U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

Gonadal dysgenesis

MedGen UID:
9075
Concept ID:
C0018051
Congenital Abnormality
Synonyms: Dysgenesis, Gonadal; Gonadal Dysgenesis
SNOMED CT: Gonadal dysgenesis (205681004); Gonadal dysgenesis syndrome (38804009)
 
HPO: HP:0000133
Monarch Initiative: MONDO:0001967

Definition

A congenital disorder characterized by the presence of extremely hypoplastic gonads preventing the development of secondary sex characteristics. [from NCI]

Conditions with this feature

Deletion of short arm of chromosome 18
MedGen UID:
96604
Concept ID:
C0432442
Disease or Syndrome
The main clinical manifestations of chromosome 18p deletion syndrome are mental retardation, growth retardation, craniofacial dysmorphism including round face, dysplastic ears, wide mouth and dental anomalies, and abnormalities of the limbs, genitalia, brain, eyes, and heart. The round face characteristic in the neonatal period and childhood may change to a long face with linear growth of the height of the face (summary by Tsukahara et al., 2001).
Ovarian dysgenesis 1
MedGen UID:
215397
Concept ID:
C0949595
Congenital Abnormality
Hypergonadotropic ovarian failure is a heterogeneous disorder that, in the most severe forms, is a result of ovarian dysgenesis. Ovarian dysgenesis accounts for about half the cases of primary amenorrhea (Timmreck and Reindollar, 2003). Genetic Heterogeneity of Ovarian Dysgenesis Even in its isolated form, 46,XX ovarian dysgenesis is etiologically heterogeneous. See ODG2 (300510), caused by mutation in the BMP15 gene (300247); ODG3 (614324), caused by mutation in the PSMC3IP gene (608665); ODG4 (616185), caused by mutation in the MCMDC1 gene (610098); ODG5 (617690), caused by mutation in the SOHLH1 gene (610224); ODG6 (618078), caused by mutation in the NUP107 gene (607617); ODG7 (618117), caused by mutation in the MRPS22 gene (605810); ODG8 (618187), caused by mutation in the ESR2 gene (601663); ODG9 (619665), caused by mutation in the SPIDR gene (615384); and ODG10 (619834), caused by mutation in the ZSWIM7 gene (614535). See also ovarian dysgenesis with sensorineural deafness, or Perrault syndrome (233400).
Drash syndrome
MedGen UID:
181980
Concept ID:
C0950121
Disease or Syndrome
WT1 disorder is characterized by congenital/infantile or childhood onset of steroid-resistant nephrotic syndrome (SRNS), a progressive glomerulopathy that does not respond to standard steroid therapy. Additional common findings can include disorders of testicular development (with or without abnormalities of the external genitalia and/or müllerian structures) and Wilms tumor. Less common findings are congenital anomalies of the kidney and urinary tract (CAKUT) and gonadoblastoma. While various combinations of renal and other findings associated with a WT1 pathogenic variant were designated as certain syndromes in the past, those designations are now recognized to be part of a phenotypic continuum and are no longer clinically helpful.
Frasier syndrome
MedGen UID:
215533
Concept ID:
C0950122
Disease or Syndrome
WT1 disorder is characterized by congenital/infantile or childhood onset of steroid-resistant nephrotic syndrome (SRNS), a progressive glomerulopathy that does not respond to standard steroid therapy. Additional common findings can include disorders of testicular development (with or without abnormalities of the external genitalia and/or müllerian structures) and Wilms tumor. Less common findings are congenital anomalies of the kidney and urinary tract (CAKUT) and gonadoblastoma. While various combinations of renal and other findings associated with a WT1 pathogenic variant were designated as certain syndromes in the past, those designations are now recognized to be part of a phenotypic continuum and are no longer clinically helpful.
46,XY sex reversal 1
MedGen UID:
412662
Concept ID:
C2748896
Disease or Syndrome
Sex reversal in an individual with 46,XY karyotype caused by point mutations or deletions in the SRY gene, encoding sex-determining region Y protein.
Premature ovarian failure 7
MedGen UID:
414115
Concept ID:
C2751825
Disease or Syndrome
