Description

• Turner syndrome (TS) is a condition characterized by ovarian dysgenesis and short stature in phenotypic females who have only one sex chromosome, an X, although a partial second sex chromosome, X or Y, may be present.
• The most common sex chromosome abnormality syndrome in females
• System(s) affected: cardiovascular; reproductive; endocrine/metabolic; musculoskeletal; nervous; renal/urologic
• Synonym(s): Ullrich-Turner syndrome; Bonnevie-Ullrich syndrome; monosomy X; sexual infantilism; gonadal dysgenesis

Epidemiology

Incidence

• Occurs in 1/2,500 live female births
• ~1–3% of all conceptuses affected, of whom <1% will survive to term; accounts for 15% of all spontaneously aborted fetuses
• Predominant sex: female only

Prevalence
Estimated 50,000 to 75,000 females in the United States

Etiology and Pathophysiology

• Haploinsufficiency of short stature homeobox-containing gene (SHOX), located in the pseudoautosomal region of the X chromosome, is thought to be responsible for short stature and skeletal abnormalities in TS.
• Monosomy for all or part of the X chromosome can result in features of TS; genes located mainly in Xp11.2–p22.1

Genetics

• 50% of patients have 45,X karyotype (sporadic nondisjunction). Translocations involving the X chromosome may result in TS.
• 80% of girls with 45,X have maternal X, although phenotype is identical if X is paternal.
• TS occurs with a deletion of the SRY segment of the Y chromosome in 46,XY karyotype, with resulting female phenotype (5–6%).
• FISH or PCR may be necessary to identify Y material because of increased risk of gonadoblastoma (7–10%) if Y material is present; indicated if signs of virilization or marker chromosome present
• Also may be mosaic for 45,X/46,XY, 45,X/46,XX, or 45,X/47,XXX

Commonly Associated Conditions

• Gonadal dysgenesis (infertility 98%)
• Short stature (100%), usually not growth hormone (GH)-deficient. Height is generally 20 cm below that expected for family.
• Hearing loss (50%), otitis media (70–100%)
• Frequent (>5–10% but <50% of individuals)
  • Cardiovascular abnormalities, including coarctation of the aorta (15–30%), aortic valvular disease (1/3 have bicuspid aortic valve), mitral valve prolapse (25%), aortic root dilatation (8–29%), aortic dissection, electrocardiogram (ECG) abnormalities
  • Bicuspid aortic valve or left-sided obstructive lesion in a female fetus or child should prompt a genetic evaluation for TS (1)[C].
  • Renal abnormalities
  • Hypertension (HTN; >30%)
  • Glucose intolerance
  • Hyperlipidemia
  • Ocular abnormalities
  • Hypothyroidism, autoimmune thyroiditis
  • GI vascular malformations
  • Glucose intolerance
  • Gonadoblastoma in 8% of individuals with Y chromosomal material
• Occasional: inflammatory bowel disease, celiac disease, colon cancer, neuroblastoma, juvenile rheumatoid arthritis, liver disease (especially cirrhosis)