gonadal dysgenesis

Summary

Summary: A number of syndromes with defective gonadal developments such as streak GONADS and dysgenetic testes or ovaries. The spectrum of gonadal and sexual abnormalities is reflected in their varied sex chromosome (SEX CHROMOSOMES) constitution as shown by the karyotypes of 45,X monosomy (TURNER SYNDROME); 46,XX (GONADAL DYSGENESIS, 46XX); 46,XY (GONADAL DYSGENESIS, 46,XY); and sex chromosome MOSAICISM; (GONADAL DYSGENESIS, MIXED). Their phenotypes range from female, through ambiguous, to male. This concept includes gonadal agenesis.

Top Publications

  1. Thorup J, McLachlan R, Cortes D, Nation T, Balic A, Southwell B, et al. What is new in cryptorchidism and hypospadias--a critical review on the testicular dysgenesis hypothesis. J Pediatr Surg. 2010;45:2074-86 pubmed publisher
  2. Mahood I, Scott H, Brown R, Hallmark N, Walker M, Sharpe R. In utero exposure to di(n-butyl) phthalate and testicular dysgenesis: comparison of fetal and adult end points and their dose sensitivity. Environ Health Perspect. 2007;115 Suppl 1:55-61 pubmed publisher
    ..Humans are widely exposed to DBP, but at much lower levels than those causing adverse effects in rats...
  3. Scott H, Hutchison G, Mahood I, Hallmark N, Welsh M, De Gendt K, et al. Role of androgens in fetal testis development and dysgenesis. Endocrinology. 2007;148:2027-36 pubmed
    ..Therefore, induction of MNG and Leydig cell aggregation might result from DBP-induced effects other than suppression of ITT levels...
  4. Beaulieu Bergeron M, Brochu P, Lemyre E, Lemieux N. Correlation of intercentromeric distance, mosaicism, and sexual phenotype: molecular localization of breakpoints in isodicentric Y chromosomes. Am J Med Genet A. 2011;155A:2705-12 pubmed publisher
    ..We also demonstrate that patients with an intercentromeric distance greater than 20 Mb on their idic(Y) are at increased risk of having a female sexual phenotype...
  5. Ben Temime R, Chachial A, Attial L, Ghodbanel I, Makhloufl T, Koubaal A, et al. 46 XY pure gonadal dysgenesis with gonadoblastoma and dysgerminoma. Tunis Med. 2008;86:710-3 pubmed
    Swyer syndrome is a distinct type of pure gonadal dysgenesis characterized by a 46 XY karyotype in female phenotypic patients. It shows an abnormality in testicular differentiation. It is usually revealed by primary amenorrhea...
  6. Assumpção J, Benedetti C, Maciel Guerra A, Guerra G, Baptista M, Scolfaro M, et al. Novel mutations affecting SRY DNA-binding activity: the HMG box N65H associated with 46,XY pure gonadal dysgenesis and the familial non-HMG box R30I associated with variable phenotypes. J Mol Med (Berl). 2002;80:782-90 pubmed
    ..missense mutations in the SRY gene after the screening of 17 patients, including 3 siblings, with 46,XY gonadal dysgenesis and 4 true hermaphrodites...
  7. Canto P, Vilchis F, Soderlund D, Reyes E, Mendez J. A heterozygous mutation in the desert hedgehog gene in patients with mixed gonadal dysgenesis. Mol Hum Reprod. 2005;11:833-6 pubmed
    Aetiology of mixed gonadal dysgenesis (MGD) has not been completely elucidated...
  8. Soardi F, Coeli F, Maciel Guerra A, Guerra Junior G, Mello M. Complete XY gonadal dysgenesis due to p.D293N homozygous mutation in the NR5A1 gene: a case study. J Appl Genet. 2010;51:223-4 pubmed
    ..However, only 15-20% of the cases of XY gonadal dysgenesis are due to mutations in its sequence...
  9. Ogata T, Kosho T, Wakui K, Fukushima Y, Yoshimoto M, Miharu N. Short stature homeobox-containing gene duplication on the der(X) chromosome in a female with 45,X/46,X, der(X), gonadal dysgenesis, and tall stature. J Clin Endocrinol Metab. 2000;85:2927-30 pubmed
    ..She was confirmed to have complete gonadal dysgenesis at 19 yr of age and was placed on hormone replacement therapy...

