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'''XX gonadal dysgenesis''' is a type of female [[hypogonadism]] in which the ovaries do not function to induce [[puberty]] in an otherwise normal girl whose [[karyotype]] is found to be 46,XX. With nonfunctional [[streak ovaries]], she is low in [[estrogen]] levels ([[Hypoestrogenism|hypoestrogenic]]) and has high levels of [[Follicle-stimulating hormone|FSH]] and [[Luteinizing hormone|LH]]. Estrogen and [[progesterone]] therapy is usually then commenced. Some cases are considered a severe version of [[premature ovarian failure]] where the ovaries fail before puberty.<ref>{{cite journal |last1=Ledig |first1=S |last2=Röpke |first2=A |last3=Wieacker |first3=P |title=Copy number variants in premature ovarian failure and ovarian dysgenesis. |journal=Sexual Development |date=September 2010 |volume=4 |issue=4–5 |pages=225–32 |doi=10.1159/000314958 |pmid=20606390|s2cid=20694337 }}</ref>
'''XX gonadal dysgenesis''' is a type of female [[hypogonadism]] in which the ovaries do not function to induce [[puberty]] in a person assigned female at birth, whose [[karyotype]] is 46,XX.<ref name=":0">{{Citation |last=Stafford |first=Diane E. J. |title=Disorders of puberty |date=2023-01-01 |work=Encyclopedia of Child and Adolescent Health (First Edition) |pages=759–779 |editor-last=Halpern-Felsher |editor-first=Bonnie |url=https://www.sciencedirect.com/science/article/abs/pii/B9780128188729000583?via=ihub |access-date=2024-11-24 |place=Oxford |publisher=Academic Press |isbn=978-0-12-818873-6}}</ref> Individuals with XX gonadal dysgenesis have normal-appearing external genitalia as well as Müllerian structures (e.g., cervix, vagina, uterus). Due to the nearly absent or nonfunctional [[streak ovaries]], the individual is low in [[estrogen]] levels ([[Hypoestrogenism|hypoestrogenic]]) and has high levels of follicle-stimulating hormone ([[Follicle-stimulating hormone|FSH]]) and luteinizing hormone ([[Luteinizing hormone|LH]]), hormones that cycle in the reproductive system.<ref name=":1">{{Cite book |last=Thompson |first=Shelby |title=Fanaroff and Martin's Neonatal-Perinatal Medicine |last2=Wherrett |first2=Diane |publisher=Elsevier |year=2025 |isbn=978-0-323-93266-0 |edition=12th |location=Philadelphia, PA |pages=1750-1789 |chapter=Disorders of Sex Development}}</ref> As a result, the diagnosis often occurs after a concern for delayed puberty or [[amenorrhea]]. Treatment generally involves hormone replacement therapy with estrogen and [[progesterone]].<ref name=":2">{{Cite book |last=Netter |first=Frank |title=Netter Collection of Medical Illustrations: Reprodctive System |publisher=Elsevier |year=2025 |isbn=978-0-323-88083-1 |edition=3rd |location=Philadelphia, PA |pages=197-226 |chapter=Ovaries}}</ref>


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== Presentation ==
Some forms of XX gonadal dysgenesis occurs with [[sensorineural deafness]]. This type is also known as '''Perrault syndrome''', an [[autosome|autosomal]] recessive disease affecting both sexes. Males present only with the deafness.<ref>{{cite journal |pmid=25954653 |year=2015 |last1=Sampathkumar |first1=G. |last2=Veerasigamani |first2=N. |title=Perrault syndrome&nbsp;— a rare case report |journal=Journal of Clinical and Diagnostic Research |volume=9 |issue=3 |pages=OD01-2 |doi=10.7860/JCDR/2015/10992.5641 |pmc=4413102 }}</ref>
'''Signs and Symptoms'''


Individuals with XX gonadal dysgenesis appear phenotypical female with normal internal and external genitalia, bilateral streak gonads, and normal stature. Diagnosis commonly occurs in adolescence due to delayed puberty or amenorrhea. Some individuals may have some breast development, secondary amenorrhea, or ovarian follicles on imaging rather than the expected streak or hypoplastic ovaries.<ref>{{Cite book |last=Lobo |first=Roger |title=Comprehensive Gynecology |publisher=Elsevier |year=2022 |isbn=978-0-323-65399-2 |edition=8th |location=Philadelphia, PA |pages=781-800 |chapter=Primary and secondary amenorrhea and precocious puberty}}</ref>
The term "pure gonadal dysgenesis" (PGD) has been used to distinguish a group of patients from gonadal dysgenesis related to [[Turner syndrome]]. In the latter a distinct chromosomal aberration is present, while in PGD the chromosomal constellation is either 46,XX or 46,XY. Thus XX gonadal dysgenesis is also referred to as ''PGD, 46 XX'', and XY gonadal dysgenesis as ''PGD, 46,XY'' or [[Swyer syndrome]].<ref>[http://www.medscape.com/viewarticle/499501_5 Log In Problems<!-- Bot generated title -->]</ref> Patients with PGD have a normal chromosomal constellation but may have localized genetic alterations.

There have been some cases with other associated features such as sensorineural hearing loss (i.e., Perrault Syndrome), neurologic abnormalities, renal disease, malformation syndromes, clitoromegaly, or cerebellar ataxia.<ref name=":12">{{Cite book |last=Thompson |first=Shelby |title=Fanaroff and Martin's Neonatal-Perinatal Medicine |last2=Wherrett |first2=Diane |publisher=Elsevier |year=2025 |isbn=978-0-323-93266-0 |edition=12th |location=Philadelphia, PA |pages=1750-1789 |chapter=Disorders of Sex Development}}</ref><ref>{{Citation |last=Simpson |first=Joe Leigh |title=Germ Cell Failure and Ovarian Resistance: Human Genes and Disorders |date=2004 |work=The Ovary |pages=541–557 |url=https://linkinghub.elsevier.com/retrieve/pii/B9780124445628500331 |access-date=2024-12-01 |publisher=Elsevier |language=en |doi=10.1016/b978-012444562-8/50033-1 |isbn=978-0-12-444562-8 |last2=Rajkovic |first2=Aleksandar}}</ref>


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== Presentation ==
=== Related conditions ===
=== Related conditions ===


The term "pure gonadal dysgenesis" (PGD) has been used to differentiate between gonadal dysgenesis related to [[Turner syndrome]]. Turner syndrome occurs due to partial or complete absence of one of the X chromosomes, resulting in 45,XO or 45,X. Associated characteristics include short stature, a broad shield-like chest, webbed neck, premature ovarian failure, and heart and kidney abnormalities to name a few.<ref>{{Cite book |last=Kikkeri |first=Shankar |title=StatPearls |last2=Nagalli |first2=Shivaraj |date=Aug 8, 2023 |publisher=Treasure Island |location=Florida |chapter=Turner Syndrome}}</ref> People with XX gonadal dysgenesis do not generally have the characteristics listed before, other than the primary ovarian insufficiency.<ref name=":3">{{Cite book |last=Smith |first=Roger |title=Netter's Obstetrics and Gynecology |publisher=Elsevier |year=2024 |isbn=978-0-44310739-9 |edition=4th |location=Philadelphia, PA |pages=428-430 |chapter=Gonadal Dysgenesis}}</ref>
XX gonadal dysgenesis is related to the [[Swyer syndrome]] in as much as both conditions have the same phenotype and clinical issues; however in Swyer syndrome the karyotype is 46,XY, and thus gonadectomy is recommended.<ref>{{cite journal |author=Sebastiano Campo |title=Laparoscopic gonadectomy in two patients with gonadal dysgenesis |journal=The Journal of the American Association of Gynecologic Laparoscopists |year=1998}}</ref>


