| Swyer syndrome |
| Classification and external resources |
| ICD-10 |
Q56.4 |
| ICD-9 |
752.7 |
| OMIM |
400044 |
| DiseasesDB |
31464 |
| MeSH |
D006061 |
Swyer syndrome, or XY gonadal dysgenesis, is a type of hypogonadism in a person whose karyotype is 46,XY. The person is externally female with streak gonads, and left untreated, will not experience puberty. Such gonads are typically surgically removed and a typical medical treatment would include hormone replacement therapy with female hormones.
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Contents
- 1 Swyer syndrome as a form of "pure gonadal dysgenesis"
- 2 Genetic associations
- 3 Pathogenesis
- 4 Diagnosis
- 5 Treatment
- 6 Gonadal dysgenesis and other similar or related conditions
- 7 References
- 8 External links
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Swyer syndrome as a form of "pure gonadal dysgenesis"
There are several forms of gonadal dysgenesis. The term “pure gonadal dysgenesis” (PGD) or Monica F's syndrome has been used to describe conditions with normal sets of sex chromosomes (e.g., 46,XX or 46,XY), as opposed to those whose gonadal dysgenesis results from missing all or part of the second sex chromosome. The latter group includes those with Turner syndrome (e.g., 45,X) and its variants, as well as those with mixed gonadal dysgenesis and a mixture of cell lines, some containing a Y chromosome (e.g., 46,XY/45,X).
Thus Swyer syndrome is referred to as PGD, 46,XY, and XX gonadal dysgenesis as PGD, 46,XX.[1] Patients with PGD have a normal karyotype but may have defects of a specific gene on a chromosome.
Genetic associations
Types include:
| Type |
OMIM |
Gene |
Locus |
| 46,XY GONADAL DYSGENESIS, COMPLETE, SRY-RELATED |
400044 |
SRY |
Yp11.3 |
| 46,XY GONADAL DYSGENESIS, COMPLETE OR PARTIAL, DHH-RELATED |
233420 |
DHH |
12q13.1 |
| 46,XY GONADAL DYSGENESIS, COMPLETE OR PARTIAL, WITH OR WITHOUT ADRENAL FAILURE |
612965 |
NR5A1 |
9q33 |
| 46,XY GONADAL DYSGENESIS, COMPLETE, CBX2-RELATED |
613080 |
CBX2 |
17q25 |
| 46,XY GONADAL DYSGENESIS, COMPLETE OR PARTIAL, WITH 9p24.3 DELETION |
154230 |
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9p24.3 |
Pathogenesis
The first known step of sexual differentiation of a normal XY fetus is the development of testes. The early stages of testicular formation in the second month of gestation requires the action of several genes, of which one of the earliest and most important is SRY, the sex-determining region of the Y chromosome. Mutations of SRY account for many cases of Swyer syndrome.
When such a gene is defective, the indifferent gonads fail to differentiate into testes in an XY (genetically male) fetus. Without testes, no testosterone or antimüllerian hormone (AMH) is produced. Without testosterone, the external genitalia fail to virilize, resulting in normal female genitalia, and the wolffian ducts fail to develop, so no internal male organs are formed. Without AMH, the Müllerian ducts develop into normal internal female organs (uterus, fallopian tubes, cervix, vagina).
A baby who is externally a girl is born and is normal in all anatomic respects except that the child has nonfunctional streak gonads instead of ovaries or testes. As girls' ovaries normally produce no important body changes before puberty, a defect of the reproductive system typically remains unsuspected until puberty fails to occur in people with Swyer syndrome. They appear to be normal girls and are generally considered so.
Diagnosis
Due to 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. As the adrenal glands can make limited amounts of androgens and are not affected by this syndrome, most of these persons will develop pubic hair, though it often remains sparse.
Evaluation of delayed puberty usually reveals elevation of gonadotropins, 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 XY chromosomes and the imaging demonstrates the presence of a uterus but no ovaries (the streak gonads are not usually seen by most imaging). Although an XY karyotype can also indicate a person with complete androgen insensitivity syndrome, the absence of breasts, and the presence of a uterus and pubic hair exclude the possibility. At this point it is usually possible for a physician to make a diagnosis of Swyer syndrome.
Treatment
Upon diagnosis, estrogen and progesterone therapy is typically commenced, prompting the development of female characteristics.
The consequences of streak gonads to a person with Swyer syndrome:
- Gonads cannot make estrogen, so the breasts will not develop and the uterus will not grow and menstruate until estrogen is administered. This is often given transdermally.
- Gonads cannot make progesterone, so menstrual periods will not be predictable until progestin is administered, still usually as a pill.
- Gonads cannot produce eggs so conceiving children naturally is not possible. A woman with a uterus but no ovaries may be able to become pregnant by implantation of another woman's fertilized egg (embryo transfer).
- Streak gonads with Y chromosome-containing cells have a high likelihood of developing cancer, especially gonadoblastoma. Streak gonads are usually removed within a year or so of diagnosis since the cancer can begin during infancy.
Gonadal dysgenesis and other similar or related conditions
Swyer syndrome represents one phenotypic result of a failure of the gonads to develop properly, and hence is part of a class of conditions termed gonadal dysgenesis. There are many forms of gonadal dysgenesis.
Swyer syndrome is an example of a condition in which an externally unambiguous female body carries dysgenetic, atypical, or abnormal gonads. Other examples include complete androgen insensitivity syndrome, partial X chromosome deletions, lipoid congenital adrenal hyperplasia, and Turner syndrome.
