSD)/intersex in children and adolescents. Eur J Pediatr 2010; 169: 671-679
    CrossrefGoogle Scholar
  • 4 Sinclair AH, Berta P, Palmer MS et al. A gene from the human sex-determining region encodes a protein with homology to a conserved DNA-binding motif. Nature 1990; 346: 240-244
    CrossrefPubMedGoogle Scholar
  • 5 Ono M, Harley VR. Disorders of sex development: new genes, new concepts. Nat Rev Endocrinol 2013; 9: 79-91
    Google Scholar
  • 6 Oppelt P, Dörr H-G Hrsg. Kinder- und Jugendgynäkologie. Stuttgart: Thieme; 2014
    Google Scholar
  • 7 Bao AM, Swaab DF. Sex differences in the brain, behavior, and neuropsychiatric disorders. Neuroscientist 2010; 16: 550-565
    CrossrefGoogle Scholar
  • 8 Dewing P, Shi T, Horvath S et al. Sexually dimorphic gene expression in mouse brain precedes gonadal differentiation. Brain Res Mol Brain Res 2003; 118: 82-90
    CrossrefGoogle Scholar
  • 9 Berenbaum SA. Effects of early androgens on sex-typed activities and interests in adolescents with congenital adrenal hyperplasia. Horm Behav 1999; 35: 102-110
    CrossrefGoogle Scholar
  • 10 Meyer-Bahlburg HF, Dolezal C, Baker SW et al. Prenatal androgenization affects gender-related behavior but not gender identity in 5–12-year-old girls with congenital adrenal hyperplasia. Arch Sex Behav 2004; 33: 97-104
    CrossrefGoogle Scholar
  • 11 Jürgensen M, Hiort O, Holterhus PM et al. Gender role behavior in children with XY karyotype and disorders of sex development. Horm Behav 2007; 51: 443-453
    CrossrefGoogle Scholar
  • 12 Hines M, Ahmed SF, Hughes IA. Psychological outcomes and gender-related development in complete androgen insensitivity syndrome. Arch Sex Behav 2003; 32: 93-101
    CrossrefGoogle Scholar
  • 13 Cools M, Drop SL, Wolffenbuttel KP et al. Germ cell tumors in the intersex gonad: old paths, new directions, moving frontiers. Endocr Rev 2006; 27: 468-484
    CrossrefGoogle Scholar
  • 14 Achermann JC, Hughes IA. Disorders of Sex Development. In: Kronenberg HM, Melmed S, Polonsky KS, Larsen PR, eds. Williams Textbook of Endocrinology. Philadelphia: Saunders Elsevier; 2008: 783-848
    Google Scholar
  • 15 Achermann JC, Ito M, Ito M et al. A mutation in the gene encoding steroidogenic factor-1 causes XY sex reversal and adrenal failure in humans. Nat Genet 1999; 22: 125-126
    CrossrefGoogle Scholar
  • 16 Köhler B, Lin L, Ferraz-de-Souza B et al. Five novel mutations in steroidogenic factor 1 (SF1, NR5A1) in 46,XY patients with severe underandrogenization but without adrenal insufficiency. Hum Mutat 2008; 29: 59-64
    CrossrefGoogle Scholar
  • 17 Holterhus PM, Hiort O. Störung der Pubertätsentwicklung. In: Lehnert H, Hrsg. Rationelle Diagnostik und Therapie in Endokrinologie, Diabetologie und Stoffwechsel. Stuttgart: Thieme; 2015
    Google Scholar
  • 18 Hiort O, Holterhus PM, Werner R et al. Homozygous disruption of P450 side-chain cleavage (CYP11A1) is associated with prematurity, complete 46,XY sex reversal, and severe adrenal failure. J Clin Endocrinol Metab 2005; 90: 538-541
    CrossrefGoogle Scholar
  • 19 Welzel M, Wüstemann N, Simic-Schleicher G et al. Carboxyl-terminal mutations in 3beta-hydroxysteroid dehydrogenase type II cause severe salt-wasting congenital adrenal hyperplasia. J Clin Endocrinol Metab 2008; 93: 1418-1425
    CrossrefGoogle Scholar
  • 20 Flück CE, Tajima T, Pandey AV et al. Mutant P450 oxidoreductase causes disordered steroidogenesis with and without Antley-Bixler syndrome. Nat Genet 2004; 36: 228-230
    CrossrefGoogle Scholar
  • 21 Richter-Unruh A, Martens JW, Verhoef-Post M et al. Leydig cell hypoplasia: cases with new mutations, new polymorphisms and cases without mutations in the luteinizing hormone receptor gene. Clin Endocrinol 2002; 56: 103-112
    CrossrefGoogle Scholar
  • 22 Twesten W, Holterhus P, Sippell WG et al. Clinical, endocrine, and molecular genetic findings in patients with 17beta-hydroxysteroid dehydrogenase deficiency. Horm Res 2000; 53: 26-31
    CrossrefGoogle Scholar
  • 23 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: 399-410
    CrossrefGoogle Scholar
  • 24 Sinnecker GH, Hiort O, Dibbelt L et al. Phenotypic classification of male pseudohermaphroditism due to steroid 5 alpha-reductase 2 deficiency. Am J Med Genet 1996; 63: 223-230