Meanwhile in PGD the chromosomal constellation is either 46,XX or 46,XY.Thus XX gonadal dysgenesis is also referred to as ''PGD, 46 XX''. Meanwhile, XY gonadal dysgenesis is known as ''PGD, 46,XY'' or [[Swyer syndrome]]. Patients with PGD have a normal chromosomal constellation but may have localized genetic alterations. XX gonadal dysgenesis is related to [[Swyer syndrome]] in as much as both conditions have the same phenotype and clinical issues; however in Swyer syndrome the karyotype is 46,XY. Gonadectomy is recommended in these individuals due to the risk of malignant tumors due to mosaicism in the Y chromosome.<ref name=":22">{{Cite book |last=Netter |first=Frank |title=Netter Collection of Medical Illustrations: Reprodctive System |publisher=Elsevier |year=2025 |isbn=978-0-323-88083-1 |edition=3rd |location=Philadelphia, PA |pages=197-226 |chapter=Ovaries}}</ref>
In [[Turner syndrome]] there is a demonstrable abnormality in or absence of one of the sex chromosomes that is the cause of the development of gonadal dysgenesis. In contrast XX gonadal dysgenesis has a normal female chromosome situation.{{citation needed|date=September 2021}}


Gonadal dygenesis has also been related to other syndromes such as [[WAGR syndrome|WAGR syndome]], [[Denys–Drash syndrome|Denys-Drash Syndrome]], and [[Malouf syndrome]].<ref name=":02">{{Citation |last=Stafford |first=Diane E. J. |title=Disorders of puberty |date=2023-01-01 |work=Encyclopedia of Child and Adolescent Health (First Edition) |pages=759–779 |editor-last=Halpern-Felsher |editor-first=Bonnie |url=https://www.sciencedirect.com/science/article/abs/pii/B9780128188729000583?via=ihub |access-date=2024-11-24 |place=Oxford |publisher=Academic Press |isbn=978-0-12-818873-6}}</ref><ref name=":13">{{Cite book |last=Thompson |first=Shelby |title=Fanaroff and Martin's Neonatal-Perinatal Medicine |last2=Wherrett |first2=Diane |publisher=Elsevier |year=2025 |isbn=978-0-323-93266-0 |edition=12th |location=Philadelphia, PA |pages=1750-1789 |chapter=Disorders of Sex Development}}</ref>
Another type of XX gonadal dysgenesis is known as 46,XX gonadal dysgenesis epibulbar dermoid, which follows the similar symptoms as the regular syndrome, though it also shows signs of [[epibulbar dermoid]] (eye disorder).<ref name=NCBI>{{cite journal |vauthors=Quayle SA, Copeland KC |title=46,XX gonadal dysgenesis with epibulbar dermoid |journal=Am. J. Med. Genet. |volume=40 |issue=1 |pages=75–6 |year=1991 |pmid=1909490 |doi=10.1002/ajmg.1320400114}}</ref><ref>{{RareDiseases|5671|46,XX Gonadal dysgenesis epibulbar dermoid}}</ref><ref>[http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=GB&Expert=1771 ORPHANET&nbsp;– About rare diseases&nbsp;– About orphan drugs<!-- Bot generated title -->] {{webarchive |url=https://web.archive.org/web/20050113144454/http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=GB&Expert=1771 |date=January 13, 2005 }}</ref> It has been suggested to be a new type of syndrome.<ref name=NCBI />


== Pathogenesis ==
== Pathogenesis ==
XX gonadal dysgenesis is thought to be mainly caused by genetic defects in the pathways of ovarian development, specifically via autosomal-recessive inheritance since a positive family history or consanguinity has been noted. However, sporadic cases also have been reported. Ongoing research has identified some implicated genes, listed below, which often are in pathways of gonadal differentiation and formation as well as germ cell migration.<ref name=":14">{{Cite book |last=Thompson |first=Shelby |title=Fanaroff and Martin's Neonatal-Perinatal Medicine |last2=Wherrett |first2=Diane |publisher=Elsevier |year=2025 |isbn=978-0-323-93266-0 |edition=12th |location=Philadelphia, PA |pages=1750-1789 |chapter=Disorders of Sex Development}}</ref><ref>{{Cite journal |last=Laissue |first=Paul |date=2015-08-15 |title=Aetiological coding sequence variants in non-syndromic premature ovarian failure: From genetic linkage analysis to next generation sequencing |url=https://www.sciencedirect.com/science/article/pii/S0303720715002397?via=ihub |journal=Molecular and Cellular Endocrinology |volume=411 |pages=243–257 |doi=10.1016/j.mce.2015.05.005 |issn=0303-7207}}</ref><ref name="Witchel">{{cite book |last1=Witchel |first1=Selma Feldman |title=Pediatric Endocrinology |last2=Lee |first2=Peter A. |date=2014 |isbn=9781455748587 |pages=107–156.e1 |chapter=Ambiguous genitalia |doi=10.1016/B978-1-4557-4858-7.00014-7}}</ref>
The cause of the condition is often unclear.