References
- ^ Specific Disorders of Ambiguous Genitalia
External links
- Gonadal dysgenesis
- Stoicanescu D, Belengeanu V, et al. (2006). "Complete Gonadal Dysgenesis With XY Chromosomal Constitution". Acta Endocrinologica (Buc) 2 (4): 465–70. doi:10.4183/aeb.2006.465. http://www.acta-endo.ro/actamedica/abstract.php?doi=2006.465.
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Female congenital anomalies of the genitalia, including Intersex and DSD: (Q50–Q52 · 752.0–752.4)
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| Internal |
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Uterine malformation
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Müllerian agenesis · Unicornuate uterus · Uterus didelphys · Bicornuate uterus · Uterine septum · Arcuate uterus
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Vagina
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Vaginal septum · Vaginal atresia
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| External |
Clitoromegaly · Progestin-induced virilisation · Pseudohermaphroditism
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noco/cong/npls, sysi/epon
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proc/asst, drug (G1/G2B/G3CD)
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Extracellular ligand disorders
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| Cytokine |
EDA Hypohidrotic ectodermal dysplasia · Camurati-Engelmann disease
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| Ephrin |
Craniofrontonasal syndrome
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| WNT |
Tetra-amelia syndrome
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| TGF |
OFC 11
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| Fas ligand |
Autoimmune lymphoproliferative syndrome 1B
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| Endothelin |
EDN3 (Waardenburg syndrome IVb, Hirschsprung's disease 4)
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| Other |
DHH (DHH XY gonadal dysgenesis) · BMP15 (Premature ovarian failure 4) · TSHB (Congenital hypothyroidism 4)
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see also intercellular signaling peptides and proteins
B structural (perx, skel, cili, mito, nucl, sclr) · DNA/RNA/protein synthesis (drep, trfc, tscr, tltn) · membrane (icha, slcr, atpa, abct, othr) · transduction (iter, csrc, itra), trfk
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Genetic disorder, protein biosynthesis: Transcription factor/coregulator deficiencies
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| (1) Basic domains |
1.2: Feingold syndrome · Saethre–Chotzen syndrome
1.3: Tietz syndrome
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(2) Zinc finger
DNA-binding domains |
2.1 (Intracellular receptor): Thyroid hormone resistance · Androgen insensitivity syndrome (PAIS, MAIS, CAIS) · Kennedy's disease · PHA1AD pseudohypoaldosteronism · Estrogen insensitivity syndrome · X-linked adrenal hypoplasia congenita · MODY 1 · Familial partial lipodystrophy 3 · SF1 XY gonadal dysgenesis
2.2: Barakat syndrome · Tricho–rhino–phalangeal syndrome
2.3: Greig cephalopolysyndactyly syndrome/Pallister–Hall syndrome · Denys–Drash syndrome · Duane-radial ray syndrome · MODY 7 · MRX 89 · Townes–Brocks syndrome · Acrocallosal syndrome · Myotonic dystrophy 2
2.5: Autoimmune polyendocrine syndrome type 1
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| (3) Helix-turn-helix domains |
3.1: ARX (Ohtahara syndrome, Lissencephaly X2) · HLXB9 (Currarino syndrome) · HOXD13 (SPD1 Synpolydactyly) · IPF1 (MODY 4) · LMX1B (Nail–patella syndrome) · MSX1 (Tooth and nail syndrome, OFC5) · PITX2 (Axenfeld syndrome 1) · POU4F3 (DFNA15) · POU3F4 (DFNX2) · ZEB1 (Posterior polymorphous corneal dystrophy 3, Fuchs' dystrophy 3) · ZEB2 (Mowat–Wilson syndrome)
3.2: PAX2 (Papillorenal syndrome) · PAX3 (Waardenburg syndrome 1&3) · PAX4 (MODY 9) · PAX6 (Gillespie syndrome, Coloboma of optic nerve) · PAX8 (Congenital hypothyroidism 2) · PAX9 (STHAG3)
3.3: FOXC1 (Axenfeld syndrome 3, Iridogoniodysgenesis, dominant type) · FOXC2 (Lymphedema–distichiasis syndrome) · FOXE1 (Bamforth–Lazarus syndrome) · FOXE3 (Anterior segment mesenchymal dysgenesis) · FOXF1 (ACD/MPV) · FOXI1 (Enlarged vestibular aqueduct) · FOXL2 (Premature ovarian failure 3) · FOXP3 (IPEX)
3.5: IRF6 (Van der Woude syndrome, Popliteal pterygium syndrome)
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(4) β-Scaffold factors
with minor groove contacts |
4.2: Hyperimmunoglobulin E syndrome
4.3: Holt–Oram syndrome · Li–Fraumeni syndrome · Ulnar–mammary syndrome
4.7: Campomelic dysplasia · MODY 3 · MODY 5 · SF1 (SRY XY gonadal dysgenesis, Premature ovarian failure 7) · SOX10 (Waardenburg syndrome 4c, Yemenite deaf-blind hypopigmentation syndrome)
4.11: Cleidocranial dysostosis
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| (0) Other transcription factors |
0.6: Kabuki syndrome
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| Ungrouped |
TCF4 (Pitt–Hopkins syndrome) · ZFP57 (TNDM1) · TP63 (Rapp–Hodgkin syndrome/Hay–Wells syndrome/Ectrodactyly–ectodermal dysplasia–cleft syndrome 3/Limb–mammary syndrome/OFC8)
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| Transcription coregulators |
coactivator: CREBBP (Rubinstein–Taybi syndrome)
corepressor: HR (Atrichia with papular lesions)
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see also transcription factors
B structural (perx, skel, cili, mito, nucl, sclr) · DNA/RNA/protein synthesis (drep, trfc, tscr, tltn) · membrane (icha, slcr, atpa, abct, othr) · transduction (iter, csrc, itra), trfk
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