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Gonadal Dysgenesis

Gonadal dysgenesis is the failure of typical sexual development due to chromosomal and developmental errors. It usually affects the reproductive system as well as the urinary system and encompasses a range of phenotypes.


Affected individuals may have a family history of genetic sexual conditions or infertility. A prenatal history may also reveal maternal increased exposure to androgens. On physical examination findings may be ambiguous or seemingly normal genitalia [1]. Gonads may or may not be palpable. Gonadal dysgenesis (GD) may result in genitalia that is discordant with the genotype, in addition to the presence of streak gonads. Presentation of GD may occur during childhood, adolescence, or at an even later stage, with complaints such as amenorrhea, lack of pubertal development, and infertility.

One type of GD entails disorders that are genetic and are perpetuated by abnormal chromosomes, examples of which are Turner's syndrome and Klinefelter syndrome [2]. These can have variable karyotypes.

Disorders of sex development can either be 46,XX or 46,XY. They take place due to a disruption in the pathways necessary for gonadal and urogenital development. In 46,XY disorders, patients are genotypically male but may have ambiguous genitalia (seen in partial GD) or completely female genitalia (seen in complete GD).

Presentation of those with 46,XX may be that of a phenotypic male, or they may have normal female genitalia but in both cases lack functional ovaries [3]. They may present with primary amenorrhea. Moreover, concomitant renal and lung dysfunction may be found. Anomalies in sexual development arise due to errors in the expression of certain genes, such as R-spondin-1 (RSPO1) or sex-determining region Y (SRY), which may predispose patients to other conditions such as squamous cell carcinoma or excess androgens in utero.

The most commonly reported form of GD is congenital adrenal hypoplasia (CAH) and is often seen after overexposure to external androgens prenatally.

  • The incidence of osteopenia changed from 69.70% to 22.22% and that of osteoporosis changed from 18.18% to 0. Dysgeminoma was found in one patient.[ncbi.nlm.nih.gov]
  • Hormone replacement therapy also helps reduce the risk of reduced bone density (osteopenia and osteoporosis ). Women with this disorder do not produce eggs (ova), but they may be able to become pregnant with a donated egg or embryo.[ghr.nlm.nih.gov]
  • Patients also manifested a unique syndrome of extragonadal anomalies, including typical facial gestalt, low birth weight, myopathy, rod and cone dystrophy, anal atresia, omphalocele, sensorineural hearing loss, dry and scaly skin, skeletal abnormalities[ncbi.nlm.nih.gov]
Visual Hallucination
  • We present a 27-yr-old female with gonadal dysgenesis (46, XY), who presented to our hospital with poor consciousness, aphasia, restlessness, and visual hallucination.[ncbi.nlm.nih.gov]
  • We present a 27-yr-old female with gonadal dysgenesis (46, XY), who presented to our hospital with poor consciousness, aphasia, restlessness, and visual hallucination.[ncbi.nlm.nih.gov]
  • The condition usually becomes apparent first in adolescence with delayed puberty and primary amenorrhea. Herein the authors present the case of a 27-year-old woman with primary amenorrhea and undeveloped breasts.[ncbi.nlm.nih.gov]
  • It usually first becomes apparent in adolescence with delayed puberty and amenorrhea. Rarely, patients can present with spontaneous breast development and/or menstruation.[ncbi.nlm.nih.gov]
  • Two sisters with a main complaint of primary amenorrhea and another case, their mother's maternal aunt with the same history of primary amenorrhea but married with no consanguinity and no children. None.[ncbi.nlm.nih.gov]
  • To determine the genetic cause of primary amenorrhea in a 46,XY adolescent girl. Case report. Pediatric endocrinology and gynecologic unit of an academic hospital. A 16-year-old adolescent referred for primary amenorrhea.[ncbi.nlm.nih.gov]
  • Patients usually presents with primary amenorrhea with underdeveloped secondary sex characteristics. Phenotypes of these patients are female.[ncbi.nlm.nih.gov]


A family history and prenatal history are useful in determining whether or not there is a genetic cause, and in exposing the influence of external androgens on the fetus.