* [[FSH receptor]]: receptor of follicle stimulating hormone, which is needed for gonadal development; has been seen in familial and sporadic cases<ref>{{Cite journal |last=Lussiana |first=Cristina |last2=Guani |first2=Benedetta |last3=Mari |first3=Caterina |last4=Restagno |first4=Gabriella |last5=Massobrio |first5=Marco |last6=Revelli |first6=Alberto |date=2008-12 |title=Mutations and Polymorphisms of the FSH Receptor (FSHR) Gene: Clinical Implications in Female Fecundity and Molecular Biology of FSHR Protein and Gene |url=https://journals.lww.com/obgynsurvey/abstract/2008/12000/mutations_and_polymorphisms_of_the_fsh_receptor.21.aspx |journal=Obstetrical & Gynecological Survey |language=en-US |volume=63 |issue=12 |pages=785 |doi=10.1097/OGX.0b013e31818957eb |issn=0029-7828}}</ref> <ref>{{Cite journal |last=Nistal |first=Manuel |last2=Paniagua |first2=Ricardo |last3=González-Peramato |first3=Pilar |last4=Reyes-Múgica |first4=Miguel |date=2015-07 |title=Perspectives in Pediatric Pathology, Chapter 5. Gonadal Dysgenesis |url=https://journals.sagepub.com/doi/10.2350/14-04-1471-PB.1 |journal=Pediatric and Developmental Pathology |language=en |volume=18 |issue=4 |pages=259–278 |doi=10.2350/14-04-1471-PB.1 |issn=1093-5266}}</ref>
In cases without hearing involvement, some implicated genes are:<ref name=Witchel>{{cite book |last1=Witchel |first1=Selma Feldman |last2=Lee |first2=Peter A. |chapter=Ambiguous genitalia |title=Pediatric Endocrinology |date=2014 |pages=107–156.e1 |doi=10.1016/B978-1-4557-4858-7.00014-7|isbn=9781455748587 }}</ref>
* [[BMP15]]: x-linked mutations in growth factor expressed during ovarian development<ref>{{Cite journal |last=Laissue |first=Paul |date=2015-08-15 |title=Aetiological coding sequence variants in non-syndromic premature ovarian failure: From genetic linkage analysis to next generation sequencing |url=https://www.sciencedirect.com/science/article/pii/S0303720715002397?via=ihub |journal=Molecular and Cellular Endocrinology |volume=411 |pages=243–257 |doi=10.1016/j.mce.2015.05.005 |issn=0303-7207}}</ref>
* [[FOXL2]], [[NOBOX]], and [[FIGLA]], related to ovarian development.<ref name=Witchel/> FOXL2 mutation can cause [[Blepharophimosis, ptosis, epicanthus inversus syndrome]], which affects the eyes at the same time.<ref name=Simpson/>
* [[NOBOX]]: transcription factor involved in oocyte development<ref name="Witchel" /><ref>{{Citation |last=Simpson |first=JOE LEIGH |title=CHAPTER 32 - Germ Cell Failure and Ovarian Resistance: Human Genes and Disorders |date=2004-01-01 |work=The Ovary (Second Edition) |pages=541–557 |editor-last=Leung |editor-first=PETER C. K. |url=https://linkinghub.elsevier.com/retrieve/pii/B9780124445628500331 |access-date=2024-12-01 |place=San Diego |publisher=Academic Press |doi=10.1016/b978-012444562-8/50033-1 |isbn=978-0-12-444562-8 |last2=Rajkovic |first2=ALEKSANDAR |editor2-last=Adashi |editor2-first=Eli Y.}}</ref><ref>{{Cite journal |last=Simpson |first=Joe Leigh |date=2008 |title=XX Gonadal Dysgenesis and Premature Ovarian Failure in 46,XX Individuals |url=https://www.glowm.com/section-view/item/354 |journal=The Global Library of Women's Medicine |language=en |doi=10.3843/GLOWM.10355 |issn=1756-2228}}</ref>
* [[FSH receptor]], related to signaling. Autosomal recessive.<ref>{{cite journal | last1 = Aittomäki | first1 = K | last2 = Lucena | first2 = JL | last3 = Pakarinen | first3 = P | last4 = Sistonen | first4 = P | last5 = Tapanainen | first5 = J | last6 = Gromoll | first6 = J | last7 = Kaskikari | first7 = R | last8 = Sankila | first8 = EM | last9 = Lehväslaiho | first9 = H | display-authors=8 | title = Mutation in the follicle-stimulating hormone receptor gene causes hereditary hypergonadotropic ovarian failure | journal = Cell | volume = 82 | issue = 6 | pages = 959–68 | year = 1995 | pmid = 7553856 | doi=10.1016/0092-8674(95)90275-9| s2cid = 14748261 | doi-access = free }}</ref>
* [[FIGLA]]: transcription factor involved in activating oocyte-related genes <ref name="Witchel" /><ref>{{Cite journal |last=Er |first=Eren |last2=Aşıkovalı |first2=Semih |last3=Özışık |first3=Hatice |last4=Sağsak |first4=Elif |last5=Gökşen |first5=Damla |last6=Onay |first6=Hüseyin |last7=Saygılı |first7=Füsun |last8=Darcan |first8=Şükran |last9=Özen |first9=Samim |date=2024-01-08 |title=Investigation of the molecular genetic causes of non-syndromic primary ovarian ınsufficiency by next generation sequencing analysis |url=https://www.aem-sbem.com/article/investigation-of-the-molecular-genetic-causes-of-non-syndromic-primary-ovarian-insufficiency-by-next-generation-sequencing-analysis/ |journal=Archives of Endocrinology and Metabolism |language=en |volume=68 |doi=10.20945/2359-4292-2022-0475 |issn=2359-3997 |pmc=PMC10916837 |pmid=37988663}}</ref>
* [[BMP15]], associated with X-linked form.<ref name=Witchel/>
* [[EIF2B2]], [[EIF2B4]], and [[EIF2B5]], responsible for protein production (see [[eIF2]]).<ref name=Witchel/>
* [[PSMC3IP]]: nuclear protein involved in meiosis; seen in cases of autosomal recessive inheritance<ref name="Witchel" />
* [[FOXL2|FOXL2:]] mutation can cause [[blepharophimosis, ptosis, epicanthus inversus syndrome]] (syndrome with eyelid defects and primary ovarian insufficiency)<ref name="Witchel" />
* [[PSMC3IP]], autosomal recessive; mutation reduces estrogen-induced transcription of this gene.<ref name=Witchel/>
* eIFB genes ([[EIF2B2]], [[EIF2B4]], and [[EIF2B5]]): involved in protein production, mutations have been associated with leukodystrophy and primary ovarian failure<ref name="Witchel" /><ref>{{Cite journal |last=Fortuño |first=Cristina |last2=Labarta |first2=Elena |date=2014-12 |title=Genetics of primary ovarian insufficiency: a review |url=http://link.springer.com/10.1007/s10815-014-0342-9 |journal=Journal of Assisted Reproduction and Genetics |language=en |volume=31 |issue=12 |pages=1573–1585 |doi=10.1007/s10815-014-0342-9 |issn=1058-0468 |pmc=PMC4250468 |pmid=25227694}}</ref>
* Various genes involved in [[steroidogenesis]]<ref name=Simpson>{{cite journal |last1=Simpson |first1=J.L. |title=Disorders of the Gonads, Genital Tract, and Genitalia |journal=Reference Module in Biomedical Sciences |date=2014 |pages=B9780128012383055604 |doi=10.1016/B978-0-12-801238-3.05560-4|isbn=9780128012383 }}</ref>


In cases with hearing involvement (Perrault syndrome), the following genes are implicated:<ref>{{Cite web|title=OMIM Phenotypic Series&nbsp;— PS233400|url=https://www.omim.org/phenotypicSeries/PS233400|access-date=2020-11-18|website=www.omim.org}}</ref>
In cases with hearing involvement (Perrault syndrome), the following genes are implicated:<ref>{{Cite web |title=OMIM Phenotypic Series&nbsp;— PS233400 |url=https://www.omim.org/phenotypicSeries/PS233400 |access-date=2020-11-18 |website=www.omim.org}}</ref>
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* [[LARS2]]<ref>{{Cite journal|last1=Pierce|first1=Sarah B.|last2=Gersak|first2=Ksenija|last3=Michaelson-Cohen|first3=Rachel|last4=Walsh|first4=Tom|last5=Lee|first5=Ming K.|last6=Malach|first6=Daniel|last7=Klevit|first7=Rachel E.|last8=King|first8=Mary-Claire|last9=Levy-Lahad|first9=Ephrat|date=April 2013|title=Mutations in LARS2, Encoding Mitochondrial Leucyl-tRNA Synthetase, Lead to Premature Ovarian Failure and Hearing Loss in Perrault Syndrome|url=|journal=The American Journal of Human Genetics|language=en|volume=92|issue=4|pages=614–620|doi=10.1016/j.ajhg.2013.03.007|pmc=3617377|pmid=23541342}}</ref> and [[HARS2]],<ref name="Pierce2011">Pierce SB, Chisholm KM, Lynch ED, Lee MK, Walsh T, Opitz JM, Li W, Klevit RE, King MC (2011) Mutations in mitochondrial histidyl tRNA synthetase HARS2 cause ovarian dysgenesis and sensorineural hearing loss of Perrault syndrome. Proc Natl Acad Sci U S A.</ref> two [[mitochondria]]l [[tRNA synthetase]] genes
* [[HSD17B4]], involved in steroidogenesis and fatty acid metabolism
* [[TWNK]], the mitochondrial [[helicase]]
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* [[ERAL1]], a mitochondrial rRNA chaperone<ref>{{Cite journal|last1=Chatzispyrou|first1=Iliana A.|last2=Alders|first2=Marielle|last3=Guerrero-Castillo|first3=Sergio|last4=Zapata Perez|first4=Ruben|last5=Haagmans|first5=Martin A.|last6=Mouchiroud|first6=Laurent|last7=Koster|first7=Janet|last8=Ofman|first8=Rob|last9=Baas|first9=Frank|last10=Waterham|first10=Hans R.|last11=Spelbrink|first11=Johannes N.|date=2017-07-01|title=A homozygous missense mutation in ERAL1, encoding a mitochondrial rRNA chaperone, causes Perrault syndrome|url=|journal=Human Molecular Genetics|language=en|volume=26|issue=13|pages=2541–2550|doi=10.1093/hmg/ddx152|issn=0964-6906|pmc=5965403|pmid=28449065}}</ref>
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* [[Clp protease family|CLPP]], a mitochondrial protease<ref>{{Cite journal|last1=Jenkinson|first1=Emma M.|last2=Rehman|first2=Atteeq U.|last3=Walsh|first3=Tom|last4=Clayton-Smith|first4=Jill|last5=Lee|first5=Kwanghyuk|last6=Morell|first6=Robert J.|last7=Drummond|first7=Meghan C.|last8=Khan|first8=Shaheen N.|last9=Naeem|first9=Muhammad Asif|last10=Rauf|first10=Bushra|last11=Billington|first11=Neil|date=April 2013|title=Perrault Syndrome Is Caused by Recessive Mutations in CLPP, Encoding a Mitochondrial ATP-Dependent Chambered Protease|url=|journal=The American Journal of Human Genetics|language=en|volume=92|issue=4|pages=605–613|doi=10.1016/j.ajhg.2013.02.013|pmc=3617381|pmid=23541340}}</ref><ref>{{Cite journal|last1=Brodie|first1=Erica J.|last2=Zhan|first2=Hanmiao|last3=Saiyed|first3=Tamanna|last4=Truscott|first4=Kaye N.|last5=Dougan|first5=David A.|date=December 2018|title=Perrault syndrome type 3 caused by diverse molecular defects in CLPP|url=|journal=Scientific Reports|language=en|volume=8|issue=1|pages=12862|doi=10.1038/s41598-018-30311-1|issn=2045-2322|pmc=6110781|pmid=30150665|bibcode=2018NatSR...812862B}}</ref>
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* [[RMND1]], a protein involved in mitochondrial translation; causes kidney problems on top of classical Perrault symptons. Three cases are reported as of 2020.<ref>{{cite journal |pmid=32911714 |year=2020 |last1=Oziębło |first1=D. |last2=Pazik |first2=J. |last3=Stępniak |first3=I. |last4=Skarżyński |first4=H. |last5=Ołdak |first5=M. |title=Two Novel Pathogenic Variants Confirm RMND1 Causative Role in Perrault Syndrome with Renal Involvement |journal=Genes |volume=11 |issue=9 |page=1060 |doi=10.3390/genes11091060 |pmc=7564844 |doi-access=free }}</ref>