More Information

Publications62

  1. Alvarez Nava F, Soto M, Borjas L, Ortiz R, Rojas A, Martinez S, et al. Molecular analysis of SRY gene in patients with mixed gonadal dysgenesis. Ann Genet. 2001;44:155-9 pubmed
    Mixed gonadal dysgenesis (MGD) includes a group of heterogeneous conditions consisting of a dysgenetic testis with a streak gonad. MGD is probably due to a disturbance in testicular determination/differentiation...
  2. Fernandez R, Pasaro E. Tall stature and gonadal dysgenesis in a non-mosaic girl 45,X. Horm Res Paediatr. 2010;73:210-4 pubmed publisher
    ..45,X karyotype, who has a stature of 170 cm without GH treatment, and whose only apparent Turner feature is gonadal dysgenesis. The only possible explanation for the absence of Turner phenotype is the hidden mosaicism combined with an ..
  3. Macleod D, Sharpe R, Welsh M, Fisken M, Scott H, Hutchison G, et al. Androgen action in the masculinization programming window and development of male reproductive organs. Int J Androl. 2010;33:279-87 pubmed publisher
    ..controls. In conclusion, we show that the size of all male reproductive organs is programmed by androgen exposure in the MPW, but that growth towards this size is dependent on androgen action postnatally...
  4. Ting T, Chang S. Coexistence of gonadal dysgenesis and Mullerian agenesis with two mosaic cell lines 45,X/46,X,del(X)(p22.2). Zhonghua Yi Xue Za Zhi (Taipei). 2002;65:450-2 pubmed
    b>Gonadal dysgenesis and Mullerian agenesis both are common causes of primary amenorrhea. Coexistence of gonadal dysgenesis and Mullerian agenesis has been previously described as a rare event...
  5. Marrakchi A, Gharbi M, Kadiri A. [Gonadal dysgenesis associated with Mayer-Rokitansky-Küster-Hauser syndrome: a case report]. Ann Endocrinol (Paris). 2004;65:466-8 pubmed
    b>Gonadal dysgenesis with female phenotype is defined as the absence or insufficient development of the ovaries. Hypogonadism or impuberism are variable, depending on the degree of gonadal development...
  6. Jørgensen N, Rajpert De Meyts E, Main K, Skakkebaek N. Testicular dysgenesis syndrome comprises some but not all cases of hypospadias and impaired spermatogenesis. Int J Androl. 2010;33:298-303 pubmed publisher
  7. Aydos S, Tukun A, Bokesoy I. Gonadal dysgenesis and the Mayer-Rokitansky-Kuster-Hauser syndrome in a girl with 46,X,del(X)(pter-->q22:). Arch Gynecol Obstet. 2003;267:173-4 pubmed
    The association of mullerien duct with gonadal dysgenesis is extremely rare. We report such a case in a 19 year-old white woman with a 46,X,del(X)(pter-->q22:) karyotype.
  8. Sharpe R. Pathways of endocrine disruption during male sexual differentiation and masculinization. Best Pract Res Clin Endocrinol Metab. 2006;20:91-110 pubmed
    ..There is currently no definitive evidence that exposure of humans to environmental chemicals can induce testicular dysgenesis and/or impair masculinization, though pathways via which this could potentially occur are established...
  9. Rajpert De Meyts E. Developmental model for the pathogenesis of testicular carcinoma in situ: genetic and environmental aspects. Hum Reprod Update. 2006;12:303-23 pubmed
    ..The aetiology of TDS including testicular cancer remains to be elucidated, but epidemiological trends suggest a primary role for environmental factors, probably combined with genetic susceptibility...
  10. Han T, Goswami D, Trikudanathan S, Creighton S, Conway G. Comparison of bone mineral density and body proportions between women with complete androgen insensitivity syndrome and women with gonadal dysgenesis. Eur J Endocrinol. 2008;159:179-85 pubmed publisher
    To compare bone mineral density (BMD) and body proportions between women with complete androgen insensitivity syndrome (CAIS) and with gonadal dysgenesis (GD).
