GTS5:Turner syndrome

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Primary Author(s)*

Kathleen Bone, PhD (EXAMPLE: Jane Smith, PhD)

WHO Classification of Disease

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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. 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.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. 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. However, TS is among the most common chromosomal disorders, affecting 1–2% of conceptions, with approximately 99% of affected pregnancies resulting in loss. The true prevalence of TS is difficult to determine, as many individuals remain undiagnosed or are only diagnosed later in adulthood.

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

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Notes

*Primary authors will typically be those that initially create and complete the content of a page.  If a subsequent user modifies the content and feels the effort put forth is of high enough significance to warrant listing in the authorship section, please contact the Associate Editor or other CCGA representative.  When pages have a major update by a new author, the new author will be acknowledged at the beginning of the page, and those who contributed previously will be acknowledged below as a prior author.  Additional global feedback or concerns are also welcome.

Prior Author(s):