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* [[LARS2]]<ref>{{Cite journal |last=Pierce |first=Sarah B. |last2=Gersak |first2=Ksenija |last3=Michaelson-Cohen |first3=Rachel |last4=Walsh |first4=Tom |last5=Lee |first5=Ming K. |last6=Malach |first6=Daniel |last7=Klevit |first7=Rachel E. |last8=King |first8=Mary-Claire |last9=Levy-Lahad |first9=Ephrat |date=2013-04-04 |title=Mutations in LARS2, Encoding Mitochondrial Leucyl-tRNA Synthetase, Lead to Premature Ovarian Failure and Hearing Loss in Perrault Syndrome |url=https://linkinghub.elsevier.com/retrieve/pii/S0002929713001158 |journal=The American Journal of Human Genetics |language=English |volume=92 |issue=4 |pages=614–620 |doi=10.1016/j.ajhg.2013.03.007 |issn=0002-9297 |pmc=PMC3617377 |pmid=23541342}}</ref>, [[HARS2]]<ref>{{Cite journal |last=Pierce |first=Sarah B. |last2=Chisholm |first2=Karen M. |last3=Lynch |first3=Eric D. |last4=Lee |first4=Ming K. |last5=Walsh |first5=Tom |last6=Opitz |first6=John M. |last7=Li |first7=Weiqing |last8=Klevit |first8=Rachel E. |last9=King |first9=Mary-Claire |date=2011-04-19 |title=Mutations in mitochondrial histidyl tRNA synthetase HARS2 cause ovarian dysgenesis and sensorineural hearing loss of Perrault syndrome |url=https://pnas.org/doi/full/10.1073/pnas.1103471108 |journal=Proceedings of the National Academy of Sciences |language=en |volume=108 |issue=16 |pages=6543–6548 |doi=10.1073/pnas.1103471108 |issn=0027-8424 |pmc=PMC3081023 |pmid=21464306}}</ref>: two [[Mitochondria|mitochondrial]] [[tRNA synthetase]] genes
Apparently either the germ cells do not form or interact with the gonadal ridge or undergo accelerated [[atresia]] so that at the end of childhood only a streak gonad is present, unable to induce pubertal changes. As girls' ovaries produce no important body changes before [[puberty]], there is usually no suspicion of a defect of the reproductive system until puberty fails to occur.{{citation needed|date=September 2021}}
* [[HSD17B4]]: involved in steroidogenesis and fatty acid metabolism<ref>{{Cite journal |last=Pierce |first=Sarah B. |last2=Walsh |first2=Tom |last3=Chisholm |first3=Karen M. |last4=Lee |first4=Ming K. |last5=Thornton |first5=Anne M. |last6=Fiumara |first6=Agata |last7=Opitz |first7=John M. |last8=Levy-Lahad |first8=Ephrat |last9=Klevit |first9=Rachel E. |last10=King |first10=Mary-Claire |date=2010-08 |title=Mutations in the DBP-Deficiency Protein HSD17B4 Cause Ovarian Dysgenesis, Hearing Loss, and Ataxia of Perrault Syndrome |url=https://linkinghub.elsevier.com/retrieve/pii/S0002929710003630 |journal=The American Journal of Human Genetics |language=en |volume=87 |issue=2 |pages=282–288 |doi=10.1016/j.ajhg.2010.07.007 |pmc=PMC2917704 |pmid=20673864}}</ref>

* [[TWNK|TWNK:]], the mitochondrial [[helicase]]<ref>{{Cite journal |last=Domínguez-Ruiz |first=María |last2=García-Martínez |first2=Alberto |last3=Corral-Juan |first3=Marc |last4=Pérez-Álvarez |first4=Ángel I. |last5=Plasencia |first5=Ana M. |last6=Villamar |first6=Manuela |last7=Moreno-Pelayo |first7=Miguel A. |last8=Matilla-Dueñas |first8=Antoni |last9=Menéndez-González |first9=Manuel |last10=del Castillo |first10=Ignacio |date=2019-08-28 |title=Perrault syndrome with neurological features in a compound heterozygote for two TWNK mutations: overlap of TWNK-related recessive disorders |url=https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-019-2041-x |journal=Journal of Translational Medicine |volume=17 |issue=1 |pages=290 |doi=10.1186/s12967-019-2041-x |issn=1479-5876 |pmc=PMC6712801 |pmid=31455392}}</ref>
Familial cases of XX gonadal dysgenesis are on record.{{citation needed|date=September 2021}}
⚫
* [[ERAL1]], a mitochondrial rRNA chaperone<ref>{{Cite journal |last=Chatzispyrou |first=Iliana A. |last2=Alders |first2=Marielle |last3=Guerrero-Castillo |first3=Sergio |last4=Zapata Perez |first4=Ruben |last5=Haagmans |first5=Martin A. |last6=Mouchiroud |first6=Laurent |last7=Koster |first7=Janet |last8=Ofman |first8=Rob |last9=Baas |first9=Frank |last10=Waterham |first10=Hans R. |last11=Spelbrink |first11=Johannes N. |last12=Auwerx |first12=Johan |last13=Mannens |first13=Marcel M. |last14=Houtkooper |first14=Riekelt H. |last15=Plomp |first15=Astrid S. |date=2017-07-01 |title=A homozygous missense mutation in ERAL1, encoding a mitochondrial rRNA chaperone, causes Perrault syndrome |url=https://academic.oup.com/hmg/article/26/13/2541/3755423 |journal=Human Molecular Genetics |language=en |volume=26 |issue=13 |pages=2541–2550 |doi=10.1093/hmg/ddx152 |issn=0964-6906 |pmc=PMC5965403 |pmid=28449065}}</ref>
⚫
* [[Clp protease family|CLPP]], a mitochondrial protease<ref>{{Cite journal |last=Jenkinson |first=Emma M. |last2=Rehman |first2=Atteeq U. |last3=Walsh |first3=Tom |last4=Clayton-Smith |first4=Jill |last5=Lee |first5=Kwanghyuk |last6=Morell |first6=Robert J. |last7=Drummond |first7=Meghan C. |last8=Khan |first8=Shaheen N. |last9=Naeem |first9=Muhammad Asif |last10=Rauf |first10=Bushra |last11=Billington |first11=Neil |last12=Schultz |first12=Julie M. |last13=Urquhart |first13=Jill E. |last14=Lee |first14=Ming K. |last15=Berry |first15=Andrew |date=2013-04 |title=Perrault Syndrome Is Caused by Recessive Mutations in CLPP, Encoding a Mitochondrial ATP-Dependent Chambered Protease |url=https://linkinghub.elsevier.com/retrieve/pii/S0002929713001080 |journal=The American Journal of Human Genetics |language=en |volume=92 |issue=4 |pages=605–613 |doi=10.1016/j.ajhg.2013.02.013 |pmc=PMC3617381 |pmid=23541340}}</ref>
⚫
* [[RMND1]], a protein involved in mitochondrial translation; associated with additional renal involvement<ref>{{Cite journal |last=Oziębło |first=Dominika |last2=Pazik |first2=Joanna |last3=Stępniak |first3=Iwona |last4=Skarżyński |first4=Henryk |last5=Ołdak |first5=Monika |date=2020-09-08 |title=Two Novel Pathogenic Variants Confirm RMND1 Causative Role in Perrault Syndrome with Renal Involvement |url=https://www.mdpi.com/2073-4425/11/9/1060 |journal=Genes |language=en |volume=11 |issue=9 |pages=1060 |doi=10.3390/genes11091060 |issn=2073-4425 |pmc=PMC7564844 |pmid=32911714}}</ref>


