MCID: 46X003
MIFTS: 58

46,xx Testicular Disorder of Sex Development malady

Genetic diseases, Rare diseases, Reproductive diseases, Endocrine diseases, Fetal diseases categories

Summaries for 46,xx Testicular Disorder of Sex Development

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Genetics Home Reference:23 46,XX testicular disorder of sex development is a condition in which individuals with two X chromosomes in each cell, the pattern normally found in females, have a male appearance. People with this disorder have male external genitalia. They generally have small testes and may also have abnormalities such as undescended testes (cryptorchidism) or the urethra opening on the underside of the penis (hypospadias). A small number of affected people have external genitalia that do not look clearly male or clearly female (ambiguous genitalia). Affected children are typically raised as males and have a male gender identity.

MalaCards based summary: 46,xx Testicular Disorder of Sex Development, also known as 46,xx testicular dsd, is related to gonadal dysgenesis and 46xx sex reversal 1, and has symptoms including decreased fertility, polycystic ovaries and primary amenorrhea. An important gene associated with 46,xx Testicular Disorder of Sex Development is BMP15 (bone morphogenetic protein 15), and among its related pathways are Ovarian steroidogenesis and Androgen receptor signaling pathway. The compounds deoxyribonucleic acid and ribonucleic acid have been mentioned in the context of this disorder. Affiliated tissues include ovary, testes and bone, and related mouse phenotypes are growth/size/body and behavior/neurological.

GeneReviews summary for xxms

Aliases & Classifications for 46,xx Testicular Disorder of Sex Development

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Sources:
62UMLS, 21GeneReviews, 43NIH Rare Diseases, 22GeneTests, 23Genetics Home Reference, 49Orphanet, 24GTR, 36MESH via Orphanet, 28ICD10 via Orphanet, 63UMLS via Orphanet
See all sources

46,xx Testicular Disorder of Sex Development, Aliases & Descriptions:

Name: 46,xx Testicular Disorder of Sex Development 21 43 22 23 49 24
46,xx Testicular Dsd 21 43 49
Xx Male Syndrome 21 43 23
Xx Sex Reversal 43 23 62
46,xx Gonadal Dysgenesis 43 49
De La Chapelle Syndrome 43 49
Xx, Male Syndrome 43 49
Follicular Stimulating Hormone-Resistant Ovaries 49
Hypergonadotropic Ovarian Dysgenesis 49
 
46,xx Complete Gonadal Dysgenesis 49
46,xx Pure Gonadal Dysgenesis 49
Xx Female Gonadal Dysgenesis 49
46, Xx Gonadal Sex Reversal 43
46,xx Ovarian Dysgenesis 49
Klinefelter Syndrome 62
46,xx Sex Reversal 23
Fsh-Ro 49
Xx-Gd 49


Classifications:



Characteristics (Orphanet epidemiological data):

49
46,xx gonadal dysgenesis:
Inheritance: Autosomal dominant,Autosomal recessive,Not applicable,X-linked recessive; Prevalence: 1-9/100000 (Europe); Age of onset: Adolescent,Adult; Age of death: normal life expectancy
46,xx testicular disorder of sex development:
Prevalence: 1-9/100000 (Worldwide); Age of onset: Infancy,Neonatal; Age of death: normal life expectancy


External Ids:

Orphanet49 243, 393
MESH via Orphanet36 D023961, D058531
ICD10 via Orphanet28 Q99.1
UMLS via Orphanet63 C0685837, C0949595, C0432475 C2936419, more

Related Diseases for 46,xx Testicular Disorder of Sex Development

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Diseases related to 46,xx Testicular Disorder of Sex Development via text searches within MalaCards or GeneCards/GeneDecks gene sharing:

(show all 39)
idRelated DiseaseScoreTop Affiliating Genes
1gonadal dysgenesis31.1NR5A1, SRY, SOX9
246xx sex reversal 130.7SRY
3ovarian dysgenesis 130.5FSHR
4cryptorchidism30.4NR5A1, SRY
5sry-negative 46,xx testicular disorder of sex development10.7
6sry-positive 46,xx testicular disorder of sex development10.7
7dysgerminoma10.6
8palmoplantar keratoderma - xx sex reversal - predisposition to squamous cell carcinoma10.5
946,xx gonadal dysgenesis epibulbar dermoid10.5
10lung fibrosis - immunodeficiency - 46,xx gonadal dysgenesis10.5
11growth hormone deficiency10.4
12serkal syndrome10.4
13metabolic acidosis10.3
14premature ovarian failure 110.3
15palmoplantar hyperkeratosis with squamous cell carcinoma of skin and sex reversal10.3
1646 xy gonadal dysgenesis10.3
17keratoderma10.3
18hermaphroditism10.2
19frasier syndrome10.0SRY
2046xy sex reversal 310.0NR5A1
21turner syndrome10.0SRY, BMP15
22swyer syndrome10.0SOX9, SRY
23campomelic dysplasia10.0SRY, SOX9
24premature ovarian failure10.0BMP15, FSHR
25male infertility10.0SRY, FSHR
2646,xy disorder of sex development and 46,xy complete gonadal dysgenesis10.0SRY, NR5A1
27amenorrhea10.0FSHR, SRY, BMP15
28azoospermia10.0FSHR, SRY
29congenital adrenal hyperplasia10.0SRY, NR5A1
30hypospadias10.0NR5A1, SRY
31gonadal disease10.0NR5A1, FSHR
32sex cord-gonadal stromal tumor10.0FSHR, NR5A1
33abrikosov's tumor10.0NR5A1, FSHR
34hypogonadism10.0NR5A1, FSHR
35endometriosis10.0NR5A1, FSHR
36polycystic ovary syndrome10.0NR5A1, BMP15, FSHR
37wilms tumor10.0SOX9, SRY, NR5A1
38pituitary adenoma10.0NR5A1, FSHR
39infertility10.0NR5A1, BMP15, SRY, FSHR

Graphical network of the top 20 diseases related to 46,xx Testicular Disorder of Sex Development:



Diseases related to 46,xx testicular disorder of sex development

Symptoms for 46,xx Testicular Disorder of Sex Development

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Symptoms:

 49 (show all 18)
  • abnormal/polycystic ovaries
  • sterility/hypofertility
  • late puberty/hypogonadism/hypogenitalism
  • primary amenorrhea
  • autosomal dominant inheritance
  • osteoporosis/osteopenia/demineralisation/osteomalacia/rickets
  • microcephaly
  • hearing loss/hypoacusia/deafness
  • long hand/arachnodactyly
  • lung fibrosis
  • precocious menopause/secondary amenorrhea
  • ataxia/incoordination/trouble of the equilibrium
  • metabolic anomalies
  • autosomal recessive inheritance
  • x-linked recessive inheritance
  • short stature/dwarfism/nanism
  • ambiguous genitalia
  • small/atrophic/hypoplastic testes/monorchism/microorchidism/anorchia

HPO human phenotypes related to 46,xx Testicular Disorder of Sex Development:

(show all 17)
id Description Frequency HPO Source Accession
1 decreased fertility hallmark (90%) HP:0000144
2 polycystic ovaries hallmark (90%) HP:0000147
3 primary amenorrhea hallmark (90%) HP:0000786
4 abnormality of the testis hallmark (90%) HP:0000035
5 ambiguous genitalia hallmark (90%) HP:0000062
6 reduced bone mineral density typical (50%) HP:0004349
7 microcephaly occasional (7.5%) HP:0000252
8 hearing impairment occasional (7.5%) HP:0000365
9 secondary amenorrhea occasional (7.5%) HP:0000869
10 arachnodactyly occasional (7.5%) HP:0001166
11 abnormality of metabolism/homeostasis occasional (7.5%) HP:0001939
12 pulmonary fibrosis occasional (7.5%) HP:0002206
13 incoordination occasional (7.5%) HP:0002311
14 short stature occasional (7.5%) HP:0004322
15 autosomal dominant inheritance HP:0000006
16 azoospermia HP:0000027
17 true hermaphroditism HP:0010459

Drugs & Therapeutics for 46,xx Testicular Disorder of Sex Development

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Drug clinical trials:

Search ClinicalTrials for 46,xx Testicular Disorder of Sex Development

Search NIH Clinical Center for 46,xx Testicular Disorder of Sex Development

Genetic Tests for 46,xx Testicular Disorder of Sex Development

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Genetic tests related to 46,xx Testicular Disorder of Sex Development:

id Genetic test Affiliating Genes
1 46,xx Testicular Disorder of Sex Development22 24 SRY

