Gonadal dysgenesis

{{Short description|Congenital disorder of the reproductive system}} {{Use dmy dates|date=May 2018}} {{confused|Dysgenics}} {{Infobox medical condition (new) | name = Gonadal dysgenesis | synonyms = | image = | caption = | pronounce = | field = | symptoms = | complications = | onset = | duration = | types = | causes = | risks = | diagnosis = pelvic examination (checking for maturation of external internal genitals), general examination (looking for secondary sexual characters), chromosome karyotyping, hormone levels like FSH, LH (which are increased in case of purely XX dysgenesis), family history | differential = | prevention = | treatment = surgery | medication = | prognosis = | frequency = | deaths = }}'''Gonadal dysgenesis''' is classified as any [[Disorders of sex development|congenital developmental disorder of the reproductive system]] characterized by a progressive loss of [[primordial germ cells]] on the developing [[gonad]]s of an embryo.<ref name="renamed_from_1_on_201805291135592">{{cite journal |vauthors=Carreau S, Lejeune H |date=2001 |title=Andrology: Male Reproductive Health and Dysfunction |journal=Andrologie |volume=11 |issue=2 |pages=95–97 |doi=10.1007/BF03034401 |doi-access=free}}</ref><ref name="renamed_from_2_on_20180529113559">{{cite book | vauthors = Hughes I | chapter = The Testes: Disorders of Sexual Differentiation and Puberty in the Male | publisher = Elsevier Health Sciences | pages = 662–685| date = 2008| doi = 10.1016/B978-1-4160-4090-3.X5001-7| pmc = 1491552 | title = Pediatric Endocrinology | journal = Canadian Medical Association Journal | volume = 135 | issue = 5 | isbn = 9781416040903 }}</ref> One type of gonadal dysgenesis is the development of functionless, [[fibrous tissue]], termed streak gonads, instead of reproductive tissue.<ref name="renamed_from_3_on_20180529113559">{{cite web | title = Gonadal Streak. Farlex Partner Medical Dictionary. | url = https://medical-dictionary.thefreedictionary.com/gonadal+streak}}</ref> Streak gonads are a form of [[aplasia]], resulting in hormonal failure that manifests as sexual infantism and [[infertility]], with no initiation of [[puberty]] and [[secondary sex characteristics]].<ref name="renamed_from_4_on_20180529113559">{{cite book | vauthors = Balsamo A, Buonocore G, Bracci R, Weindling M| chapter= Disorders of Sexual Development |title=Neonatology | publisher = Springer | date = 2012}}</ref>

Gonadal development is a process, which is primarily controlled genetically by the chromosomal sex ([[XX chromosome|XX]] or [[XY sex-determination system|XY]]), which directs the formation of the gonad ([[ovary]] or [[testicle]]).<ref name="renamed_from_4_on_20180529113559"/>

Differentiation of the gonads requires a tightly regulated cascade of genetic, molecular and morphogenic events.<ref name="renamed_from_5_on_20180529113559">{{Cite book | vauthors = Pieretti RV, Donahoe PK | chapter= Pathogenesis and Treatment of Disorders of Sexual Development |title=Endocrine Surgery in Children | publisher = Springer | pages = 241–270 | date = 2018 | doi=10.1007/978-3-662-54256-9_18 | isbn = 978-3-662-54254-5 }}</ref> At the formation of the developed gonad, [[steroid]] production influences local and distant receptors for continued [[morphology (biology)|morphological]] and [[biochemical]] changes.<ref name="renamed_from_5_on_20180529113559"/> This results in the [[phenotype]] corresponding to the [[karyotype]] (46,XX for females and 46,XY for males).<ref name="renamed_from_5_on_20180529113559"/>

Gonadal dysgenesis arises from a difference in signalling in this tightly regulated process during early [[foetal development]].<ref name="renamed_from_6_on_20180529113559">{{cite journal | vauthors = Boizet-Bonhoure B | title = Development and Pathology of the Gonad | journal = Seminars in Cell & Developmental Biology |volume = 45 | pages = 57–58 | date = 2015 | pmid = 26653403 | doi= 10.1016/j.semcdb.2015.11.009 }}</ref><ref name="renamed_from_7_on_20180529113559">{{cite journal | vauthors = Jorgensen A, Johansen M, Juul A, Skakkebaek N, Main K, Rajpert-De Meyts E | title = Pathogenesis of germ cell neoplasia in testicular dysgenesis and disorders of sex development | journal = Seminars in Cell & Developmental Biology |volume = 45 | pages = 124–137| date = 2015 | pmid = 26410164| doi=10.1016/j.semcdb.2015.09.013 }}</ref>