== Diagnosis ==
== Diagnosis ==
Because of the inability of the streak gonads to produce [[sex hormone]]s (both [[estrogen]]s and [[androgen]]s), most of the [[secondary sex characteristic]]s do not develop. This is especially true of estrogenic changes such as breast development, widening of the pelvis and hips, and [[menstrual cycle|menstrual periods]]. Because the [[adrenal gland]]s can make limited amounts of androgens and are not affected by this syndrome, most of these girls will develop pubic hair, though it often remains sparse.{{citation needed|date=September 2021}}
Because of the inability of the streak gonads to produce [[Sex hormone|sex hormones]] (both [[Estrogen|estrogens]] and [[Androgen|androgens]]), most of the [[Secondary sex characteristic|secondary sex characteristics]] do not develop. This is especially true of estrogenic changes such as breast development, widening of the pelvis and hips, and [[Menstrual cycle|menstrual periods]]. Because the [[Adrenal gland|adrenal glands]] can make limited amounts of androgens and are not affected by this syndrome, most of these individuals will develop pubic hair, though it often remains sparse.<ref>{{Citation |last=Breehl |first=Logen |title=Genetics, Gonadal Dysgenesis |date=2024 |work=StatPearls |url=https://www.ncbi.nlm.nih.gov/books/NBK539886/ |access-date=2024-12-01 |place=Treasure Island (FL) |publisher=StatPearls Publishing |pmid=30969708 |last2=Caban |first2=Omar}}</ref>


Diagnosis usually occurs after evaluation for a concern of [[delayed puberty]]. Next steps involve laboratory studies, such as FSH and LH levels. Other laboratory studies such as [[testosterone]], [[dehydroepiandrosterone]], [[Anti-Müllerian hormone|anti-Mullerian hormone]], [[human chorionic gonadotropin]], [[thyroid-stimulating hormone]], and [[prolactin]] are apart of some algorithms to investigate primary amenorrhea.<ref>{{Cite journal |last=Klein |first=David A. |last2=Poth |first2=Merrily A. |date=2013-06-01 |title=Amenorrhea: An Approach to Diagnosis and Management |url=https://www.aafp.org/pubs/afp/issues/2013/0601/p781.html |journal=American Family Physician |language=en-US |volume=87 |issue=11 |pages=781–788}}</ref><ref>{{Cite journal |last=Kaplowitz |first=P. B. |date=2010-05-01 |title=Delayed Puberty |url=http://pedsinreview.aappublications.org/cgi/doi/10.1542/pir.31-5-189 |journal=Pediatrics in Review |language=en |volume=31 |issue=5 |pages=189–195 |doi=10.1542/pir.31-5-189 |issn=0191-9601}}</ref> Imaging can include a pelvic ultrasound or MRI, which would reveal normal internal genitalia such as a uterus but with streak gonads, which can be small and not easily visualized.<ref>{{Cite journal |last=Chavhan |first=Govind B. |last2=Parra |first2=Dimitri A. |last3=Oudjhane |first3=Kamaldine |last4=Miller |first4=Stephen F. |last5=Babyn |first5=Paul S. |last6=Pippi Salle |first6=Foao L. |date=2008-11 |title=Imaging of Ambiguous Genitalia: Classification and Diagnostic Approach |url=https://pubs.rsna.org/doi/10.1148/rg.287085034 |journal=RadioGraphics |volume=28 |issue=7 |pages=1891–1904 |doi=10.1148/rg.287085034 |issn=0271-5333}}</ref><ref>{{Cite journal |last=Chavhan |first=Govind B. |last2=Parra |first2=Dimitri A. |last3=Oudjhane |first3=Kamaldine |last4=Miller |first4=Stephen F. |last5=Babyn |first5=Paul S. |last6=Pippi Salle |first6=Foao L. |date=2008-11 |title=Imaging of Ambiguous Genitalia: Classification and Diagnostic Approach |url=https://pubs.rsna.org/doi/10.1148/rg.287085034 |journal=RadioGraphics |volume=28 |issue=7 |pages=1891–1904 |doi=10.1148/rg.287085034 |issn=0271-5333}}</ref> Genetic testing involves chromosomal analysis via karyotype to confirm XX chromosomes, rather than XO or XY as discussed in related syndromes above.<ref>{{Citation |last=Breehl |first=Logen |title=Genetics, Gonadal Dysgenesis |date=2024 |work=StatPearls |url=https://www.ncbi.nlm.nih.gov/books/NBK539886/ |access-date=2024-12-01 |place=Treasure Island (FL) |publisher=StatPearls Publishing |pmid=30969708 |last2=Caban |first2=Omar}}</ref><ref>{{Cite journal |last=McCann-Crosby |first=Bonnie |last2=Mansouri |first2=Roshanak |last3=Dietrich |first3=Jennifer E |last4=McCullough |first4=Laurence B |last5=Sutton |first5=V Reid |last6=Austin |first6=Elise G |last7=Schlomer |first7=Bruce |last8=Roth |first8=David R |last9=Karaviti |first9=Lefkothea |last10=Gunn |first10=Sheila |last11=Hicks |first11=M John |last12=Macias |first12=Charles G |date=2014-12 |title=State of the art review in gonadal dysgenesis: challenges in diagnosis and management |url=https://ijpeonline.biomedcentral.com/articles/10.1186/1687-9856-2014-4 |journal=International Journal of Pediatric Endocrinology |language=en |volume=2014 |issue=1 |doi=10.1186/1687-9856-2014-4 |issn=1687-9856 |pmc=PMC3995514 |pmid=24731683}}</ref>
Evaluation of [[delayed puberty]] usually reveals the presence of pubic hair, but elevation of [[gonadotropin]]s, indicating that the pituitary is providing the signal for puberty but the gonads are failing to respond. The next steps of the evaluation usually include checking a [[karyotype]] and imaging of the pelvis. The karyotype reveals XX chromosomes and the imaging demonstrates the presence of a uterus but no ovaries (the streak gonads are not usually seen by most imaging). At this point it is usually possible for a physician to make a diagnosis of XX gonadal dysgenesis.{{citation needed|date=September 2021}}


== Treatment ==
== Treatment ==
Treatment involves hormone replacement therapy that mirrors physiologic levels that would be otherwise provided by functional ovaries. Induction of puberty and menstruation relies on estrogen, which can be given in oral or transdermal forms. Estrogen also has protective effects against osteopenia/osteoporosis as well as cardiovascular health and urogenital atrophy later in life.<ref>{{Cite web |title=Hormone Therapy in Primary Ovarian Insufficiency |url=https://www.acog.org/clinical/clinical-guidance/committee-opinion/articles/2017/05/hormone-therapy-in-primary-ovarian-insufficiency |access-date=2024-12-01 |website=www.acog.org |language=en}}</ref> Progesterone therapy is added after 12 months of estrogen or after menstruation has begun, whichever comes first, which decreases the risk of endometrial hyperplasia and subsequent cancer.<ref>{{Citation |last=Witchel |first=Selma Feldman |title=Ambiguous genitalia |date=2014 |work=Pediatric Endocrinology |pages=107–156.e1 |url=https://linkinghub.elsevier.com/retrieve/pii/B9781455748587000147 |access-date=2024-12-01 |publisher=Elsevier |language=en |doi=10.1016/b978-1-4557-4858-7.00014-7 |isbn=978-1-4557-4858-7 |last2=Lee |first2=Peter A.}}</ref> Combined oral contraceptives can also be used.<ref name=":32">{{Cite book |last=Smith |first=Roger |title=Netter's Obstetrics and Gynecology |publisher=Elsevier |year=2024 |isbn=978-0-44310739-9 |edition=4th |location=Philadelphia, PA |pages=428-430 |chapter=Gonadal Dysgenesis}}</ref>
The consequences to the girl with XX gonadal dysgenesis:{{citation needed|date=September 2021}}

# Her gonads cannot make estrogen, so her breasts will not develop and her uterus will not grow and menstruate until she is given [[estrogen]]. This is often given through the skin now.
In terms of fertility, pregnancy could be facilitated through [[egg donation]] and [[In vitro fertilisation|in vitro fertilization]], as individuals with XX gonadal dysgenesis still have a functional uterus.<ref>{{Cite book |last=Williams |first=Cara |title=Clinical Obstetrics and Gynaecology |date=2023 |publisher=Elsevier |isbn=978-0-7020-8513-0 |edition=Fifth |location=Scotland |pages=33-47 |chapter=Paediatric Gynaecology and Differences in Sex Development}}</ref>
# Her gonads cannot make progesterone, so her menstrual periods will not be predictable until she is given a [[progestin]], still usually as a pill.