  11. Amice V, Amice J, Bercovici J, Riviere D, Corolleur M. Gonadal tumor and H-Y antigen in 46,XY pure gonadal dysgenesis. Cancer. 1986;57:1313-7 pubmed
    Six cases of Swyer's syndrome (46,XY pure gonadal dysgenesis) are reported. Three patients, without gonadal tumor, had female H-Y antigen. Three patients, after gonadal tumor ablation, had intermediate H-Y antigen levels...
  12. Cetinkaya E, Ocal G, Berberoglu M, Adiyaman P, Ekim M, Yalcinkaya F, et al. Association of partial gonadal dysgenesis, nephropathy and WT1 gene mutation without Wilms' tumor: incomplete Denys-Drash syndrome. J Pediatr Endocrinol Metab. 2001;14:561-4 pubmed
    ..We report an infant with male pseudohermaphroditism due to partial gonadal dysgenesis and nephropathy without Wilms' tumor but with a Wilms' tumor suppressor gene (WT1) mutation...
  13. Muller J, Ritzen E, Ivarsson S, Rajpert De Meyts E, Norjavaara E, Skakkebaek N. Management of males with 45,X/46,XY gonadal dysgenesis. Horm Res. 1999;52:11-4 pubmed
    ..On the basis of our current knowledge we propose a strategy for management and follow-up of these boys in order to detect possible premalignant histological changes early and prevent development of a gonadal tumour...
  14. Bakoto N, Corman V, Legros J. Ascending aortic aneurysm in a patient with mixed gonadal dysgenesis. Ann Endocrinol (Paris). 2011;72:45-7 pubmed publisher
    ..This case report, and the few others, which have been previously reported in the literature, emphasizes the importance of cardiologic and endocrine follow-up in male carriers of 45,X/46,XY mosaicism...
  15. Finelli P, Pincelli A, Russo S, Bonati M, Recalcati M, Masciadri M, et al. Disruption of friend of GATA 2 gene (FOG-2) by a de novo t(8;10) chromosomal translocation is associated with heart defects and gonadal dysgenesis. Clin Genet. 2007;71:195-204 pubmed
    ..1;q21.1) translocation who was born with congenital secundum-type atrial septal defect and gonadal dysgenesis. Fluorescence in situ hybridization mapped the chromosome 8 translocation breakpoint (bkp) to within the ..
  16. Umehara F, Tate G, Itoh K, Yamaguchi N, Douchi T, Mitsuya T, et al. A novel mutation of desert hedgehog in a patient with 46,XY partial gonadal dysgenesis accompanied by minifascicular neuropathy. Am J Hum Genet. 2000;67:1302-5 pubmed
    We describe a patient with 46,XY partial gonadal dysgenesis (PGD) who presented with polyneuropathy...
  17. Bazin C, Denis B, Capy P, Bonnivard E, Higuet D. Characterization of permissivity for hobo-mediated gonadal dysgenesis in Drosophila melanogaster. Mol Gen Genet. 1999;261:480-6 pubmed
    ..Moreover, permissivity decreases with age in E females. Our results are discussed with respect to similar phenomena that have been described in relation to the reactivity of the IR dysgenic system...
  18. Domenice S, Yumie Nishi M, Correia Billerbeck A, Latronico A, Aparecida Medeiros M, Russell A, et al. A novel missense mutation (S18N) in the 5' non-HMG box region of the SRY gene in a patient with partial gonadal dysgenesis and his normal male relatives. Hum Genet. 1998;102:213-5 pubmed
    ..region of the Y chromosome (the SRY gene) have been reported in low frequency in patients with 46,XY gonadal dysgenesis. We investigated 21 Brazilian 46,XY sex-reversed patients, who presented either complete or partial gonadal ..
  19. Dalgaard M, Weinhold N, Edsgard D, Silver J, Pers T, Nielsen J, et al. A genome-wide association study of men with symptoms of testicular dysgenesis syndrome and its network biology interpretation. J Med Genet. 2012;49:58-65 pubmed publisher
    ..The incidence of these disorders has increased over the last few decades, and testicular cancer now affects 1% of the Danish and Norwegian male population...