Manifestations of gonadal dysgenesis are dependent on the [[aetiology]] and severity of the underlying causes.<ref name="renamed_from_7_on_20180529113559"/>

==Causes== * Pure gonadal dysgenesis 46,XX also known as [[XX gonadal dysgenesis]] * Pure gonadal dysgenesis 46,XY also known as [[XY gonadal dysgenesis]] * [[Mixed gonadal dysgenesis]] also known as partial gonadal dysgenesis, and [[45,X/46,XY mosaicism]] * [[Turner syndrome]] also known as [[45,X]] or 45,X0 * [[endocrine disruptor|Endocrine disruptions]]

==Pathogenesis== ===46,XX gonadal dysgenesis=== {{Main|XX gonadal dysgenesis}}

[[XX gonadal dysgenesis|46,XX gonadal dysgenesis]] is characteristic of [[Hypogonadism|female hypogonadism]] with a [[karyotype]] of 46,XX.<ref name="renamed_from_8_on_20180529113559">{{cite journal | vauthors = Quayle S, Copeland K | title = 46, XX Gonadal Dysgenesis With Epibulbar Dermoid | journal = American Journal of Medical Genetics | volume = 40 | issue = 1 | pages = 4075–4076 | date = 1991| pmid = 1909490 | doi= 10.1002/ajmg.1320400114 }}</ref> Streak ovaries are present with non-functional tissues unable to produce the required sex steroid [[oestrogen]].<ref name="renamed_from_9_on_20180529113559">{{Cite book | vauthors = Nieschlag E, Behre H, Wieacker P, Meschede D, Kamischke A, Kliesch S | chapter= Disorders at the Testicular Level |title=Andrology | publisher = Springer | pages = 193–238 | date = 2010 | isbn=978-3-540-78355-8 | doi=10.1007/978-3-540-78355-8_13 }}</ref> Low levels of oestrogen effect the [[HPG axis]] with no [[feedback]] to the [[anterior pituitary]] to inhibit the secretion of [[Follicle-stimulating hormone|FSH]] and [[Luteinizing hormone|LH]].<ref name="renamed_from_9_on_20180529113559"/>

FSH and LH are secreted at elevated levels.<ref name="renamed_from_9_on_20180529113559"/> Increased levels of these hormones will cause the body to not start [[puberty]], not undergo [[menarche]], and not develop [[secondary sex characteristics]].<ref name="renamed_from_9_on_20180529113559"/><ref name="renamed_from_10_on_20180529113559">{{cite journal | vauthors = Grimbly C, Caluseriu O, Metcalfe P, Jetha M, Rosolowsky E | title = 46, XY disorder of sex development due to 17-beta hydroxysteroid dehydrogenase type 3 deficiency: a plea for timely genetic testing | journal = International Journal of Pediatric Endocrinology |volume = 12 | article-number = 12 | date = 2016 | pmid = 27307783 | pmc = 4908721 | doi=10.1186/s13633-016-0030-x | doi-access = free }}</ref> If ovarian tissue is present and produces some amount of hormones, limited [[menstrual cycles]] can occur.<ref name="renamed_from_9_on_20180529113559"/>

46,XX gonadal dysgenesis can manifest from a variety of causes.<ref name="renamed_from_6_on_20180529113559"/> Interruption during ovarian development in [[embryogenesis]] can cause 46,XX gonadal dysgenesis with cases of changes in the [[FSH receptor]]<ref name="renamed_from_10_on_20180529113559"/><ref name="renamed_from_11_on_20180529113559">{{cite journal | vauthors = Aittomaki K, Lucena J, Pakarinen P, Sistonen P, Tapanainen J, Gromoll J, Kaskikari R, Sankila E | title = Mutations in the follicle-stimulating hormone receptor gene causes hereditary hypergonadotropic ovarian failure | journal = Cell |volume =82 | issue = 6 | pages = 959–968| date = 1995 | pmid = 7553856 | doi= 10.1016/0092-8674(95)90275-9 | s2cid = 14748261 | doi-access = free }}</ref> and [[mutations]] in [[steroidogenic acute regulatory protein]] (StAR protein) which regulates [[steroid hormone]] production.<ref name="renamed_from_10_on_20180529113559"/>

===46,XY gonadal dysgenesis=== {{Main|XY gonadal dysgenesis}}

46,XY gonadal dysgenesis is characteristic of [[Hypogonadism|male hypogonadism]] with [[karyotype]] 46,XY.<ref name="renamed_from_12_on_20180529113559">{{cite journal | vauthors = Chen H, Huang H, Chang T, Lai C, Soong Y | title = Pure XY gonadal dysgenesis and agenesis in monozygotic twins | journal = Fertility and Sterility |volume = 85 | issue = 4 | pages = 1059.9–1059.11| date = 2006 | pmid = 16580399 | doi= 10.1016/j.fertnstert.2005.09.054 | doi-access = free }}</ref> In [[embryogenesis]], the development of the male gonads is primarily controlled by the [[testis determining factor]] located on the sex-determining region of the Y chromosome ([[SRY]]).<ref name="renamed_from_12_on_20180529113559"/> The male gonad is dependent on SRY and the [[signalling pathways]] initiated to several other genes to facilitate [[testis]] development.<ref name="renamed_from_9_on_20180529113559"/>

46,XY gonadal dysgenesis can be caused by mutations in the [[genes]] involved in testis development such as SRY, [[SOX9]], [[WT1]], [[SF1 (gene)|SF1]], and [[DHH (hedgehog)|DHH]].<ref name="renamed_from_9_on_20180529113559"/><ref name="renamed_from_13_on_20180529113559">{{cite journal |vauthors=Barseghyan H, Symon A, Zadikyan M, Almalvez M, Segura E, Eskin A, Bramble M, Arboleda V, Bazter R, Nelson S, Delot E, Harley V, Vilain E |date=2018 |title=Identification of novel candidate genes for 46, XY disorders of sex development (DSD) using a C57BL/6J-Y POS mouse model |journal=Biology of Sex Differences |volume=9 |issue=8 |article-number=8 |doi=10.1186/s13293-018-0167-9 |pmc=5789682 |pmid=29378665 |doi-access=free }}</ref> If a single or combination of these genes are mutated or deleted, [[cell signalling|downstream signalling]] is disrupted, leading to atypical [[Human penis|penis]] and [[scrotum]].<ref name="renamed_from_14_on_20180529113559">{{cite journal | vauthors = Han Y, Wang Y, Li Q, Dai S, He A, Wang E | title = Dysgerminoma in a case of 46, XY pure gonadal dysgenesis (Swyer Syndrome): a case report | journal = Diagnostic Pathology |volume = 6| issue = 84 | article-number = 84 | date = 2011| pmid = 21929773 | pmc = 3182960| doi=10.1186/1746-1596-6-84 | doi-access = free }}</ref>

''Genital Undermasculinization'' is the technical term for partial or complete [[Development of the reproductive system|undifferentiated genitallia]] in individuals with an [[SRY gene]]. [[In utero]], all fetuses are anatomically undifferentiated<ref>{{Citation |last1=Rey |first1=Rodolfo |title=Sexual Differentiation |date=2000 |work=Endotext |editor-last=Feingold |editor-first=Kenneth R. |url=https://www.ncbi.nlm.nih.gov/books/NBK279001/ |access-date=2024-05-27 |place=South Dartmouth (MA) |publisher=MDText.com, Inc. |pmid=25905232 |last2=Josso |first2=Nathalie |last3=Racine |first3=Chrystèle |editor2-last=Anawalt |editor2-first=Bradley |editor3-last=Blackman |editor3-first=Marc R. |editor4-last=Boyce |editor4-first=Alison}}</ref><ref>{{Citation |last=Gilbert |first=Scott F. |title=Chromosomal Sex Determination in Mammals |date=2000 |work=Developmental Biology. 6th edition |url=https://www.ncbi.nlm.nih.gov/books/NBK9967/ |access-date=2024-05-27 |publisher=Sinauer Associates |language=en}}</ref><ref>{{Cite web |last=Digital |first=G. L. P. |date=2017-09-21 |title=Embryos aren't female by 'default' after all, study shows |url=https://geneticliteracyproject.org/2017/09/21/embryos-arent-female-default-study-shows/ |access-date=2024-05-27 |website=Genetic Literacy Project |language=en-US}}</ref> which are then differentiated via androgen's and SRY activation.<ref>{{Cite journal|url=https://jmg.bmj.com/content/36/6/452|title=Incomplete masculinisation of XX subjects carrying the SRY gene on an inactive X chromosome|first1=Kamila|last1=Kusz|first2=Maciej|last2=Kotecki|first3=Alina|last3=Wojda|first4=Maria|last4=Szarras-Czapnik|first5=Anna|last5=Latos-Bielenska|first6=Alina|last6=Warenik-Szymankiewicz|first7=Anna|last7=Ruszczynska-Wolska|first8=Jadwiga|last8=Jaruzelska|date=1 June 1999|journal=Journal of Medical Genetics|volume=36|issue=6|pages=452–456|via=jmg.bmj.com|doi=10.1136/jmg.36.6.452|pmid=10874632|pmc=1734388 }}</ref>