# Her gonads cannot produce [[ovum|eggs]] so she will not be able to conceive children naturally. A woman with a uterus but no ovaries may be able to become pregnant by implantation of another woman's fertilized egg ([[embryo transfer]]).
== Prognosis ==
Prognosis is dependent on whether these individuals have any comorbidities or if the gonadal dysgenesis is apart of a syndrome. Without other somatic stigmata, complications include effects on fertility and other comorbidities generally associated with primary ovarian insufficiency such as bone health, cardiovascular risks, and psychosocial stressors.<ref>{{Cite web |title=Primary Ovarian Insufficiency in Adolescents and Young Women |url=https://www.acog.org/clinical/clinical-guidance/committee-opinion/articles/2014/07/primary-ovarian-insufficiency-in-adolescents-and-young-women |access-date=2024-12-01 |website=www.acog.org |language=en}}</ref>


== History ==
== History ==
In 1951, Perrault, Klotz, and Housset reported the association of gonadal dysgenesis and deafness in two sisters, and this presentation is now called [[Perrault syndrome]]. [already has citation]. The first described case of pure gonadal dysgenesis was in 1960, in a patient with presumed Turner syndrome but without the expected stigmata.<ref>{{Cite journal |last=Nistal |first=Manuel |last2=Paniagua |first2=Ricardo |last3=González-Peramato |first3=Pilar |last4=Reyes-Múgica |first4=Miguel |date=2015-07 |title=Perspectives in Pediatric Pathology, Chapter 5. Gonadal Dysgenesis |url=https://journals.sagepub.com/doi/10.2350/14-04-1471-PB.1 |journal=Pediatric and Developmental Pathology |language=en |volume=18 |issue=4 |pages=259–278 |doi=10.2350/14-04-1471-PB.1 |issn=1093-5266}}</ref>
In 1951, Perrault reported the association of gonadal dysgenesis and deafness, now called [[Perrault syndrome]].<ref>Perrault, M.; Klotz, B.; Housset, E.:Deux cas de syndrome de Turner avec surdi-mutite dans une meme fratrie. Bull. Mem. Soc. Med. Hop. Paris 16: 79-84, 1951.</ref>


== See also ==
== See also ==

Revision as of 00:38, 2 December 2024

XX gonadal dysgenesis
Other namesXX ovarian dysgenesis, Perrault syndrome
SpecialtyMedical genetics Edit this on Wikidata

XX gonadal dysgenesis is a type of female hypogonadism in which the ovaries do not function to induce puberty in a person assigned female at birth, whose karyotype is 46,XX.[1] Individuals with XX gonadal dysgenesis have normal-appearing external genitalia as well as Müllerian structures (e.g., cervix, vagina, uterus). Due to the nearly absent or nonfunctional streak ovaries, the individual is low in estrogen levels (hypoestrogenic) and has high levels of follicle-stimulating hormone (FSH) and luteinizing hormone (LH), hormones that cycle in the reproductive system.[2] As a result, the diagnosis often occurs after a concern for delayed puberty or amenorrhea. Treatment generally involves hormone replacement therapy with estrogen and progesterone.[3]

Presentation

Signs and Symptoms

Individuals with XX gonadal dysgenesis appear phenotypical female with normal internal and external genitalia, bilateral streak gonads, and normal stature. Diagnosis commonly occurs in adolescence due to delayed puberty or amenorrhea. Some individuals may have some breast development, secondary amenorrhea, or ovarian follicles on imaging rather than the expected streak or hypoplastic ovaries.[4]

There have been some cases with other associated features such as sensorineural hearing loss (i.e., Perrault Syndrome), neurologic abnormalities, renal disease, malformation syndromes, clitoromegaly, or cerebellar ataxia.[5][6]

The term "pure gonadal dysgenesis" (PGD) has been used to differentiate between gonadal dysgenesis related to Turner syndrome. Turner syndrome occurs due to partial or complete absence of one of the X chromosomes, resulting in 45,XO or 45,X. Associated characteristics include short stature, a broad shield-like chest, webbed neck, premature ovarian failure, and heart and kidney abnormalities to name a few.[7] People with XX gonadal dysgenesis do not generally have the characteristics listed before, other than the primary ovarian insufficiency.[8]

Meanwhile in PGD the chromosomal constellation is either 46,XX or 46,XY.Thus XX gonadal dysgenesis is also referred to as PGD, 46 XX. Meanwhile, XY gonadal dysgenesis is known as PGD, 46,XY or Swyer syndrome. Patients with PGD have a normal chromosomal constellation but may have localized genetic alterations. XX gonadal dysgenesis is related to Swyer syndrome in as much as both conditions have the same phenotype and clinical issues; however in Swyer syndrome the karyotype is 46,XY. Gonadectomy is recommended in these individuals due to the risk of malignant tumors due to mosaicism in the Y chromosome.[9]

Gonadal dygenesis has also been related to other syndromes such as WAGR syndome, Denys-Drash Syndrome, and Malouf syndrome.[10][11]

Pathogenesis

XX gonadal dysgenesis is thought to be mainly caused by genetic defects in the pathways of ovarian development, specifically via autosomal-recessive inheritance since a positive family history or consanguinity has been noted. However, sporadic cases also have been reported. Ongoing research has identified some implicated genes, listed below, which often are in pathways of gonadal differentiation and formation as well as germ cell migration.[12][13][14]

In cases with hearing involvement (Perrault syndrome), the following genes are implicated:[22]

Diagnosis

Because of the inability of the streak gonads to produce sex hormones (both estrogens and androgens), most of the secondary sex characteristics do not develop. This is especially true of estrogenic changes such as breast development, widening of the pelvis and hips, and menstrual periods. Because the adrenal glands can make limited amounts of androgens and are not affected by this syndrome, most of these individuals will develop pubic hair, though it often remains sparse.[30]

Diagnosis usually occurs after evaluation for a concern of delayed puberty. Next steps involve laboratory studies, such as FSH and LH levels. Other laboratory studies such as testosterone, dehydroepiandrosterone, anti-Mullerian hormone, human chorionic gonadotropin, thyroid-stimulating hormone, and prolactin are apart of some algorithms to investigate primary amenorrhea.[31][32] Imaging can include a pelvic ultrasound or MRI, which would reveal normal internal genitalia such as a uterus but with streak gonads, which can be small and not easily visualized.[33][34] Genetic testing involves chromosomal analysis via karyotype to confirm XX chromosomes, rather than XO or XY as discussed in related syndromes above.[35][36]

Treatment

Treatment involves hormone replacement therapy that mirrors physiologic levels that would be otherwise provided by functional ovaries. Induction of puberty and menstruation relies on estrogen, which can be given in oral or transdermal forms. Estrogen also has protective effects against osteopenia/osteoporosis as well as cardiovascular health and urogenital atrophy later in life.[37] Progesterone therapy is added after 12 months of estrogen or after menstruation has begun, whichever comes first, which decreases the risk of endometrial hyperplasia and subsequent cancer.[38] Combined oral contraceptives can also be used.[39]

In terms of fertility, pregnancy could be facilitated through egg donation and in vitro fertilization, as individuals with XX gonadal dysgenesis still have a functional uterus.[40]

Prognosis

Prognosis is dependent on whether these individuals have any comorbidities or if the gonadal dysgenesis is apart of a syndrome. Without other somatic stigmata, complications include effects on fertility and other comorbidities generally associated with primary ovarian insufficiency such as bone health, cardiovascular risks, and psychosocial stressors.[41]

History

In 1951, Perrault, Klotz, and Housset reported the association of gonadal dysgenesis and deafness in two sisters, and this presentation is now called Perrault syndrome. [already has citation]. The first described case of pure gonadal dysgenesis was in 1960, in a patient with presumed Turner syndrome but without the expected stigmata.[42]