  20. Goldberg M, Yassir W, Sadeghi Nejad A, Stanitski C. Clinical analysis of short stature. J Pediatr Orthop. 2002;22:690-6 pubmed
  21. Joensen U, Jørgensen N, Skakkebaek N. Testicular dysgenesis syndrome and carcinoma in situ of the testes. Nat Clin Pract Urol. 2007;4:402-3 pubmed
  22. Akre O, Richiardi L. Does a testicular dysgenesis syndrome exist?. Hum Reprod. 2009;24:2053-60 pubmed publisher
    ..There is furthermore little evidence of shared causes between the alleged components of the syndrome...
  23. Delattre M, Anxolabehere D, Coen D. Prevalence of localized rearrangements vs. transpositions among events induced by Drosophila P element transposase on a P transgene. Genetics. 1995;141:1407-24 pubmed
    ..We propose that the P transposase induces mainly localized events. Some of these could result from frequent changes of template during gap-repair DNA synthesis, and/or from abortive transposition...
  24. Capito C, Arnaud A, Hameury F, Frémond B, Lardy H, Leclair M, et al. Dysgerminoma and gonadal dysgenesis: the need for a new diagnosis tree for suspected ovarian tumours. J Pediatr Urol. 2011;7:367-72 pubmed publisher
    ..in the paediatric age group is uncommon, and most cases arise from dysgenetic gonads of 46, XY pure gonadal dysgenesis (PGD) patients. Bilateral gonadectomy is mandatory in these patients...
  25. Kokcu A, Tosun M, Cetinkaya M, Bildircin D, Celik H. Pure gonadal dysgenesis and spontaneous pregnancy: a case report. Gynecol Endocrinol. 2010;26:103-4 pubmed publisher
    We report a case of pure gonadal dysgenesis with streak gonads in which spontaneous conception occurred 10 years after the diagnosis. Her pregnancy proceeded as normal, and she gave birth to a live baby at term by cesarean section...
  26. Giwercman A, Giwercman Y. Environmental factors and testicular function. Best Pract Res Clin Endocrinol Metab. 2011;25:391-402 pubmed publisher
  27. Harley V. The molecular action of testis-determining factors SRY and SOX9. Novartis Found Symp. 2002;244:57-66; discussion 66-7, 79-85, 253-7 pubmed
    ..being the only region conserved between species and the site of almost all clinical mutations causing XY gonadal dysgenesis. By contrast, SOX9 harbours a number of highly conserved regions, including two domains required for maximal ..
  28. Warman D, Costanzo M, Marino R, Berensztein E, Galeano J, Ramirez P, et al. Three new SF-1 (NR5A1) gene mutations in two unrelated families with multiple affected members: within-family variability in 46,XY subjects and low ovarian reserve in fertile 46,XX subjects. Horm Res Paediatr. 2011;75:70-7 pubmed publisher
    ..Three novel heterozygous SF-1 gene mutations affecting multiple members of two unrelated families with a history of 46,XY disorders of sex development (DSD) and 46,XX ovarian insufficiency are described...
  29. Mondal S, Guha D, Banerjee D, Sinha S. Study of primary amenorrhoea with special reference to cytogenetic evaluation. Indian J Pathol Microbiol. 2002;45:155-9 pubmed
    ..55%), systemic disease like Tuberculosis and Idiopathic 2 cases (2.77%) each. Chromosomal aberration was seen in 24 cases (33.33%) and it comes second most common cause of primary amenorrhoea after mullerian duct abnormalities...
  30. Modi D, Sane S, Bhartiya D. Over-expression of Müllerian inhibiting substance mRNA in the Turner syndrome ovary. Sex Dev. 2009;3:245-52 pubmed publisher
    ..or partial loss of one of the X chromosomes, varying degrees of multiple congenital malformations and gonadal dysgenesis. However, the reason for the premature loss of germ cells in the TS ovaries is currently unknown...
  31. Rocha V, Guerra Junior G, Marques de Faria A, de Mello M, Maciel Guerra A. Complete gonadal dysgenesis in clinical practice: the 46,XY karyotype accounts for more than one third of cases. Fertil Steril. 2011;96:1431-4 pubmed publisher
    To determine the frequency of XY karyotypes among females with complete gonadal dysgenesis (CGD) and to investigate the frequency of both gonadal tumors and SRY mutations.