Full undermasculinization results in a fully developed [[vulva]] with testicles inside the body where the ovaries usually are, which is caused by conditions such as [[complete androgen insensitivity syndrome]]. In [[5α-Reductase 2 deficiency]], individuals are born with normal female genitalia, however, during puberty, male differentiation and [[spermatogenesis]] occurs. Partial genital undermasculinization can occur if the body has a [[partial androgen insensitivity syndrome|partial resistance to androgens]], or if genital development is blocked, undermasculization can also be induced by certain drugs and [[hormone]]s. The overall intensity of undermasculinization can manifest itself in [[hypospadias]]. The [[Intersex medical interventions|surgical assignment of newborns]] with ambiguous genitalia to a binary sex for cosmetic purposes is considered a [[Intersex human rights|human rights violation]].<ref>{{Cite web|url=http://www.healthit.gov/isa/uscdi-data/variation-sex-characteristics|title=Variation in Sex Characteristics|website=www.healthit.gov|access-date=5 August 2023|archive-date=14 May 2023|archive-url=https://web.archive.org/web/20230514193618/https://www.healthit.gov/isa/uscdi-data/variation-sex-characteristics|url-status=dead}}</ref><ref>{{cite web|title=''Progress and Politics in the intersex rights movement, Feminist theory in action''|url=http://www.aisia.org/wp-content/uploads/2016/11/Dreger__Herndon_2009.pdf|author1=Alice D. Dreger |author2=April M. Herndon }}</ref>

SRY acts on gene SOX9 which drives [[Sertoli cell]] formation and testis differentiation.<ref name="renamed_from_15_on_20180529113559">{{Cite book | vauthors = Biason-Lauber A | title = Molecular Mechanisms of Cell Differentiation in Gonad Development | chapter = The Battle of the Sexes: Human Sex Development and Its Disorders | series = Results and Problems in Cell Differentiation |volume = 58| pages = 337–382| date = 2006| pmid = 27300185 | doi= 10.1007/978-3-319-31973-5_13| isbn = 978-3-319-31971-1 }}</ref> An absence in SRY causes SOX9 to not be expressed at the usual time or concentration, leading to a decreased [[testosterone]] and [[anti-Müllerian hormone]] production.<ref name="renamed_from_4_on_20180529113559"/>

Lowered levels of testosterone and anti-Müllerian hormone disrupts the development of [[Wolffian ducts]] and internal genitalia that are key to [[male reproductive system|male reproductive tract development]].<ref name="renamed_from_4_on_20180529113559"/> The absence of the steroid hormones commonly associated with males drives [[Müllerian duct]] development and promotes the development of female genitalia, if anti-Müllerian hormone is suppressed or the body is insensitive, [[persistent Müllerian duct syndrome]] occurs when the individual has partial female reproductive, and partial male reproductive organs.<ref name="renamed_from_12_on_20180529113559"/>

Gonadal streaks can replace the tissues of testes, resembling [[stroma of ovary|ovarian stroma]] absent of [[Ovarian follicle|follicle]]s.<ref name="renamed_from_14_on_20180529113559"/> 46,XY gonadal dysgenesis can remain unsuspected until delayed pubertal development is observed.<ref name="renamed_from_14_on_20180529113559"/> Approximately 15% of cases of 46,XY gonadal dysgenesis carry ''de novo'' mutations in the SRY gene,<ref name="renamed_from_16_on_20180529113559">{{cite journal | vauthors = Bashamboo A, McElreavey K | title = Human sex-determination and disorders of sex-development (DSD)| journal = Seminars in Cell & Developmental Biology |volume = 45 | pages = 77–83 | date = 2015 | pmid = 26526145 | doi=10.1016/j.semcdb.2015.10.030}}</ref> with an unknown causation for the remaining portion of 46,XY gonadal dysgenesis persons.<ref name="renamed_from_15_on_20180529113559"/>

