Turner syndrome (45,X)

• Karyotype: 45,X (complete monosomy ~50%)
• Mosaic forms: 45,X/46,XX or 45,X/46,XY
• Structural X abnormalities: isochromosome Xq, ring X, deletions
• Not associated with advanced maternal age (unlike autosomal trisomies)

Genotype-phenotype: which piece of the X is missing

The karyotype is not just a label. What is lost predicts what the patient has.

• Isochromosome Xq (loss of Xp): short stature and the classic somatic features, since SHOX and the rest of Xp are lost. Higher rate of autoimmune thyroid disease
• Xp deletions: short stature with few other features when the deletion is small and distal, because SHOX haploinsufficiency is what drives the height
• Xq deletions: gonadal failure and primary amenorrhea with normal stature, since the ovarian maintenance region sits on Xq
• Ring X, 45,X/46,X,r(X): the important exception to everything else on this page. A small ring that has lost the X-inactivation center (XIST) cannot be inactivated, so genes on the ring are expressed from both the ring and the normal X. The resulting functional disomy produces a phenotype more severe than standard Turner syndrome, including intellectual disability and a syndromic facial appearance. When a ring X is reported, ask the laboratory whether XIST is present and whether the ring is inactivated. That answer, not the presence of the ring, is what predicts cognition

• Short stature (SHOX haploinsufficiency)
• Gonadal dysgenesis → primary amenorrhea, infertility
• Lymphedema in newborns (hands/feet)
• Webbed neck (cystic hygroma remnant)
• Congenital heart defects: bicuspid aortic valve (30%), coarctation of aorta (10%)
• Renal anomalies (horseshoe kidney)
• Normal intelligence (may have visuospatial learning differences). The exception is a small ring X that has lost XIST, which does cause intellectual disability

• Karyotype (increased cell count may be needed to detect mosaicism)
• Prenatal: cystic hygroma, coarctation, hydrops

The differential for primary amenorrhea is organized by presence/absence of breast development and a uterus. Turner sits in the "no breasts, uterus present" cell.

• Noonan syndrome: Turner-like phenotype (short stature, webbed neck, congenital heart disease, lymphedema) but normal karyotype, autosomal dominant PTPN11 and related RAS-MAPK genes, affects both sexes. Historically called "male Turner."
• 45,X/46,XY mixed gonadal dysgenesis: overlapping somatic features but Y-line material present; gonadoblastoma risk and variable genital phenotype.
• Swyer syndrome (46,XY pure gonadal dysgenesis): streak gonads with primary amenorrhea but normal female stature, uterus present (Müllerian structures retained because dysgenetic gonads produce no AMH). High gonadoblastoma risk.
• Androgen insensitivity syndrome (complete AIS): 46,XY, breast development present, uterus absent (AMH suppression). Distinguishes by karyotype and pelvic imaging.
• Müllerian agenesis (MRKH): 46,XX, normal breast development, uterus absent. Ovaries normal, so puberty proceeds normally except for amenorrhea.
• Primary ovarian insufficiency (non-Turner): FMR1 premutation, autoimmune oophoritis, prior chemotherapy/radiation. Normal stature, no syndromic features.

• Growth hormone therapy for short stature
• Estrogen replacement at puberty
• Cardiac surveillance (risk of aortic root dilation/dissection)
• Screen for Y chromosome material (gonadoblastoma risk)