  32. Chakrabarti S, Marshall I. Another unusual presentation of McCune Albright syndrome with fibrous dysplasia, unilateral testicular enlargement, and testicular microlithiasis. J Pediatr Endocrinol Metab. 2010;23:513-5 pubmed
    ..This is the first report of a patient with an atypical form of MAS presenting with unilateral testicular enlargement not associated with sexual precocity, and with testicular microlithiasis...
  33. van den Driesche S, Kolovos P, Platts S, Drake A, Sharpe R. Inter-relationship between testicular dysgenesis and Leydig cell function in the masculinization programming window in the rat. PLoS ONE. 2012;7:e30111 pubmed publisher
    ..The findings provide strong validation of the TDS hypothesis...
  34. Bouma G, Affourtit J, Bult C, Eicher E. Transcriptional profile of mouse pre-granulosa and Sertoli cells isolated from early-differentiated fetal gonads. Gene Expr Patterns. 2007;7:113-23 pubmed
    ..Among the newly identified differentially expressed transcripts are potential GSD genes involved in unexplained human sex reversal cases...
  35. Morerio C, Calvari V, Rosanda C, Porta S, Gambini C, Panarello C. XY female with a dysgerminoma and no mutation in the coding sequence of the SRY gene. Cancer Genet Cytogenet. 2002;136:58-61 pubmed
    We report a 46,XY 11-year-old girl with pure gonadal dysgenesis who developed a dysgerminoma...
  36. Sultan C, Lumbroso S, Paris F, Jeandel C, Terouanne B, Belon C, et al. Disorders of androgen action. Semin Reprod Med. 2002;20:217-28 pubmed
    ..Psychological follow-up is necessary...
  37. Rajpert De Meyts E, Hanstein R, Jørgensen N, Graem N, Vogt P, Skakkebaek N. Developmental expression of POU5F1 (OCT-3/4) in normal and dysgenetic human gonads. Hum Reprod. 2004;19:1338-44 pubmed
  38. Connolly G, Devaney D, McKenna P. A case of cervical dysgenesis. J Obstet Gynaecol. 2004;24:322-3 pubmed
  39. Jaubert F, Nihoul Fekete C, Lortat Jacob S, Josso N, Fellous M. [Hermaphroditism pathology]. Ann Pathol. 2004;24:499-509 pubmed
    ..Sexual determinism deficiencies are then presented: Turner syndrome, XX males, pure gonadal dysgenesis, true hermaphroditism, mixed gonadal dysgenesis, Drash and Frasier syndrome...
  40. Blumenstiel J, Hartl D. Evidence for maternally transmitted small interfering RNA in the repression of transposition in Drosophila virilis. Proc Natl Acad Sci U S A. 2005;102:15965-70 pubmed
    ..virilis. We also present evidence that the maternal inheritance of these endogenous siRNAs may contribute to maternal repression of Penelope...
  41. Puffenberger E, Hu Lince D, Parod J, Craig D, Dobrin S, Conway A, et al. Mapping of sudden infant death with dysgenesis of the testes syndrome (SIDDT) by a SNP genome scan and identification of TSPYL loss of function. Proc Natl Acad Sci U S A. 2004;101:11689-94 pubmed
    ..These results shed light on the pathogenesis of a disorder of sexual differentiation and brainstem-mediated sudden death, as well as give insight into a mechanism of transcriptional regulation...
  42. Else T, Hammer G. Genetic analysis of adrenal absence: agenesis and aplasia. Trends Endocrinol Metab. 2005;16:458-68 pubmed
    ..Recent advancements in the field of human and mouse genetics have accumulated evidence for a host of novel factors involved in these processes, such as the hedgehog signaling network and peptides derived from proopiomelanocortin...
  43. Skakkebaek N, Holm M, Hoei Hansen C, Jørgensen N, Rajpert De Meyts E. Association between testicular dysgenesis syndrome (TDS) and testicular neoplasia: evidence from 20 adult patients with signs of maldevelopment of the testis. APMIS. 2003;111:1-9; discussion 9-11 pubmed
    ..We speculate that most of these abnormalities are caused by adverse environmental effects rather than specific gene mutations...