    CrossrefGoogle Scholar
  • 25 Hiort O, Holterhus PM. The molecular basis of male sexual differentiation. Eur J Endocrinol 2000; 142: 101-110
    CrossrefGoogle Scholar
  • 26 Quigley CA, De Bellis A, Marschke KB et al. Androgen receptor defects: historical, clinical, and molecular perspectives. Endocr Rev 1995; 16: 271-321
    CrossrefGoogle Scholar
  • 27 Hannema SE, Scott IS, Hodapp J et al. Residual activity of mutant androgen receptors explains wolffian duct development in the complete androgen insensitivity syndrome. J Clin Endocrinol Metab 2004; 89: 5815-5822
    CrossrefGoogle Scholar
  • 28 Sinnecker GH, Hiort O, Nitsche EM et al. Functional assessment and clinical classification of androgen sensitivity in patients with mutations of the androgen receptor gene. German Collaborative Intersex Study Group. Eur J Pediatr 1997; 156: 7-14
    CrossrefGoogle Scholar
  • 29 Hiort O, Sinnecker GH, Holterhus PM et al. Inherited and de novo androgen receptor gene mutations: investigation of single-case families. J Pediatr 1998; 132: 939-943
    CrossrefGoogle Scholar
  • 30 Holterhus PM, Wiebel J, Sinnecker GH et al. Clinical and molecular spectrum of somatic mosaicism in androgen insensitivity syndrome. Pediatr Res 1999; 46: 684-690
    CrossrefGoogle Scholar
  • 31 Holterhus PM, Werner R, Hoppe U et al. Molecular features and clinical phenotypes in androgen insensitivity syndrome in the absence and presence of androgen receptor gene mutations. J Mol Med 2005; 83: 1005-1013
    CrossrefGoogle Scholar
  • 32 Adachi M, Takayanagi R, Tomura A et al. Androgen-insensitivity syndrome as a possible coactivator disease. N Engl J Med 2000; 343: 856-862
    CrossrefGoogle Scholar
  • 33 Appari M, Werner R, Wünsch L et al. Apolipoprotein D (APOD) is a putative biomarker of androgen receptor function in androgen insensitivity syndrome. J Mol Med 2009; 87: 623-632
    CrossrefGoogle Scholar
  • 34 Holterhus PM, Köhler B, Korsch E, Richter-Unruh A. im Auftrag der Arbeitsgemeinschaft Pädiatrische Endokrinologie (APE) der Deutschen Gesellschaft für Kinderheilkunde und Jugendmedizin (DGKJ) und der Deutschen Gesellschaft für Endokrinologie (DGE). S1-Leitlinie Störungen der Geschlechtsentwicklung. AWMF, Erstellungsdatum 10/2007, letzte Überarbeitung 10/2010. Im Internet: http://www.awmf.org Stand: 08.03.2014
    Google Scholar
  • 35 Wünsch L, Holterhus PM, Wessel L et al. 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-E965
    CrossrefGoogle Scholar
  • 36 Mendez JP, Schiavon R, Diaz-Cueto L et al. A reliable endocrine test with human menopausal gonadotropins for diagnosis of true hermaphroditism in early infancy. J Clin Endocrinol Metab 1998; 83: 3523-3526
    Google Scholar
  • 37 Kubini K, Zachmann M, Albers N et al. Basal inhibin B and the testosterone response to human chorionic gonadotropin correlate in prepubertal boys. J Clin Endocrinol Metab 2000; 85: 134-138
    CrossrefGoogle Scholar
  • 38 Rey RA, Belville C, Nihoul-Fékété C et al. Evaluation of gonadal function in 107 intersex patients by means of serum antimüllerian hormone measurement. J Clin Endocrinol Metab 1999; 84: 627-631
    CrossrefPubMedGoogle Scholar
  • 39 Kulle AE, Riepe FG, Melchior D et al. A novel ultrapressure liquid chromatography tandem mass spectrometry method for the simultaneous determination of androstenedione, testosterone, and dihydrotestosterone in pediatric blood samples: age- and sex-specific reference data. J Clin Endocrinol Metab 2010; 95: 2399-2409
    CrossrefPubMedGoogle Scholar
  • 40 Kulle AE, Welzel M, Holterhus PM et al. Implementation of a liquid chromatography tandem mass spectrometry assay for eight adrenal C-21 steroids and pediatric reference data. Horm Res Paediatr 2013; 16: 22-31
    Google Scholar
  • 41 Krone N, Reisch N, Idkowiak J et al. Genotype-phenotype analysis in congenital adrenal hyperplasia due to P450 oxidoreductase deficiency. J Clin Endocrinol Metab 2012; 97: E257-E267
    CrossrefGoogle Scholar
  • 42 Gillam LH, Hewitt JK, Warne GL. Ethical principles for the management of infants with disorders of sex development. Horm Res Paediatr 2010; 74: 412-418
    CrossrefGoogle Scholar
  • 43 Deutscher Ethikrat. Intersexualität (2013). Im Internet: http://www.ethikrat.org/intersexualitaet Stand: 08.03.2014
    Google Scholar