Anatomical Context for 46,xx Testicular Disorder of Sex Development

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MalaCards organs/tissues related to 46,xx Testicular Disorder of Sex Development:

33
Ovary, Testes, Bone, Lung, Testis

Animal Models for 46,xx Testicular Disorder of Sex Development or affiliated genes

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MGI Mouse Phenotypes related to 46,xx Testicular Disorder of Sex Development:

37
idDescriptionMGI Source AccessionScoreTop Affiliating Genes
1MP:00053787.6NR5A1, ROCK1, FSHR, SOX9, SOX3
2MP:00053867.5SOX3, SOX9, FSHR, ROCK1, NR5A1
3MP:00053847.4SOX3, SOX9, FSHR, PSMC3IP, ROCK1, NR5A1
4MP:00036317.3SOX3, SOX9, FSHR, ROCK1, NR5A1
5MP:00053767.3SOX3, SOX9, FSHR, PSMC3IP, ROCK1, NR5A1
6MP:00107687.1SOX3, SOX9, FSHR, SRY, ROCK1, NR5A1
7MP:00053797.1NR5A1, SOX3, SOX9, FSHR, PSMC3IP, SRY
8MP:00053897.1SOX3, SOX9, FSHR, PSMC3IP, SRY, BMP15

Publications for 46,xx Testicular Disorder of Sex Development

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Articles related to 46,xx Testicular Disorder of Sex Development:

idTitleAuthorsYear
1
A Korean boy with 46,XX testicular disorder of sex development caused by SOX9 duplication. (25077096)
2014
2
Gene expression profile during testicular development in patients With SRY-negative 46,XX testicular disorder of sex development. (24149105)
2013
3
Two males with SRY-positive 46,XX testicular disorder of sex development. (23110663)
2013
4
De novo 12;17 translocation upstream of SOX9 resulting in 46,XX testicular disorder of sex development. (20082466)
2010
5
46,XX Testicular Disorder of Sex Development (20301589)
1993

Variations for 46,xx Testicular Disorder of Sex Development

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Clinvar genetic disease variations for 46,xx Testicular Disorder of Sex Development:

7 (show all 14)
id Gene Variation Type Significance SNP ID Assembly Location
1BMP15NM_005448.2(BMP15): c.704A> G (p.Tyr235Cys)single nucleotide variantPathogenicrs104894765GRCh37Chr X, 50659132: 50659132
2FSHRNM_000145.3(FSHR): c.566C> T (p.Ala189Val)single nucleotide variantPathogenicrs121909658GRCh37Chr 2, 49210264: 49210264
3FSHRNM_000145.3(FSHR): c.479T> C (p.Ile160Thr)single nucleotide variantPathogenicrs121909659GRCh37Chr 2, 49216161: 49216161
4FSHRNM_000145.3(FSHR): c.1717C> T (p.Arg573Cys)single nucleotide variantPathogenicrs121909660GRCh37Chr 2, 49190243: 49190243
5FSHRNM_000145.3(FSHR): c.1255G> A (p.Ala419Thr)single nucleotide variantPathogenicrs121909661GRCh37Chr 2, 49190705: 49190705
6FSHRNM_000145.3(FSHR): c.1555C> A (p.Pro519Thr)single nucleotide variantPathogenicrs121909662GRCh37Chr 2, 49190405: 49190405
7FSHRNM_000145.3(FSHR): c.1760C> A (p.Pro587His)single nucleotide variantLikely pathogenic, Pathogenicrs386833512GRCh37Chr 2, 49190200: 49190200
8SOX9SOX9, 178-KB DUP, UPSTREAM REGULATORY REGIONduplicationPathogenic
9PSMC3IPPSMC3IP, 3-BP DEL, 600GAGdeletionPathogenic
10FSHRNM_000145.3(FSHR): c.1043C> G (p.Pro348Arg)single nucleotide variantLikely pathogenicrs386833510GRCh37Chr 2, 49190917: 49190917
11FSHRNM_000145.3(FSHR): c.1724C> T (p.Ala575Val)single nucleotide variantLikely pathogenicrs386833511GRCh37Chr 2, 49190236: 49190236
12FSHRNM_000145.3(FSHR): c.1801C> G (p.Leu601Val)single nucleotide variantLikely pathogenicrs386833513GRCh37Chr 2, 49190159: 49190159
13FSHRNM_000145.3(FSHR): c.662T> G (p.Val221Gly)single nucleotide variantLikely pathogenicrs386833514GRCh37Chr 2, 49210057: 49210057
14FSHRNM_000145.3(FSHR): c.671A> T (p.Asp224Val)single nucleotide variantLikely pathogenicrs386833515GRCh37Chr 2, 49196020: 49196020