Any primary ovarian failure in which the cause of the disease is a mutation in the NR5A1 gene.
46,XY sex reversal 4
MedGen UID:
416704
Concept ID:
C2752149
Congenital Abnormality
Sex reversal in an individual associated with a 9p24.3 deletion.
Lung fibrosis-immunodeficiency-46,XX gonadal dysgenesis syndrome
MedGen UID:
461506
Concept ID:
C3150156
Disease or Syndrome
Lung fibrosis-immunodeficiency-46,XX gonadal dysgenesis syndrome is characterised by immune deficiency, gonadal dysgenesis and fatal lung fibrosis. So far, it has been described in two sisters born to consanguineous parents. Both karyotypes were normal female (46,XX). No genetic anomalies could be identified by comparative genome hybridization analysis of their genomes or by analysis of genes known to be associated with these types of anomalies.
46,XY sex reversal 6
MedGen UID:
462414
Concept ID:
C3151064
Disease or Syndrome
46,XY sex reversal 3
MedGen UID:
483746
Concept ID:
C3489793
Congenital Abnormality
Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 10
MedGen UID:
767295
Concept ID:
C3554381
Disease or Syndrome
Congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies (type A) is an autosomal recessive disorder with characteristic brain and eye malformations, profound mental retardation, congenital muscular dystrophy, and death usually in the first years of life. The brain shows cobblestone lissencephaly, a cortical malformation. The phenotype includes the alternative clinical designations Walker-Warburg syndrome (WWS) and muscle-eye-brain disease (MEB). The disorder represents the most severe end of a phenotypic spectrum of similar disorders resulting from defective glycosylation of alpha-dystroglycan (DAG1; 128239), collectively known as 'dystroglycanopathies' (summary by Vuillaumier-Barrot et al., 2012). For a general phenotypic description and a discussion of genetic heterogeneity of muscular dystrophy-dystroglycanopathy type A, see MDDGA1 (236670).
46,XY sex reversal 9
MedGen UID:
863566
Concept ID:
C4015129
Disease or Syndrome
Perrault syndrome 5
MedGen UID:
863744
Concept ID:
C4015307
Disease or Syndrome
Perrault syndrome is characterized by sensorineural hearing loss (SNHL) in males and females and ovarian dysfunction in females. SNHL is bilateral and ranges from profound with prelingual (congenital) onset to moderate with early-childhood onset. When onset is in early childhood, hearing loss can be progressive. Ovarian dysfunction ranges from gonadal dysgenesis (absent or streak gonads) manifesting as primary amenorrhea to primary ovarian insufficiency (POI) defined as cessation of menses before age 40 years. Fertility in affected males is reported as normal (although the number of reported males is limited). Neurologic features described in some individuals with Perrault syndrome include learning difficulties and developmental delay, cerebellar ataxia, and motor and sensory peripheral neuropathy.
46,XY sex reversal 10
MedGen UID:
897538
Concept ID:
C4225331
Disease or Syndrome
46,XY females with gonadal dysgenesis have streak gonads but look like normal females at birth. They do not develop secondary sexual characteristics at puberty and do not menstruate. They are chromatin-negative and are usually of normal stature, without the somatic stigmata of Turner syndrome (see 163950) (summary by Mann et al., 1983). For a discussion of genetic heterogeneity of 46,XY sex reversal, see SRXY1 (400044).
46,XX sex reversal 4
MedGen UID:
1373282
Concept ID:
C4479552
Congenital Abnormality
Nonsyndromic 46,XX testicular disorders/differences of sex development (DSD) are characterized by: the presence of a 46,XX karyotype; external genitalia ranging from typical male to ambiguous; two testicles; azoospermia; absence of müllerian structures; and absence of other syndromic features, such as congenital anomalies outside of the genitourinary system, learning disorders / cognitive impairment, or behavioral issues. Approximately 85% of individuals with nonsyndromic 46,XX testicular DSD present after puberty with normal pubic hair and normal penile size but small testes, gynecomastia, and sterility resulting from azoospermia. Approximately 15% of individuals with nonsyndromic 46,XX testicular DSD present at birth with ambiguous genitalia. Gender role and gender identity are reported as male. If untreated, males with 46,XX testicular DSD experience the consequences of testosterone deficiency.