  44. Bay K, Asklund C, Skakkebaek N, Andersson A. Testicular dysgenesis syndrome: possible role of endocrine disrupters. Best Pract Res Clin Endocrinol Metab. 2006;20:77-90 pubmed
    ..Clinicians should be aware of the interconnection between the different features of TDS, and inclusion of a programme for early detection of testis cancer in the management of infertile men with poor semen quality is recommended...
  45. Kumar A, Mishra S, Dogra P. Management of an unusual case of atypical Mayer-Rokitansky-Kuster-Hauser syndrome, with unilateral gonadal agenesis, solitary ectopic pelvic kidney, and pelviureteric junction obstruction. Int Urogynecol J Pelvic Floor Dysfunct. 2007;18:823-5 pubmed
    ..After doing thorough Medline search, to the best of our knowledge, this is the first case reported with this combination...
  46. Williams E, Appanna T, Foster M. Management of the impalpable testis: a six year review together with a national experience. Postgrad Med J. 2001;77:320-2 pubmed
    ..Laparoscopy for the impalpable testis is not initially warranted. An inguinal exploration is regarded as the definitive investigation. This has the advantage of providing the diagnosis and treatment in the majority of cases...
  47. Teuscher C, Wardell B, Lunceford J, Michael S, Tung K. Aod2, the locus controlling development of atrophy in neonatal thymectomy-induced autoimmune ovarian dysgenesis, co-localizes with Il2, Fgfb, and Idd3. J Exp Med. 1996;183:631-7 pubmed
    ..Most significant, however, is the co-localization of Aod2 to Idd3, a susceptibility gene that plays a role in autoimmune insulin-dependent type 1 diabetes mellitus in the nonobese diabetic mouse...
  48. Saffarini C, Heger N, Yamasaki H, Liu T, Hall S, Boekelheide K. Induction and persistence of abnormal testicular germ cells following gestational exposure to di-(n-butyl) phthalate in p53-null mice. J Androl. 2012;33:505-13 pubmed publisher
    ..This unique model identified a role for p53 in the perinatal apoptosis of DBP-induced MNGs and provided insight into the long-term effects of gestational DBP exposure within a p53-null environment...
  49. Sills E, Cotter P, Marron K, Shkrobot L, Walsh H, Salem R. Ovarian dysgenesis associated with an unbalanced X;6 translocation: first characterisation of reproductive anatomy and cytogenetic evaluation in partial trisomy 6 with breakpoints at Xq22 and 6p23. Mol Med Rep. 2012;5:29-31 pubmed publisher
    ..history and cytogenetic techniques were used to characterise a novel chromosomal anomaly associated with gonadal dysgenesis. A healthy non-dysmorphic 23 year-old phenotypic female with primary amenorrhea and infertility presented ..
  50. Yukuhiro K, Mukai T. A type of incompatibility between genes and their genetic background inducing decrease in heterozygote viability approximately equal to that of homozygotes, found in a natural population of Drosophila. Heredity (Edinb). 1993;71 ( Pt 1):74-80 pubmed
  51. Tommerup N, Schempp W, Meinecke P, Pedersen S, Bolund L, Brandt C, et al. Assignment of an autosomal sex reversal locus (SRA1) and campomelic dysplasia (CMPD1) to 17q24.3-q25.1. Nat Genet. 1993;4:170-4 pubmed
    ..The mouse mutant tail-short (Ts) which maps to the homologous syntenic region on mouse chromosome 11, displays some of the features of CMPD1...
  52. Bazin C, Lemeunier F, Periquet G, Silber J. Genetic and molecular analyses of vgal: a spontaneous and unstable mutation at the vestigial locus in Drosophila melanogaster. Genet Res. 1991;57:235-43 pubmed
    ..One is the excision of the resident hobo element, the other a further deletion (about 300 bp in the example characterized herein). The vge mutation is probably due to a deletion of vestigial sequences flanking the hobo insertion...
  53. Getz C, van Schaik N. Somatic mutation in the wings of Drosophila melanogaster females dysgenic due to P elements when reared at 29 degrees C. Mutat Res. 1991;248:187-94 pubmed
    ..This is in direct contrast to the large body of research which indicates that P-transposition-mediated mutation is restricted to the germline...