===Mixed gonadal dysgenesis=== {{Main|45,X/46,XY mosaicism}}

Mixed gonadal dysgenesis, also known as [[X0/XY mosaicism]] or partial gonadal dysgenesis,<ref name="renamed_from_15_on_20180529113559"/> is a sex development difference associated with sex chromosome [[aneuploidy]] and mosaicism of the [[Y chromosome]].<ref name="renamed_from_14_on_20180529113559"/> Mixed gonadal dysgenesis is the presence of two or more [[germ line]] cells.<ref name="renamed_from_17_on_20180529113559">{{cite journal | vauthors = Donahoe P, Crawford J, Hendren W | title = Mixed Gonadal Dysgenesis, Pathogenesis and Management | journal = Journal of Pediatric Surgery |volume = 14 | issue =3 | pages = 287–300 | date = 1979 | pmid = 480090 | doi=10.1016/s0022-3468(79)80486-8}}</ref>

The degree of development of the male reproductive tract is determined by the ratio of germ line cells expressing the XY genotype.<ref name="renamed_from_15_on_20180529113559"/><ref name="renamed_from_17_on_20180529113559"/>

Manifestations of [[mixed gonadal dysgenesis]] are highly variable with [[asymmetry]] in [[gonadal development]] of testis and streak gonad, accounted for by the percentage of cells expressing XY genotype.<ref name="renamed_from_16_on_20180529113559"/><ref name="renamed_from_17_on_20180529113559"/>

The [[Testicular dysgenesis syndrome|dysgenic testis]] can have an amount of functional tissue which can produce a level of testosterone, which causes [[masculinisation]].<ref name="renamed_from_16_on_20180529113559"/><ref name="renamed_from_17_on_20180529113559"/>

Mixed gonadal dysgenesis is poorly understood at the molecular level.<ref name="renamed_from_17_on_20180529113559"/> The loss of the [[Y chromosome]] can occur from [[Deletion (genetics)|deletions]], [[Chromosomal translocation|translocations]], or migration diffenernce of paired chromosomes during [[cell division]].<ref name="renamed_from_16_on_20180529113559"/><ref name="renamed_from_17_on_20180529113559"/> The chromosomal loss results in partial expression of the SRY gene, giving rise to atypical development of the [[reproductive tract]] and altered hormone levels.<ref name="renamed_from_16_on_20180529113559"/><ref name="renamed_from_17_on_20180529113559"/>

===Turner syndrome=== {{Main|Turner syndrome}}

[[Turner syndrome]], also known as 45,X or 45,X0, is a [[chromosome abnormality|chromosomal abnormality]] characterised by a partial or completely missing second [[X chromosome]],<ref name="renamed_from_4_on_20180529113559"/><ref name="renamed_from_19_on_20180529113559">{{cite web | url= https://www.nichd.nih.gov/health/topics/turner/conditioninfo | title = Turner Syndrome: Condition Information | publisher = Eunice Kennedy Shriver National Institute of Health and Human Development | date = 2012 }}</ref><ref name="renamed_from_20_on_20180529113559">{{Cite book | vauthors = Saenger P, Bondy A | chapter=Turner Syndrome | title = Pediatric Endocrinology |edition=4th | pages = 664–696 | date = 2014| isbn = 9780323315258 }}</ref> giving a chromosomal count of 45, instead of the typical count of 46 chromosomes.<ref name="renamed_from_19_on_20180529113559"/>

Dysregulation in [[meiosis]] signalling to [[germ cells]] during embryogenesis may result in [[nondisjunction]] and [[monosomy X]] from not occurred separation of chromosomes in either the parental [[gamete]] or during early [[human embryogenesis|embryonic divisions]].<ref name="renamed_from_4_on_20180529113559"/><ref name="renamed_from_7_on_20180529113559"/>