Perrault syndrome 1
MedGen UID:
1640257
Concept ID:
C4551721
Disease or Syndrome
Perrault syndrome is characterized by sensorineural hearing loss (SNHL) in males and females and ovarian dysfunction in females. SNHL is bilateral and ranges from profound with prelingual (congenital) onset to moderate with early-childhood onset. When onset is in early childhood, hearing loss can be progressive. Ovarian dysfunction ranges from gonadal dysgenesis (absent or streak gonads) manifesting as primary amenorrhea to primary ovarian insufficiency (POI) defined as cessation of menses before age 40 years. Fertility in affected males is reported as normal (although the number of reported males is limited). Neurologic features described in some individuals with Perrault syndrome include learning difficulties and developmental delay, cerebellar ataxia, and motor and sensory peripheral neuropathy.
Gonadal dysgenesis, dysmorphic facies, retinal dystrophy, and myopathy
MedGen UID:
1679397
Concept ID:
C5193085
Disease or Syndrome
Myoectodermal gonadal dysgenesis syndrome (MEGD) is characterized by 46,XY complete or partial gonadal dysgenesis, or 46,XX gonadal dysgenesis, in association with extragonadal anomalies, including low birth weight, typical facies, rod and cone dystrophy, sensorineural hearing loss, omphalocele, anal atresia, renal agenesis, skeletal abnormalities, dry and scaly skin, severe myopathy, and neuromotor delay. Dysmorphic facial features along with muscular habitus are the hallmarks of the syndrome. Abnormal hair patterning with frontal upsweep and additional whorls, eyebrow abnormalities comprising broad, arched, and sparse or thick eyebrows, underdeveloped alae nasi, smooth philtrum, and low-set ears with overfolded helices facilitate a gestalt diagnosis. (Guran et al., 2019; Altunoglu et al., 2022).
Genitourinary and/or brain malformation syndrome
MedGen UID:
1720440
Concept ID:
C5394158
Disease or Syndrome
Individuals with PPP1R12A-related urogenital and/or brain malformation syndrome (UBMS) usually present with multiple congenital anomalies, commonly including brain and/or urogenital malformations. The brain abnormalities are variable, with the most severe belonging to the holoprosencephaly spectrum and associated with moderate-to-profound intellectual disability, seizures, and feeding difficulties. In individuals without brain involvement, variable degrees of developmental delay and/or intellectual disability may be present, although normal intelligence has been seen in a minority of affected individuals. Eye abnormalities and skeletal issues (kyphoscoliosis, joint contractures) can also be present in individuals of either sex. Regardless of the presence of a brain malformation, affected individuals with a 46,XY chromosome complement may have a disorder of sex development (DSD) with gonadal abnormalities (dysgenetic gonads or streak gonads). Individuals with a 46,XX chromosome complement may have varying degrees of virilization (clitoral hypertrophy, posterior labial fusion, urogenital sinus).
46,XY gonadal dysgenesis-motor and sensory neuropathy syndrome
MedGen UID:
1727162
Concept ID:
C5436061
Disease or Syndrome
46,XY gonadal dysgenesis-motor and sensory neuropathy syndrome is a rare, genetic, developmental defect during embryogenesis disorder characterized by partial (unilateral testis, persistence of Müllerian duct structures) or complete (streak gonads only) gonadal dysgenesis, usually manifesting with primary amenorrhea in individuals with female phenotype but 46,XY karyotype, and sensorimotor dysmyelinating minifascicular polyneuropathy, which presents with numbness, weakness, exercise-induced muscle cramps, sensory disturbances and reduced/absent deep tendon reflexes. Germ cell tumors (seminoma, dysgerminoma, gonadoblastoma) may develop from the gonadal tissue.

