GTS5:Turner syndrome
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Primary Author(s)*
Kathleen Bone, PhD, Medical College of Wisconsin
WHO Classification of Disease
| Structure | Disease |
|---|---|
| Book | Genetic Tumor Syndromes (5th ed.) |
| Category | DNA repair and genomic instability |
| Family | Chromosomal and non-dysjunction (aneuploidy) syndromes |
| Type | N/A |
| Subtype(s) | Turner Syndrome |
Definition / Description of Disease
Turner Syndrome (TS) is a rare chromosomal disorder resulting from complete or partial loss of the second sex chromosome. The most common clinical manifestations include short stature, ovarian failure, primary or secondary amenorrhea associated with hypergonadotropic hypogonadism, congenital lymphedema of the hands and feet, Madelung deformity of the forearm and wrist, webbed neck, cardiac anomalies such as coarctation of the aorta, bicuspid aortic valves, mitral valve prolapse, hypertension, ischemic heart disease and arteriosclerosis, impaired glucose tolerance, thyroid disease and hearing loss[1][2][3][4][5][6]. Despite considerable phenotypic variability, short stature and gonadal dysgenesis are the most consistent findings. While individuals with TS may experience impairments in nonverbal developmental skills, they generally have normal intellectual ability[7].Turner syndrome should be suspected prenatally when a prenatal ultrasound reveals fetal hydrops, cystic hygroma, or cardiac defects. Approximately 50% of TS patients have monosomy X (45,X), while the remaining 50% exhibit various structural abnormalities of the X chromosome or mosaicism with a normal female or normal male cell line.
In individuals with mosaic TS and Y chromosomal material, external genitalia may vary from normal male to ambiguous to female with TS characteristics. The Y chromosome, if present, may also be structurally abnormal. A patient with TS showing evidence of virilization is more likely to be mosaic for a Y-containing cell line, which increases the risk for gonadoblastoma[8]. Molecular screening for Y chromosomal material is recommended in such cases.
Synonyms / Terminology
45,X Syndrome, Monosomy X, Variant Turner Syndrome, Mosaic Turner Syndrome, Congenital Ovarian Hypoplasia Syndrome (historical), Ullrich-Turner Syndrome (historical), Bonnevie-Ullrich syndrome (historical), 45,XO (historical, not recommended) (Instructions: Include currently used terms and major historical ones, adding “(historical)” after the latter.)
Epidemiology / Prevalence
TS and its variants occur in approximately 1 in 2,000 to 1 in 2,500 live-born females[9][10]. However, TS is among the most common chromosomal disorders, affecting 1–2% of conceptions, with approximately 99% of affected pregnancies resulting in loss[11]. The true prevalence of TS is difficult to determine, as many individuals remain undiagnosed or are only diagnosed later in adulthood[12].
Genetic Abnormalities: Germline
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| Gene | Genetic Variant or Variant Type | Molecular Pathogenesis | Inheritance, Penetrance, Expressivity | Notes |
| EXAMPLE: BRCA1 | EXAMPLE: Many | EXAMPLE: Multiple variant types leading to loss of function | ||
| EXAMPLE: Gene X | EXAMPLE: List the specific mutation |
Genetic Abnormalities: Somatic
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| Gene | Genetic Variant or Variant Type | Molecular Pathogenesis | Inheritance, Penetrance, Expressivity | Notes |
| EXAMPLE: BRCA | EXAMPLE: Biallelic inactivation variants | EXAMPLE: Second hit mutation can occur as copy neutral LOH, inactivating mutation, deletion, promoter hypermethylation, or a structural abnormality disrupting the gene. | ||
| EXAMPLE: BRCA | EXAMPLE: Gain | EXAMPLE:After exposure to certain therapies (e.g. PARP inhibitors), a second mutation may restore gene function as a resistance mechanism. |
Genes and Main Pathways Involved
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| Gene; Genetic Alteration | Pathway | Pathophysiologic Outcome |