Expression for genes affiliated with 46,xx Testicular Disorder of Sex Development

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Search GEO for disease gene expression data for 46,xx Testicular Disorder of Sex Development.

Pathways for genes affiliated with 46,xx Testicular Disorder of Sex Development

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Pathways related to 46,xx Testicular Disorder of Sex Development according to GeneCards/GeneDecks:

idSuper pathways (with members indented)ScoreTop Affiliating Genes
19.7BMP15, FSHR
29.6ROCK1, PSMC3IP
39.4NR5A1, FSHR
49.2SOX9, SOX3
59.0SOX3, NR5A1
6
Show member pathways
Wnt Signaling Pathway NetPath38
8.9NR5A1, ROCK1, SOX9
7
Show member pathways
8.3SOX3, SOX9, BMP15, ROCK1

Compounds for genes affiliated with 46,xx Testicular Disorder of Sex Development

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Sources:
45Novoseek, 26HMDB, 13DrugBank, 30IUPHAR, 61Tocris Bioscience
See all sources

Compounds related to 46,xx Testicular Disorder of Sex Development according to GeneCards/GeneDecks:

(show all 12)
idCompoundScoreTop Affiliating Genes
1deoxyribonucleic acid459.7SRY, FSHR
2ribonucleic acid459.2NR5A1, FSHR, SOX9
3dmrt459.1NR5A1, SRY, SOX9
4estradiol45 26 1311.1FSHR, SRY, NR5A1
5progesterone45 30 61 26 1313.0FSHR, BMP15, NR5A1
6cyclic amp45 2610.0NR5A1, FSHR, SOX9
7leucine459.0FSHR, SRY, NR5A1
8zinc45 269.9NR5A1, SRY, SOX9
9testosterone45 61 26 1311.7NR5A1, SRY, FSHR, SOX9
10steroid458.7SOX9, FSHR, SRY, NR5A1
11oligonucleotide458.6NR5A1, SRY, FSHR
12serine458.1SOX9, FSHR, SRY, ROCK1, NR5A1

GO Terms for genes affiliated with 46,xx Testicular Disorder of Sex Development

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Biological processes related to 46,xx Testicular Disorder of Sex Development according to GeneCards/GeneDecks:

idNameGO IDScoreTop Affiliating Genes
1female gamete generationGO:00072929.6BMP15, FSHR
2regulation of cell adhesionGO:00301559.2ROCK1, SOX9
3positive regulation of transcription, DNA-templatedGO:00458939.2BMP15, SRY, SOX9
4male gonad developmentGO:00085849.0SOX9, FSHR, NR5A1
5positive regulation of male gonad developmentGO:020000209.0NR5A1, SRY, SOX9
6Sertoli cell developmentGO:00600098.9FSHR, SOX9, SOX3

Molecular functions related to 46,xx Testicular Disorder of Sex Development according to GeneCards/GeneDecks:

idNameGO IDScoreTop Affiliating Genes
1RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activityGO:00037058.6NR5A1, SRY, SOX9
2DNA bindingGO:00036778.1NR5A1, SRY, PSMC3IP, SOX3

Products for genes affiliated with 46,xx Testicular Disorder of Sex Development

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  • Antibodies
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  • Antibodies
  • Proteins
  • Kits and Assays

Sources for 46,xx Testicular Disorder of Sex Development

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4CDC
15ExPASy
16FMA
24GTR
25HGMD
26HMDB
27ICD10
28ICD10 via Orphanet
29ICD9CM
30IUPHAR
31KEGG
35MeSH
36MESH via Orphanet
37MGI
40NCIt
41NDF-RT
44NINDS
45Novoseek
47OMIM
48OMIM via Orphanet
52PubMed
53QIAGEN
58SNOMED-CT via Orphanet
62UMLS
63UMLS via Orphanet