Professional guidelines

PubMed

Tahmasbpour Marzouni E, Stern C, Henrik Sinclair A, Tucker EJ
Endocr Rev 2022 Sep 26;43(5):878-906. doi: 10.1210/endrev/bnab047. PMID: 34967858
Kremen J, Chan YM
Curr Opin Endocrinol Diabetes Obes 2019 Feb;26(1):54-59. doi: 10.1097/MED.0000000000000452. PMID: 30507699
Marsh CA, Grimstad FW
Obstet Gynecol Surv 2014 Oct;69(10):603-12. doi: 10.1097/OGX.0000000000000111. PMID: 25336070

Recent clinical studies

Etiology

Zarkower D, Murphy MW
Sex Dev 2022;16(2-3):112-125. Epub 2021 Sep 1 doi: 10.1159/000518272. PMID: 34515237Free PMC Article
Coelingh Bennink HJT, Egberts JFM, Mol JA, Roes KCB, van Diest PJ
J Clin Endocrinol Metab 2020 Sep 1;105(9) doi: 10.1210/clinem/dgaa404. PMID: 32594127
Weidler EM, Pearson M, van Leeuwen K, Garvey E
Semin Pediatr Surg 2019 Oct;28(5):150841. Epub 2019 Sep 19 doi: 10.1016/j.sempedsurg.2019.150841. PMID: 31668295Free PMC Article
King TF, Conway GS
Curr Opin Endocrinol Diabetes Obes 2014 Dec;21(6):504-10. doi: 10.1097/MED.0000000000000113. PMID: 25314337
Skakkebaek NE
Horm Res 2003;60 Suppl 3:49. doi: 10.1159/000074499. PMID: 14671395

Diagnosis

Cicirelli V, Burgio M, Mrenoshki D, Cseh S, Aiudi G, Lacalandra GM
Vet Med Sci 2023 Mar;9(2):600-603. Epub 2023 Jan 3 doi: 10.1002/vms3.1033. PMID: 36597410Free PMC Article
Weidler EM, Pearson M, van Leeuwen K, Garvey E
Semin Pediatr Surg 2019 Oct;28(5):150841. Epub 2019 Sep 19 doi: 10.1016/j.sempedsurg.2019.150841. PMID: 31668295Free PMC Article
Rodriguez-Buritica D
Curr Opin Pediatr 2015 Dec;27(6):675-84. doi: 10.1097/MOP.0000000000000275. PMID: 26335769
King TF, Conway GS
Curr Opin Endocrinol Diabetes Obes 2014 Dec;21(6):504-10. doi: 10.1097/MED.0000000000000113. PMID: 25314337
Michala L, Creighton SM
Best Pract Res Clin Obstet Gynaecol 2010 Apr;24(2):139-48. Epub 2009 Nov 6 doi: 10.1016/j.bpobgyn.2009.09.009. PMID: 19896906

Therapy

Isojima T, Yokoya S
Front Endocrinol (Lausanne) 2022;13:1068128. Epub 2023 Jan 12 doi: 10.3389/fendo.2022.1068128. PMID: 36714599Free PMC Article
King TF, Conway GS
Curr Opin Endocrinol Diabetes Obes 2014 Dec;21(6):504-10. doi: 10.1097/MED.0000000000000113. PMID: 25314337
Trolle C, Hjerrild B, Cleemann L, Mortensen KH, Gravholt CH
Endocrine 2012 Apr;41(2):200-19. Epub 2011 Dec 7 doi: 10.1007/s12020-011-9569-8. PMID: 22147393
Hjerrild BE, Mortensen KH, Gravholt CH
Br Med Bull 2008;86:77-93. Epub 2008 Apr 9 doi: 10.1093/bmb/ldn015. PMID: 18400842
Lee PA, Houk CP, Ahmed SF, Hughes IA; International Consensus Conference on Intersex organized by the Lawson Wilkins Pediatric Endocrine Society and the European Society for Paediatric Endocrinology
Pediatrics 2006 Aug;118(2):e488-500. doi: 10.1542/peds.2006-0738. PMID: 16882788

Prognosis

McElreavey K, Pailhoux E, Bashamboo A
Sex Dev 2022;16(2-3):194-206. Epub 2022 Jul 14 doi: 10.1159/000522004. PMID: 35835064
Sharpe RM
Biochem Soc Trans 2020 Aug 28;48(4):1725-1735. doi: 10.1042/BST20200200. PMID: 32779695Free PMC Article
Matsumoto F, Matsuyama S, Matsui F, Yazawa K, Matsuoka K
Urology 2020 Mar;137:157-160. Epub 2019 Dec 27 doi: 10.1016/j.urology.2019.12.014. PMID: 31883875
Werner R, Mönig I, Lünstedt R, Wünsch L, Thorns C, Reiz B, Krause A, Schwab KO, Binder G, Holterhus PM, Hiort O
PLoS One 2017;12(5):e0176720. Epub 2017 May 1 doi: 10.1371/journal.pone.0176720. PMID: 28459839Free PMC Article
King TF, Conway GS
Curr Opin Endocrinol Diabetes Obes 2014 Dec;21(6):504-10. doi: 10.1097/MED.0000000000000113. PMID: 25314337