As there is a vast differential for gonadal dysgenesis, tests carried out are to narrow down the possible diagnosis. Despite this, there are some cases where a diagnosis is never reached [1] [4]. Genetic testing and karyotyping may be conducted to determine the genotype of the individual, although it is not routinely performed. Hormonal tests are also done to assess the functionality of gonads and adrenal glands, as CAH is a common GD. Hormonal stimulation tests are utilized in the determination of receptor abnormalities. Urinalysis is also indicated.

The first imaging study done is usually a pelvic ultrasound. This gives information on the internal urogenital structures. Genitograms performed with contrast provide further information on the ductal system of the pelvic organs. Computerized tomography (CT) and magnetic resonance imaging (MRI) are not routinely used.

Individuals for whom all other modalities fail to establish a clear result, surgical exploration via laparoscopy or laparotomy is possible, although laparoscopy is often preferred [4] [5]. A biopsy of tissue determines its origin and may aid in making a final diagnosis [6].

Brain Edema
  • Computed tomography scan of the head and neck revealed the presence of brain edema, hydrocephalous, and a localized hypodense lesion in the hypothalamus.[ncbi.nlm.nih.gov]


  • The patient had pure 46,XY gonadal dysgenesis with hypoplastic uterus, estrogen treatment for amenorrhea, and no neoplastic changes on the histopathology report.[ncbi.nlm.nih.gov]
  • Although growth hormone (GH) treatment has been suggested to treat growth impairment, conflicting data surround this issue.[ncbi.nlm.nih.gov]
  • After 2 years of treatment, all patients had obvious breast development; the uterus showed (2.38   0.60)   (1.38   0.70)   (1.38   0.55) cm growth.[ncbi.nlm.nih.gov]
  • The treatment and the follow up are detailed. CONCLUSION: The presence of Y chromosome in the karyotype of a patient presenting a gonadal dysgenesis must lead to prophylactic bilateral gonadectomy in order to avoid a malignant transformation.[ncbi.nlm.nih.gov]
  • Because of an increased risk of gonadoblastoma, proper early diagnosis and treatment prevent development of malignancies.[ncbi.nlm.nih.gov]


  • […] gonadal dysgenesis (CGD) / Swyer syndrome mixed gonadal dysgenesis (MGD) pure gonadal dysgenesis (PGD) Associations syndromic associations Turner syndrome ( streak ovaries ) DRASH syndrome other associations Madelung deformity gonadoblastoma Treatment and prognosis[radiopaedia.org]
  • Prognosis With appropriate management, the physiological and clinical outcome for patients is good. The documents contained in this web site are presented for information purposes only.[orpha.net]
  • Prognosis With appropriate management, the risk of malignancy is low and the psychological and clinical outcome for patients is good. The documents contained in this web site are presented for information purposes only.[orpha.net]
  • Hum Reprod 11 (Suppl 4):1–26 PubMed Google Scholar Vermeulen A, Vandeweghe M, Deslypere JP (1986) Prognosis of subfertility in men with corrected or uncorrected varicocele.[doi.org]


  • However, its exact etiological role in gonadal dysgenesis in patients with Y chromosome mosaicisms has not yet been clarified.[ncbi.nlm.nih.gov]
  • Mutation of the Wilms tumor suppressor gene (WT1) has been recognized as one of the etiologies of steroid-resistant nephrotic syndrome (SRNS). The mutation is also responsible for gonadal dysgenesis in 46,XY individuals.[ncbi.nlm.nih.gov]
  • The molecular etiology is not known in about 2 thirds of instances. The aim of this study was to identify the genetic cause in patients with 46,XY gonadal dysgenesis.[ncbi.nlm.nih.gov]
  • The etiology of several cases of XY gonadal dysgenesis remains unknown, but X/XY gonadal mosaicism has been hypothesized to play a role.[ncbi.nlm.nih.gov]
  • Etiology Ovarian dysgenesis results from genetic defects of ovarian development.[orpha.net]


  • Its epidemiology in Sub-Saharan Africa is not known. This study reports experience in the management of 3 cases at the Yaounde Gynecologic-Obstetric and Paediatric Hospital.[ncbi.nlm.nih.gov]
  • Summary Epidemiology Prevalence is unknown but is thought to be less than 1/10,000. Clinical description Patients are born as females without ambiguity.[orpha.net]
  • Summary Epidemiology The prevalence is unknown. Clinical description Patients present during adolescence or early adulthood with normal female external genitalia but lack pubertal development although adrenarche is normal.[orpha.net]
  • J Urol 124:757–767 PubMed Google Scholar Garner MJ, Turner MC, Ghadirian P, Krewski D (2005) Epidemiology of testicular cancer: an overview.[doi.org]
Sex distribution
Age distribution


  • PPPR3C provides insight into pathophysiology, as well as emerging as a potential therapeutic target for male infertility.[ncbi.nlm.nih.gov]
  • Pathophysiology and clinical assessment of primary amenorrhea. Frontiers in Gynecological Endocrinology. New York: Springer; 2014. p. 3-7. 3. Speroff L, Fritz MA. Clinical gynecologic endocrinology and infertility.[advbiores.net]
  • Molecular genetics and pathophysiology of 17 beta-hydroxysteroid dehydrogenase 3 deficiency. J Clin Endocrinol Metab. 1996;81:130–6. PubMed Google Scholar Rosler A, Bélanger A, Labrie F.[doi.org]
  • Currently, the basic pathophysiology of the lack of androgen effect on the genitalia is understood more fully. Some patients are receptor-negative; their cytosol receptors cannot bind DHT.[emedicine.medscape.com]
  • J Ped Endocrinol Metab 19:499–505 Google Scholar Simoni M, Gromoll J, Nieschlag E (1997) The follicle-stimulating hormone receptor: biochemistry, molecular biology, physiology, and pathophysiology.[doi.org]


  • Once the diagnosis of Swyer syndrome is established, early treatment is crucial to prevent the development of gonadal malignancy and to enable a normal sex life, and even carry a fetus in an immature uterus.[ncbi.nlm.nih.gov]
  • Because of an increased risk of gonadoblastoma, proper early diagnosis and treatment prevent development of malignancies.[ncbi.nlm.nih.gov]
  • Performance of gonadectomy during the first decade appears be a preventive factor for tumor development since these tumors are usually seen during the second decade.[ncbi.nlm.nih.gov]
  • Müllerian structures can be found in some cases only by histologic examination, which should be coupled to preventive gonadectomy because of the risk of tumor formation. Copyright 2015 American Society for Reproductive Medicine.[ncbi.nlm.nih.gov]
  • Chomatin negative Barr bodies Low immunoglobulins levels Prognostic factors High risk for gonadoblastoma (30%) if Y chromosome material is present, which may obliterate testicular elements and cause incorrect diagnosis Treatment Excise gonads early to prevent[pathologyoutlines.com]



  1. 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;89(2):149–151.
  2. Oliveira RM, Verreschi IT, Lipay MV, Eça LP, Guedes AD, Bianco B. Y chromosome in Turner syndrome: review of the literature. Sao Paulo Med J. 2009;127(6):373–378.
  3. Ottolenghi C, Omari S, Garcia-Ortis JE, et al. FOXL2 is required for commitment to ovary differentiation. Hum Mol Genet. 2005;14(14):2053-2062.
  4. MacLaughlin DT, Donahoe PK. Sex determination and differentiation. N Engl J Med. 2004;350(4):367–378.
  5. Ahmed SF, Cheng A, Dovey L, et al. Phenotypic features, androgen receptor binding, and mutational analysis in 278 clinical cases reported as androgen insensitivity syndrome. J Clin Endocrinol Metab. 2000;85(2):658–665.
  6. Kim KR, Kwon Y, Joung JY, Kim KS, Ayala AG, Ro JY. True hermaphroditism and mixed gonadal dysgenesis in young children: a clinicopathologic study of 10 cases. Mod Pathol. 2002;15(10):1013–1019.

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Last updated: 2019-06-28 11:29