The [[aetiology]] of Turner syndrome [[phenotype]] can be the result of [[haploinsufficiency]], where a portion of critical genes are rendered inactive during embryogenesis.<ref name="renamed_from_4_on_20180529113559"/><ref name="renamed_from_19_on_20180529113559"/> Normal [[ovary|ovarian development]] requires these vital regions of the X chromosome that are inactivated.<ref name="renamed_from_4_on_20180529113559"/><ref name="renamed_from_21_on_20180529113559">{{cite journal | vauthors = Elsheikh M, Dunger D, Conway G, Wass J | title = Turners Syndrome in adulthood | journal = Endocrine Reviews |volume = 23 | issue = 1 | pages = 120–140 | date = 2002 | doi= 10.1210/edrv.23.1.0457 | pmid = 11844747 | doi-access = free }}</ref> Clinical manifestation include [[primary amenorrhea]], [[hypergonadotropic hypogonadism]], streak gonads, [[infertility]], and failure to develop [[secondary sex characteristics]].<ref name="renamed_from_20_on_20180529113559"/> Turner syndrome is usually not diagnosed until a delayed onset of [[puberty]] with [[Paramesonephric duct|Müllerian structures]] found to be in infantile stage.<ref name="renamed_from_4_on_20180529113559"/> Physical [[phenotypic]] characteristics include [[short stature]], [[dysmorphic]] features and [[lymphedema]] at birth.<ref name="renamed_from_17_on_20180529113559"/> [[Comorbidities]] include [[heart defects]], [[visual perception|vision]] and [[hearing problems]], [[diabetes]], and low [[thyroid hormone]] production.<ref name="renamed_from_4_on_20180529113559"/><ref name="renamed_from_20_on_20180529113559"/>

===Endocrine disruptions=== {{Main|Endocrine disruptors}}

[[Endocrine disruptors]] interfere with the [[endocrine system]] and [[hormones]].<ref name="renamed_from_22_on_20180529113559">{{cite web | title = Endocrine Disruptors, National Institute of Environmental Health Sciences, 2013| url = https://www.niehs.nih.gov/health/topics/agents/endocrine }}</ref> Hormones are critical for the common events in embryogenesis to occur.<ref name="renamed_from_21_on_20180529113559"/> [[Foetal development]] relies on the proper timing of the delivery of hormones for [[cellular differentiation]] and maturation.<ref name="renamed_from_4_on_20180529113559"/> Disruptions can cause [[Disorders of sex development|sexual development disorders]] leading to gonadal dysgenesis.<ref name="renamed_from_23_on_20180529113559">{{Cite journal | vauthors = Robert S | title = Pesticide atrazine can turn male frogs into females | journal = Berkeley News, University of California |date = 2010| url =http://news.berkeley.edu/2010/03/01/frogs/}}</ref> ==History== Turner syndrome was first described independently by Otto Ulrich in 1930 and [[Henry Turner (endocrinologist)|Henry Turner]] in 1938.<ref name="pmid25105336">{{cite journal | vauthors = Nistal M, Paniagua R, González-Peramato P, Reyes-Múgica M | title = Perspectives in Pediatric Pathology, Chapter 5. Gonadal Dysgenesis | journal = Pediatr. Dev. Pathol. | volume = 18 | issue = 4 | pages = 259–78 | date = 2015 | pmid = 25105336 | doi = 10.2350/14-04-1471-PB.1 | s2cid = 20122694 }}</ref> 46,XX pure gonadal dysgenesis was first reported in 1960.<ref name="pmid25105336" /> 46,XY pure gonadal dysgenesis, also known as Swyer syndrome, was first described by Gim Swyer in 1955.<ref name="pmid25105336" />

== See also == * [[(DoDI) 6130.03, 2018, section 5, 13f and 14m]] * [[Ovotestis]] * [[46 XX]]

== References == {{reflist}}

== External links == {{Medical resources | DiseasesDB = | ICD10 = {{ICD10|Q|99|1|q|90}} | ICD9 = {{ICD9|758.6}} | ICDO = | OMIM = | MedlinePlus = | eMedicineSubj = | eMedicineTopic = | MeshID = D006059 }}

{{DEFAULTSORT:Gonadal Dysgenesis}} [[Category:Congenital disorders of endocrine system]] [[Category:Congenital disorders of genital organs]] [[Category:Intersex topics]] [[Category:Intersex healthcare]] [[Category:Intersex variations]] [[Category:Rare diseases]] [[Category:Sex differences in humans]]