Clinical prediction guides

Isojima T, Yokoya S
Front Endocrinol (Lausanne) 2022;13:1068128. Epub 2023 Jan 12 doi: 10.3389/fendo.2022.1068128. PMID: 36714599Free PMC Article
McElreavey K, Pailhoux E, Bashamboo A
Sex Dev 2022;16(2-3):194-206. Epub 2022 Jul 14 doi: 10.1159/000522004. PMID: 35835064
Fiot E, Alauze B, Donadille B, Samara-Boustani D, Houang M, De Filippo G, Bachelot A, Delcour C, Beyler C, Bois E, Bourrat E, Bui Quoc E, Bourcigaux N, Chaussain C, Cohen A, Cohen-Solal M, Da Costa S, Dossier C, Ederhy S, Elmaleh M, Iserin L, Lengliné H, Poujol-Robert A, Roulot D, Viala J, Albarel F, Bismuth E, Bernard V, Bouvattier C, Brac A, Bretones P, Chabbert-Buffet N, Chanson P, Coutant R, de Warren M, Demaret B, Duranteau L, Eustache F, Gautheret L, Gelwane G, Gourbesville C, Grynberg M, Gueniche K, Jorgensen C, Kerlan V, Lebrun C, Lefevre C, Lorenzini F, Manouvrier S, Pienkowski C, Reynaud R, Reznik Y, Siffroi JP, Tabet AC, Tauber M, Vautier V, Tauveron I, Wambre S, Zenaty D, Netchine I, Polak M, Touraine P, Carel JC, Christin-Maitre S, Léger J
Orphanet J Rare Dis 2022 Jul 12;17(Suppl 1):261. doi: 10.1186/s13023-022-02423-5. PMID: 35821070Free PMC Article
Sharpe RM
Biochem Soc Trans 2020 Aug 28;48(4):1725-1735. doi: 10.1042/BST20200200. PMID: 32779695Free PMC Article
Giwercman A, Giwercman YL
Best Pract Res Clin Endocrinol Metab 2011 Apr;25(2):391-402. doi: 10.1016/j.beem.2010.09.011. PMID: 21397206

Recent systematic reviews

Stochholm K, Holmgård C, Davis SM, Gravholt CH, Berglund A
Genet Med 2024 Jan;26(1):100987. Epub 2023 Sep 28 doi: 10.1016/j.gim.2023.100987. PMID: 37781900
Babu R, Shah U
J Pediatr Urol 2021 Feb;17(1):39-47. Epub 2020 Nov 12 doi: 10.1016/j.jpurol.2020.11.017. PMID: 33246831
Taghavi K, Dumble C, Hutson JM, Mushtaq I, Mirjalili SA
J Pediatr Surg 2021 Aug;56(8):1405-1410. Epub 2020 Jun 25 doi: 10.1016/j.jpedsurg.2020.06.023. PMID: 32762939
Nataraja RM, Yeap E, Healy CJ, Nandhra IS, Murphy FL, Hutson JM, Kimber C
Pediatr Surg Int 2018 Mar;34(3):353-361. Epub 2017 Nov 9 doi: 10.1007/s00383-017-4206-0. PMID: 29124402
Castelo-Branco C
Maturitas 2014 Dec;79(4):471-5. Epub 2014 Sep 26 doi: 10.1016/j.maturitas.2014.08.011. PMID: 25438673

Supplemental Content

Table of contents

    Clinical resources

    Practice guidelines

    • PubMed
      See practice and clinical guidelines in PubMed. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.
    • Bookshelf
      See practice and clinical guidelines in NCBI Bookshelf. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.

    Recent activity

    Your browsing activity is empty.

    Activity recording is turned off.

    Turn recording back on

    See more...