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Pure gonadal dysgenesis 46,XY(46,XY CGD)

MedGen UID:
445380
Concept ID:
C2936694
Disease or Syndrome
Synonyms: 46, XY CGD; 46, XY complete gonadal dysgenesis; 46, XY pure gonadal dysgenesis; 46,XY CGD; 46,XY complete gonadal dysgenesis; 46,XY sex reversal; Gonadal dysgenesis, XY female type
SNOMED CT: Pure gonadal dysgenesis 46,XY (95218005); Swyer syndrome (95218005)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
Y-linked inheritance
MedGen UID:
163055
Concept ID:
C0814045
Genetic Function
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on the Y chromosome.
X-linked recessive inheritance
MedGen UID:
375779
Concept ID:
C1845977
Finding
Source: Orphanet
A mode of inheritance that is observed for recessive traits related to a gene encoded on the X chromosome. In the context of medical genetics, X-linked recessive disorders manifest in males (who have one copy of the X chromosome and are thus hemizygotes), but generally not in female heterozygotes who have one mutant and one normal allele.
 
Related genes: CBX2, DHH, SRY, MAP3K1, NR5A1, NR0B1
 
Monarch Initiative: MONDO:0010765
OMIM® Phenotypic series: PS400044
Orphanet: ORPHA242

Definition

Swyer syndrome is a condition that affects sex development. Sex development usually follows a particular path based on an individual's chromosomes; however, in Swyer syndrome, sex development is not typical for the affected individual's chromosomal pattern.

Chromosomes contain the genetic instructions for how the body develops and functions. People usually have 46 chromosomes in each cell. Two of the 46 chromosomes, known as X and Y, are called sex chromosomes because they help determine whether a person will develop male or female reproductive structures. Girls and women typically have two X chromosomes (46,XX karyotype), while boys and men typically have one X chromosome and one Y chromosome (46,XY karyotype). In Swyer syndrome, individuals have one X chromosome and one Y chromosome in each cell, which is the pattern typically found in boys and men; however, they have female reproductive structures.

Because they appear female on the outside, babies with Swyer syndrome are usually raised as girls and develop a female gender identity, which is a person's sense of their gender (girl, boy, a combination, or neither). Swyer syndrome may be identified before birth, at birth, or later when a child does not go through puberty as usual. Because they do not have functional ovaries that produce hormones, affected individuals often begin hormone replacement therapy during early adolescence to start puberty, causing the breasts and uterus to grow, and eventually leading to menstruation. Hormone replacement therapy is also important for bone health and helps reduce the risk of low bone density (osteopenia) and fragile bones (osteoporosis). Women with Swyer syndrome do not produce eggs (ova), but if they have a uterus, they may be able to become pregnant with a donated egg or embryo.

People with Swyer syndrome have female external genitalia and some female internal reproductive structures. These individuals usually have a uterus and fallopian tubes, but their gonads (ovaries or testes) are not functional. Instead, the gonads are small and underdeveloped and contain little gonadal tissue. These structures are called  streak gonads. The streak gonadal tissue is at risk of developing cancer that is often hard-to-detect, so it is usually removed surgically. Swyer syndrome is also called 46,XY complete gonadal dysgenesis; the medical term “dysgenesis” means "abnormal development." [from MedlinePlus Genetics]

Professional guidelines

PubMed

Capito C, Leclair MD, Arnaud A, David A, Baron S, Corradini N, Héloury Y
J Pediatr Urol 2011 Feb;7(1):72-5. Epub 2010 Feb 11 doi: 10.1016/j.jpurol.2010.01.010. PMID: 20153258

Recent clinical studies

Etiology

Huang H, Wang C, Tian Q
Clin Endocrinol (Oxf) 2017 Apr;86(4):621-627. Epub 2016 Nov 10 doi: 10.1111/cen.13255. PMID: 27862157
Hersmus R, Stoop H, Turbitt E, Oosterhuis JW, Drop SL, Sinclair AH, White SJ, Looijenga LH
BMC Med Genet 2012 Nov 16;13:108. doi: 10.1186/1471-2350-13-108. PMID: 23157850Free PMC Article
Schäffler A, Barth N, Winkler K, Zietz B, Rümmele P, Knüchel R, Schölmerich J, Palitzsch KD
J Clin Endocrinol Metab 2000 Jun;85(6):2287-92. doi: 10.1210/jcem.85.6.6637. PMID: 10852465

Diagnosis

Huang H, Wang C, Tian Q
Clin Endocrinol (Oxf) 2017 Apr;86(4):621-627. Epub 2016 Nov 10 doi: 10.1111/cen.13255. PMID: 27862157
Dai YL, Fu JF, Hong F, Xu S, Shen Z
Acta Paediatr 2011 Jul;100(7):e39-42. Epub 2011 Feb 14 doi: 10.1111/j.1651-2227.2011.02167.x. PMID: 21314844

Prognosis

Huang H, Wang C, Tian Q
Clin Endocrinol (Oxf) 2017 Apr;86(4):621-627. Epub 2016 Nov 10 doi: 10.1111/cen.13255. PMID: 27862157

Clinical prediction guides

Huang H, Wang C, Tian Q
Clin Endocrinol (Oxf) 2017 Apr;86(4):621-627. Epub 2016 Nov 10 doi: 10.1111/cen.13255. PMID: 27862157

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