TURNER SYNDROME (GONADAL DYSGENESIS)

Overview

• Definition: Turner syndrome, or X-chromosome monosomy, is a leading consideration in short-stature females with primary amenorrhea.
• Incidence: ~1 in 2500 live-born phenotypic female births.
• Classical Features (described by Turner, 1938):
  • Short stature
  • Webbed neck (pterygium colli)
  • Cubitus valgus (forearm angle)
  • Broad, shield-like chest

Karyotypes

1. 45,X (most common)
2. Mosaic forms (e.g., 45,X/46,XX; 45,X/46,XY)
3. Structural abnormalities of the X chromosome (e.g., deletions, ring chromosome)

• Cause: Typically nondisjunction or chromosome loss during gametogenesis in either parent.
  • ~1/3 retain paternal X; 2/3 retain maternal X.
  • ~25% have mosaicism.

Pathophysiology

• Short Stature:
  • Loss of SHOX gene on the pseudoautosomal region (Xp22) → deficient osteogenic factor → short stature, cubitus valgus, short 4th metacarpals.
• Gonadal Dysgenesis:
  • Rudimentary “streak” gonads → minimal estrogen → sexual infantilism, primary amenorrhea.
  • A small subset with mosaicism may have some pubertal development or cyclical menses.

Clinical Features

1. Height / Body Proportions
   • Nearly all <5 feet tall if untreated.
   • May show increased upper-to-lower body segment ratio (longer torso relative to legs).
2. Neonatal Findings
   • Congenital lymphedema of hands/feet.
   • Cutis laxa (excess neck skin).
3. Skeletal
   • Short, webbed neck
   • High-arched palate
   • Shield chest (broad, widely spaced nipples)
   • Short 4th metacarpals
   • Cubitus valgus
4. Facial/Ear/Neck
   • Micrognathia, “fishmouth” appearance, low-set/deformed ears, posterior hairline extends down the neck.
   • Frequent otitis media (eustachian tube anomalies).
5. Cardiovascular
   • Coarctation of the aorta
   • Bicuspid aortic valve, elongation of transverse aortic arch
   • Hypertension, risk of aortic dissection
6. Renal
   • Horseshoe kidney, ureteropelvic junction anomalies, other structural kidney issues.
7. Neurocognitive
   • Intelligence usually normal, but may have learning disabilities (particularly visuospatial, math).
   • Increased risk of attention-deficit issues, social cognition deficits (e.g., trouble interpreting facial expressions).
8. Endocrine / Metabolic
   • Hypothyroidism (often autoimmune / Hashimoto’s).
   • Glucose intolerance, possible diabetes mellitus.
   • Liver enzyme elevations.
   • Frequent bone fractures, osteoporosis (estrogen deficiency + SHOX haploinsufficiency).
9. Other
   • Frequent keloid formation after surgery.
   • Pigmented nevi, telangiectasias.

Gonadal Findings

• Infantile uterus + fallopian tubes.
• Streak gonads (fibrous tissue instead of functional ovaries).
• Primary amenorrhea and lack of secondary sex characteristics in most.
• Some mosaic variants (45,X/46,XX) may have partial ovarian function → variable breast development, possible scant menses, or even normal cycles.

Variants with Y Mosaicism

• 45,X/46,XY may lead to mixed gonadal dysgenesis → ambiguous genitalia, virilization.
• If a Y chromosome is present, prophylactic gonadectomy is recommended due to high risk of gonadoblastoma or dysgerminoma.

Diagnosis

• Clinical suspicion: Short-stature phenotypic female with lack of normal pubertal development and/or Turner stigmata.
• Karyotype (peripheral blood) confirms 45,X or variants.
• LH, FSH: Elevated from infancy onward (primary ovarian failure).
• Past diagnostic method: Barr body (buccal smear) is now obsolete.

Management

1. Growth Hormone Therapy
   • Begun in childhood when height <5th percentile.
   • Gain of ~2–6 inches in final adult height.
2. Estrogen Replacement
   • Induce secondary sexual development, optimize bone health, cognitive benefits.
   • Typically start at ~age 13–14 with low-dose estrogen, then increment.
   • Add progestin once breakthrough bleeding or full estrogen therapy established to protect endometrium.
3. Cardiovascular Monitoring
   • Regular echocardiography to detect coarctation, aortic root dilation.
   • Blood pressure monitoring.
4. Thyroid
   • Annual TSH measurement due to hypothyroidism risk.
5. Fertility
   • Generally infertile with streak gonads, but some mosaic forms can conceive spontaneously or via assisted reproductive technologies.
6. Psychosocial Support
   • Evaluate and manage learning disabilities, social cognition challenges, and psychological well-being.