|---|---|---|
| EXAMPLE: BRAF and MAP2K1; Activating mutations | EXAMPLE: MAPK signaling | EXAMPLE: Increased cell growth and proliferation |
| EXAMPLE: CDKN2A; Inactivating mutations | EXAMPLE: Cell cycle regulation | EXAMPLE: Unregulated cell division |
| EXAMPLE: KMT2C and ARID1A; Inactivating mutations | EXAMPLE: Histone modification, chromatin remodeling | EXAMPLE: Abnormal gene expression program |
Genetic Diagnostic Testing Methods
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Additional Information
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Links
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References
- ↑ Gravholt, Claus H. (2005-11). "Clinical practice in Turner syndrome". Nature Clinical Practice. Endocrinology & Metabolism. 1 (1): 41–52. doi:10.1038/ncpendmet0024. ISSN 1745-8366. PMID 16929365. Check date values in:
|date=(help) - ↑ Bondy, Carolyn A.; et al. (2006-07). "Investigation of cardiac status and bone mineral density in Turner syndrome". Growth hormone & IGF research: official journal of the Growth Hormone Research Society and the International IGF Research Society. 16 Suppl A: S103–108. doi:10.1016/j.ghir.2006.03.008. ISSN 1096-6374. PMID 16624607. Check date values in:
|date=(help) - ↑ Dhooge, Ingeborg J. M.; et al. (2005-03). "Otologic disease in turner syndrome". Otology & Neurotology: Official Publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology. 26 (2): 145–150. doi:10.1097/00129492-200503000-00003. ISSN 1531-7129. PMID 15793396. Check date values in:
|date=(help) - ↑ Güngör, N.; et al. (2000-10). "High frequency hearing loss in Ullrich-Turner syndrome". European Journal of Pediatrics. 159 (10): 740–744. doi:10.1007/pl00008338. ISSN 0340-6199. PMID 11039128. Check date values in:
|date=(help) - ↑ Zinn, A. R.; et al. (1998-12). "Evidence for a Turner syndrome locus or loci at Xp11.2-p22.1". American Journal of Human Genetics. 63 (6): 1757–1766. doi:10.1086/302152. ISSN 0002-9297. PMC 1377648. PMID 9837829. Check date values in:
|date=(help) - ↑ Sävendahl, L.; et al. (2000-10). "Delayed diagnoses of Turner's syndrome: proposed guidelines for change". The Journal of Pediatrics. 137 (4): 455–459. doi:10.1067/mpd.2000.107390. ISSN 0022-3476. PMID 11035820. Check date values in:
|date=(help) - ↑ Kesler, Shelli R. (2007-07). "Turner syndrome". Child and Adolescent Psychiatric Clinics of North America. 16 (3): 709–722. doi:10.1016/j.chc.2007.02.004. ISSN 1056-4993. PMC 2023872. PMID 17562588. Check date values in:
|date=(help) - ↑ Gravholt, Claus H.; et al. (2024-06-05). "Clinical practice guidelines for the care of girls and women with Turner syndrome". European Journal of Endocrinology. 190 (6): G53–G151. doi:10.1093/ejendo/lvae050. ISSN 1479-683X. PMID 38748847 Check
|pmid=value (help). - ↑ Cui, Xiaoxiao; et al. (2018-11). "A basic understanding of Turner syndrome: Incidence, complications, diagnosis, and treatment". Intractable & Rare Diseases Research. 7 (4): 223–228. doi:10.5582/irdr.2017.01056. ISSN 2186-3644. PMC 6290843. PMID 30560013. Check date values in:
|date=(help) - ↑ Nielsen, J.; et al. (1991-05). "Chromosome abnormalities found among 34,910 newborn children: results from a 13-year incidence study in Arhus, Denmark". Human Genetics. 87 (1): 81–83. doi:10.1007/BF01213097. ISSN 0340-6717. PMID 2037286. Check date values in:
|date=(help) - ↑ Urbach, Achia; et al. (2009). "Studying early lethality of 45,XO (Turner's syndrome) embryos using human embryonic stem cells". PloS One. 4 (1): e4175. doi:10.1371/journal.pone.0004175. ISSN 1932-6203. PMC 2613558. PMID 19137066.
- ↑ Gunther, Daniel F.; et al. (2004-09). "Ascertainment bias in Turner syndrome: new insights from girls who were diagnosed incidentally in prenatal life". Pediatrics. 114 (3): 640–644. doi:10.1542/peds.2003-1122-L. ISSN 1098-4275. PMID 15342833. Check date values in:
|date=(help)
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Notes
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