See also

References

  1. ^ Stafford, Diane E. J. (2023-01-01), Halpern-Felsher, Bonnie (ed.), "Disorders of puberty", Encyclopedia of Child and Adolescent Health (First Edition), Oxford: Academic Press, pp. 759–779, ISBN 978-0-12-818873-6, retrieved 2024-11-24
  2. ^ Thompson, Shelby; Wherrett, Diane (2025). "Disorders of Sex Development". Fanaroff and Martin's Neonatal-Perinatal Medicine (12th ed.). Philadelphia, PA: Elsevier. pp. 1750–1789. ISBN 978-0-323-93266-0.
  3. ^ Netter, Frank (2025). "Ovaries". Netter Collection of Medical Illustrations: Reprodctive System (3rd ed.). Philadelphia, PA: Elsevier. pp. 197–226. ISBN 978-0-323-88083-1.
  4. ^ Lobo, Roger (2022). "Primary and secondary amenorrhea and precocious puberty". Comprehensive Gynecology (8th ed.). Philadelphia, PA: Elsevier. pp. 781–800. ISBN 978-0-323-65399-2.
  5. ^ Thompson, Shelby; Wherrett, Diane (2025). "Disorders of Sex Development". Fanaroff and Martin's Neonatal-Perinatal Medicine (12th ed.). Philadelphia, PA: Elsevier. pp. 1750–1789. ISBN 978-0-323-93266-0.
  6. ^ Simpson, Joe Leigh; Rajkovic, Aleksandar (2004), "Germ Cell Failure and Ovarian Resistance: Human Genes and Disorders", The Ovary, Elsevier, pp. 541–557, doi:10.1016/b978-012444562-8/50033-1, ISBN 978-0-12-444562-8, retrieved 2024-12-01
  7. ^ Kikkeri, Shankar; Nagalli, Shivaraj (Aug 8, 2023). "Turner Syndrome". StatPearls. Florida: Treasure Island.
  8. ^ Smith, Roger (2024). "Gonadal Dysgenesis". Netter's Obstetrics and Gynecology (4th ed.). Philadelphia, PA: Elsevier. pp. 428–430. ISBN 978-0-44310739-9.
  9. ^ Netter, Frank (2025). "Ovaries". Netter Collection of Medical Illustrations: Reprodctive System (3rd ed.). Philadelphia, PA: Elsevier. pp. 197–226. ISBN 978-0-323-88083-1.
  10. ^ Stafford, Diane E. J. (2023-01-01), Halpern-Felsher, Bonnie (ed.), "Disorders of puberty", Encyclopedia of Child and Adolescent Health (First Edition), Oxford: Academic Press, pp. 759–779, ISBN 978-0-12-818873-6, retrieved 2024-11-24
  11. ^ Thompson, Shelby; Wherrett, Diane (2025). "Disorders of Sex Development". Fanaroff and Martin's Neonatal-Perinatal Medicine (12th ed.). Philadelphia, PA: Elsevier. pp. 1750–1789. ISBN 978-0-323-93266-0.
  12. ^ Thompson, Shelby; Wherrett, Diane (2025). "Disorders of Sex Development". Fanaroff and Martin's Neonatal-Perinatal Medicine (12th ed.). Philadelphia, PA: Elsevier. pp. 1750–1789. ISBN 978-0-323-93266-0.
  13. ^ Laissue, Paul (2015-08-15). "Aetiological coding sequence variants in non-syndromic premature ovarian failure: From genetic linkage analysis to next generation sequencing". Molecular and Cellular Endocrinology. 411: 243–257. doi:10.1016/j.mce.2015.05.005. ISSN 0303-7207.
  14. ^ a b c d e f Witchel, Selma Feldman; Lee, Peter A. (2014). "Ambiguous genitalia". Pediatric Endocrinology. pp. 107–156.e1. doi:10.1016/B978-1-4557-4858-7.00014-7. ISBN 9781455748587.
  15. ^ Lussiana, Cristina; Guani, Benedetta; Mari, Caterina; Restagno, Gabriella; Massobrio, Marco; Revelli, Alberto (2008-12). "Mutations and Polymorphisms of the FSH Receptor (FSHR) Gene: Clinical Implications in Female Fecundity and Molecular Biology of FSHR Protein and Gene". Obstetrical & Gynecological Survey. 63 (12): 785. doi:10.1097/OGX.0b013e31818957eb. ISSN 0029-7828. {{cite journal}}: Check date values in: |date= (help)
  16. ^ Nistal, Manuel; Paniagua, Ricardo; González-Peramato, Pilar; Reyes-Múgica, Miguel (2015-07). "Perspectives in Pediatric Pathology, Chapter 5. Gonadal Dysgenesis". Pediatric and Developmental Pathology. 18 (4): 259–278. doi:10.2350/14-04-1471-PB.1. ISSN 1093-5266. {{cite journal}}: Check date values in: |date= (help)
  17. ^ Laissue, Paul (2015-08-15). "Aetiological coding sequence variants in non-syndromic premature ovarian failure: From genetic linkage analysis to next generation sequencing". Molecular and Cellular Endocrinology. 411: 243–257. doi:10.1016/j.mce.2015.05.005. ISSN 0303-7207.
  18. ^ Simpson, JOE LEIGH; Rajkovic, ALEKSANDAR (2004-01-01), Leung, PETER C. K.; Adashi, Eli Y. (eds.), "CHAPTER 32 - Germ Cell Failure and Ovarian Resistance: Human Genes and Disorders", The Ovary (Second Edition), San Diego: Academic Press, pp. 541–557, doi:10.1016/b978-012444562-8/50033-1, ISBN 978-0-12-444562-8, retrieved 2024-12-01
  19. ^ Simpson, Joe Leigh (2008). "XX Gonadal Dysgenesis and Premature Ovarian Failure in 46,XX Individuals". The Global Library of Women's Medicine. doi:10.3843/GLOWM.10355. ISSN 1756-2228.
  20. ^ Er, Eren; Aşıkovalı, Semih; Özışık, Hatice; Sağsak, Elif; Gökşen, Damla; Onay, Hüseyin; Saygılı, Füsun; Darcan, Şükran; Özen, Samim (2024-01-08). "Investigation of the molecular genetic causes of non-syndromic primary ovarian ınsufficiency by next generation sequencing analysis". Archives of Endocrinology and Metabolism. 68. doi:10.20945/2359-4292-2022-0475. ISSN 2359-3997. PMC 10916837. PMID 37988663.{{cite journal}}: CS1 maint: PMC format (link)
  21. ^ Fortuño, Cristina; Labarta, Elena (2014-12). "Genetics of primary ovarian insufficiency: a review". Journal of Assisted Reproduction and Genetics. 31 (12): 1573–1585. doi:10.1007/s10815-014-0342-9. ISSN 1058-0468. PMC 4250468. PMID 25227694. {{cite journal}}: Check date values in: |date= (help)CS1 maint: PMC format (link)
  22. ^ "OMIM Phenotypic Series — PS233400". www.omim.org. Retrieved 2020-11-18.
  23. ^ Pierce, Sarah B.; Gersak, Ksenija; Michaelson-Cohen, Rachel; Walsh, Tom; Lee, Ming K.; Malach, Daniel; Klevit, Rachel E.; King, Mary-Claire; Levy-Lahad, Ephrat (2013-04-04). "Mutations in LARS2, Encoding Mitochondrial Leucyl-tRNA Synthetase, Lead to Premature Ovarian Failure and Hearing Loss in Perrault Syndrome". The American Journal of Human Genetics. 92 (4): 614–620. doi:10.1016/j.ajhg.2013.03.007. ISSN 0002-9297. PMC 3617377. PMID 23541342.{{cite journal}}: CS1 maint: PMC format (link)
  24. ^ Pierce, Sarah B.; Chisholm, Karen M.; Lynch, Eric D.; Lee, Ming K.; Walsh, Tom; Opitz, John M.; Li, Weiqing; Klevit, Rachel E.; King, Mary-Claire (2011-04-19). "Mutations in mitochondrial histidyl tRNA synthetase HARS2 cause ovarian dysgenesis and sensorineural hearing loss of Perrault syndrome". Proceedings of the National Academy of Sciences. 108 (16): 6543–6548. doi:10.1073/pnas.1103471108. ISSN 0027-8424. PMC 3081023. PMID 21464306.{{cite journal}}: CS1 maint: PMC format (link)
  25. ^ Pierce, Sarah B.; Walsh, Tom; Chisholm, Karen M.; Lee, Ming K.; Thornton, Anne M.; Fiumara, Agata; Opitz, John M.; Levy-Lahad, Ephrat; Klevit, Rachel E.; King, Mary-Claire (2010-08). "Mutations in the DBP-Deficiency Protein HSD17B4 Cause Ovarian Dysgenesis, Hearing Loss, and Ataxia of Perrault Syndrome". The American Journal of Human Genetics. 87 (2): 282–288. doi:10.1016/j.ajhg.2010.07.007. PMC 2917704. PMID 20673864. {{cite journal}}: Check date values in: |date= (help)CS1 maint: PMC format (link)
  26. ^ Domínguez-Ruiz, María; García-Martínez, Alberto; Corral-Juan, Marc; Pérez-Álvarez, Ángel I.; Plasencia, Ana M.; Villamar, Manuela; Moreno-Pelayo, Miguel A.; Matilla-Dueñas, Antoni; Menéndez-González, Manuel; del Castillo, Ignacio (2019-08-28). "Perrault syndrome with neurological features in a compound heterozygote for two TWNK mutations: overlap of TWNK-related recessive disorders". Journal of Translational Medicine. 17 (1): 290. doi:10.1186/s12967-019-2041-x. ISSN 1479-5876. PMC 6712801. PMID 31455392.{{cite journal}}: CS1 maint: PMC format (link) CS1 maint: unflagged free DOI (link)
  27. ^ Chatzispyrou, Iliana A.; Alders, Marielle; Guerrero-Castillo, Sergio; Zapata Perez, Ruben; Haagmans, Martin A.; Mouchiroud, Laurent; Koster, Janet; Ofman, Rob; Baas, Frank; Waterham, Hans R.; Spelbrink, Johannes N.; Auwerx, Johan; Mannens, Marcel M.; Houtkooper, Riekelt H.; Plomp, Astrid S. (2017-07-01). "A homozygous missense mutation in ERAL1, encoding a mitochondrial rRNA chaperone, causes Perrault syndrome". Human Molecular Genetics. 26 (13): 2541–2550. doi:10.1093/hmg/ddx152. ISSN 0964-6906. PMC 5965403. PMID 28449065.{{cite journal}}: CS1 maint: PMC format (link)
  28. ^ Jenkinson, Emma M.; Rehman, Atteeq U.; Walsh, Tom; Clayton-Smith, Jill; Lee, Kwanghyuk; Morell, Robert J.; Drummond, Meghan C.; Khan, Shaheen N.; Naeem, Muhammad Asif; Rauf, Bushra; Billington, Neil; Schultz, Julie M.; Urquhart, Jill E.; Lee, Ming K.; Berry, Andrew (2013-04). "Perrault Syndrome Is Caused by Recessive Mutations in CLPP, Encoding a Mitochondrial ATP-Dependent Chambered Protease". The American Journal of Human Genetics. 92 (4): 605–613. doi:10.1016/j.ajhg.2013.02.013. PMC 3617381. PMID 23541340. {{cite journal}}: Check date values in: |date= (help); no-break space character in |first12= at position 6 (help); no-break space character in |first13= at position 5 (help); no-break space character in |first14= at position 5 (help); no-break space character in |first2= at position 7 (help); no-break space character in |first6= at position 7 (help); no-break space character in |first7= at position 7 (help); no-break space character in |first8= at position 8 (help); no-break space character in |first9= at position 9 (help); no-break space character in |first= at position 5 (help)CS1 maint: PMC format (link)
  29. ^ Oziębło, Dominika; Pazik, Joanna; Stępniak, Iwona; Skarżyński, Henryk; Ołdak, Monika (2020-09-08). "Two Novel Pathogenic Variants Confirm RMND1 Causative Role in Perrault Syndrome with Renal Involvement". Genes. 11 (9): 1060. doi:10.3390/genes11091060. ISSN 2073-4425. PMC 7564844. PMID 32911714.{{cite journal}}: CS1 maint: PMC format (link) CS1 maint: unflagged free DOI (link)
  30. ^ Breehl, Logen; Caban, Omar (2024), "Genetics, Gonadal Dysgenesis", StatPearls, Treasure Island (FL): StatPearls Publishing, PMID 30969708, retrieved 2024-12-01
  31. ^ Klein, David A.; Poth, Merrily A. (2013-06-01). "Amenorrhea: An Approach to Diagnosis and Management". American Family Physician. 87 (11): 781–788.
  32. ^ Kaplowitz, P. B. (2010-05-01). "Delayed Puberty". Pediatrics in Review. 31 (5): 189–195. doi:10.1542/pir.31-5-189. ISSN 0191-9601.
  33. ^ Chavhan, Govind B.; Parra, Dimitri A.; Oudjhane, Kamaldine; Miller, Stephen F.; Babyn, Paul S.; Pippi Salle, Foao L. (2008-11). "Imaging of Ambiguous Genitalia: Classification and Diagnostic Approach". RadioGraphics. 28 (7): 1891–1904. doi:10.1148/rg.287085034. ISSN 0271-5333. {{cite journal}}: Check date values in: |date= (help)
  34. ^ Chavhan, Govind B.; Parra, Dimitri A.; Oudjhane, Kamaldine; Miller, Stephen F.; Babyn, Paul S.; Pippi Salle, Foao L. (2008-11). "Imaging of Ambiguous Genitalia: Classification and Diagnostic Approach". RadioGraphics. 28 (7): 1891–1904. doi:10.1148/rg.287085034. ISSN 0271-5333. {{cite journal}}: Check date values in: |date= (help)
  35. ^ Breehl, Logen; Caban, Omar (2024), "Genetics, Gonadal Dysgenesis", StatPearls, Treasure Island (FL): StatPearls Publishing, PMID 30969708, retrieved 2024-12-01
  36. ^ McCann-Crosby, Bonnie; Mansouri, Roshanak; Dietrich, Jennifer E; McCullough, Laurence B; Sutton, V Reid; Austin, Elise G; Schlomer, Bruce; Roth, David R; Karaviti, Lefkothea; Gunn, Sheila; Hicks, M John; Macias, Charles G (2014-12). "State of the art review in gonadal dysgenesis: challenges in diagnosis and management". International Journal of Pediatric Endocrinology. 2014 (1). doi:10.1186/1687-9856-2014-4. ISSN 1687-9856. PMC 3995514. PMID 24731683. {{cite journal}}: Check date values in: |date= (help)CS1 maint: PMC format (link) CS1 maint: unflagged free DOI (link)
  37. ^ "Hormone Therapy in Primary Ovarian Insufficiency". www.acog.org. Retrieved 2024-12-01.
  38. ^ Witchel, Selma Feldman; Lee, Peter A. (2014), "Ambiguous genitalia", Pediatric Endocrinology, Elsevier, pp. 107–156.e1, doi:10.1016/b978-1-4557-4858-7.00014-7, ISBN 978-1-4557-4858-7, retrieved 2024-12-01
  39. ^ Smith, Roger (2024). "Gonadal Dysgenesis". Netter's Obstetrics and Gynecology (4th ed.). Philadelphia, PA: Elsevier. pp. 428–430. ISBN 978-0-44310739-9.
  40. ^ Williams, Cara (2023). "Paediatric Gynaecology and Differences in Sex Development". Clinical Obstetrics and Gynaecology (Fifth ed.). Scotland: Elsevier. pp. 33–47. ISBN 978-0-7020-8513-0.
  41. ^ "Primary Ovarian Insufficiency in Adolescents and Young Women". www.acog.org. Retrieved 2024-12-01.
  42. ^ Nistal, Manuel; Paniagua, Ricardo; González-Peramato, Pilar; Reyes-Múgica, Miguel (2015-07). "Perspectives in Pediatric Pathology, Chapter 5. Gonadal Dysgenesis". Pediatric and Developmental Pathology. 18 (4): 259–278. doi:10.2350/14-04-1471-PB.1. ISSN 1093-5266. {{cite journal}}: Check date values in: |date= (help)
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