46,XY complete gonadal dysgenesis

General Information (adopted from Orphanet):

Synonyms, Signs: 46,XY CGD
46,XY pure gonadal dysgenesis
Swyer syndrome
46,XY sex reversal
Number of Symptoms 26
OrphanetNr: 242
OMIM Id: 154230
233420
300018
400044
612965
613080
613762
ICD-10: Q97.3
UMLs: C2936694
MeSH:
MedDRA:
Snomed: 95218005

Prevalence, inheritance and age of onset:

Prevalence: No data available.
Inheritance: Autosomal recessive
X-linked recessive
X-linked
Autosomal dominant
Sporadic
Y-linked
535902; 18000096; 22071891; 26689524 [IBIS]
Age of onset:

Disease classification (adopted from Orphanet):

Parent Diseases: 46,XY disorder of gonadal development
 -Rare developmental defect during embryogenesis
 -Rare endocrine disease
 -Rare genetic disease
 -Rare urogenital disease
Gonadal dysgenesis of gynecological interest
 -Rare genetic disease
 -Rare gynecologic or obstetric disease
Syndrome associated with hypertrophic cardiomyopathy
 -Rare cardiac disease
 -Rare genetic disease
Syndromic lymphedema
 -Rare circulatory system disease
 -Rare developmental defect during embryogenesis
 -Rare genetic disease
 -Rare skin disease

Comment:

46,XY complete gonadal dysgenesis or Swyer syndrome is a disorder of sex development that affect the gonadal development causing a disagreement between 46,XY karyotype, gonadal and phenotypic sex. Individuals are phenotypically women with female genital appearance (PMID:26689524). It occurs in about 1 of 80,000 newborns (PMID:18410658). Several causative genes have been identified up to now, including ARX, ATRX, CBX2, DHH, DMRT1, GATA4, MAMLD1, MAP3K1, NR0B1, NR5A1, SOX9, SRY, WNT4, WT1 and WWOX (PMID:25314337), but in about 70% of cases no genetic cause has been identified (PMID:22071891).

Symptom Information: Sort by abundance 

1
 (HPO:0000098) Tall stature Frequent [IBIS] 25314337 IBIS 74 / 7739
2
 (HPO:0003782) Eunuchoid habitus 13250193 IBIS 8 / 7739
3
 (HPO:0000763) Sensory neuropathy Rare [IBIS] 25927242 IBIS 78 / 7739
4
 (HPO:0003187) Breast hypoplasia Occasional [IBIS] 17% (n=29) 18410658 IBIS 17 / 7739
5
 (HPO:0000938) Osteopenia Frequent [IBIS] 60% (n=20) 18410658 IBIS 138 / 7739
6
 (HPO:0002225) Sparse pubic hair 25927242 IBIS 76 / 7739
7
 (HPO:0000823) Delayed puberty Very frequent [IBIS] 90% (n=29) 18410658 IBIS 65 / 7739
8
 (HPO:0000815) Hypergonadotropic hypogonadism 25927242 IBIS 48 / 7739
9
 (HPO:0000786) Primary amenorrhea Very frequent [IBIS] 25927242 IBIS 61 / 7739
10
 (HPO:0008665) Clitoral hypertrophy 22071891 IBIS 10 / 7739
11
 (HPO:0000037) Male pseudohermaphroditism Very frequent [IBIS] Very frequent [Orphanet] 13250193 IBIS 25 / 7739
12
 (HPO:0000133) Gonadal dysgenesis Very frequent [IBIS] 26689524 IBIS 21 / 7739
13
 (HPO:0000137) Abnormality of the ovary Very frequent [IBIS] Very frequent [Orphanet] 18410658 IBIS 41 / 7739
14
 (HPO:0010464) Streak ovary Frequent [IBIS] 54% (n=22) 18410658 IBIS 8 / 7739
15
 (HPO:0100621) Dysgerminoma Occasional [IBIS] 32% (n=22) 18410658 IBIS 3 / 7739
16
 (HPO:0000151) Aplasia of the uterus 25927242 IBIS 12 / 7739
17
 (HPO:0000013) Hypoplasia of the uterus Very frequent [IBIS] 18410658 IBIS 21 / 7739
18
 (HPO:0012673) Aplasia of the upper vagina 25927242 IBIS 1 / 7739
19
 (HPO:0010789) Abnormality of the Leydig cells 25927242 IBIS 1 / 7739
20
 (HPO:0010468) Aplasia/Hypoplasia of the testes Very frequent [IBIS] 18410658 IBIS 1 / 7739
21
 (HPO:0100617) Testicular seminoma 25927242 IBIS 3 / 7739
22
 (HPO:0000150) Gonadoblastoma Occasional [IBIS] 14% (n=22) 18410658 IBIS 8 / 7739
23
 (HPO:0012245) Sex reversal Very frequent [IBIS] 13250193 IBIS 13 / 7739
24
 (HPO:0000837) Increased circulating gonadotropin level Frequent [IBIS] 25314337 IBIS 12 / 7739
25
 (HPO:0008373) Puberty and gonadal disorders Very frequent [IBIS] Very frequent [Orphanet] 25314337 IBIS 156 / 7739
26
 (HPO:0030008) Cervical agenesis 25927242 IBIS 1 / 7739

Associated genes:

DHH; DAX1; SRY; NR5A1; CBX2; MAP3K1;

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference
DHH rs111033589 pathogenic RCV000005314.2

Additional Information: