Turners syndrome

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"Turner syndrome"[MeSH Terms] AND management

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Turner Syndrome

Fig. 4.20 - Clinical features and karyotypes of Turner syndrome (Robbins & Kumar Basic Pathology)

Definition

Turner syndrome is characterized by primary hypogonadism in phenotypic females, resulting from complete or partial monosomy of the X chromosome. It is the most common sex chromosome abnormality in females.

Incidence: approximately 1 in 2,000-3,000 live-born females
Only ~1% of monosomy X embryos survive to birth; the 45,X karyotype accounts for ~18% of all chromosomally abnormal spontaneous abortions

Karyotypes

Type	Karyotype	Frequency
Classic	45,X	~57%
Isochromosome of long arm	46,X,i(Xq10) - loss of short arm	Most common structural variant
Ring chromosome	46,X,r(X) - deletion of both long and short arm portions	Less common
Short/long arm deletion	46,X,del(Xp) or 46,X,del(Xq)	Less common
Mosaic	45,X/46,XX; 45,X/46,XY; 45,X/47,XXX	~29%

Key point: 5-10% of patients have Y chromosome sequences (e.g., 45,X/46,XY). These patients carry a significantly elevated risk of gonadoblastoma and require prophylactic gonadectomy.

The true prevalence of mosaicism may be as high as 75% when more sensitive techniques are used. Patients with a higher proportion of 45,X cells have a more severe phenotype; those with detectable 45,X/46,XX mosaicism may appear nearly normal and present only with primary amenorrhea.

Pathogenesis

In ~80% of cases, the X chromosome retained is maternal in origin, implying an error in paternal gametogenesis (absent or defective sperm contributes most errors).
The fetal ovaries develop normally up to ~18 weeks of gestation, but the absence of the second X leads to accelerated oocyte attrition, complete by age 2 years - effectively "menopause before menarche."
SHOX gene (at Xp22.33, pseudoautosomal region, escapes X inactivation): haploinsufficiency of SHOX is responsible for short stature. Normally, both males and females have two copies. SHOX is expressed in the growth plates of long bones (radius, ulna, tibia, fibula).
Genes on the short arm largely determine somatic features; genes on the long arm influence fertility and menstruation.

Clinical Features

At Birth / Infancy

Peripheral lymphedema of dorsum of hands and feet (due to lymph stasis)
Cystic hygroma - markedly distended lymphatic channels at the nape of neck, later manifests as neck webbing
Congenital heart disease in 25-50% of patients

Somatic Features (Childhood onward)

Short stature (below 3rd percentile) - most consistent feature
Webbed neck (pterygium colli) with low posterior hairline
Shield chest with broad thorax and widely spaced nipples
Cubitus valgus (increased carrying angle of the arms)
High-arched palate
Pigmented nevi
Horseshoe kidney

Cardiovascular (most common cause of death in childhood)

Preductal coarctation of the aorta (most common cardiac lesion)
Bicuspid aortic valve
Aortic root dilation in ~30% of cases
100-fold increased risk of aortic dissection
~5% of young females initially diagnosed with coarctation of the aorta have Turner syndrome

Reproductive / Endocrine (Adolescence/Adulthood)

Primary amenorrhea (most common presenting complaint in adults)
Failure to develop secondary sexual characteristics at puberty
Infantile external genitalia, minimal breast development, sparse pubic hair
Streak ovaries - bilateral fibrous white strands devoid of follicles and ova (result of oocyte attrition)
Infertility (a very small number of mosaic patients can conceive)

Other Systemic Associations

Autoimmune hypothyroidism - antithyroid autoantibodies are common; up to 50% of patients (especially those with isochromosome Xp) develop clinical hypothyroidism
Glucose intolerance, insulin resistance, obesity, non-alcoholic fatty liver disease - a subset develops full metabolic syndrome
Subtle deficits in visuospatial information processing - overall intellect is generally within normal limits
Sensorineural hearing loss (noted in ENT literature)

Diagnosis

Short stature + primary amenorrhea in an adolescent/adult female - strong clinical suspicion
Karyotype (peripheral blood lymphocytes) - confirmatory
Prenatal: detected on maternal serum screening (elevated hCG, low estriol) or fetal ultrasound (cystic hygroma, nuchal translucency, hydrops, cardiac defects)
FISH or array CGH for detecting mosaicism or structural rearrangements with Y material

Management

Problem	Treatment
Short stature	Recombinant growth hormone (GH) therapy (started early in childhood); note: GH worsens insulin resistance
Hypogonadism / puberty induction	Estrogen replacement (low-dose estrogen at ~12-13 years, then cyclical estrogen/progesterone)
Fertility	Not typically achievable without donor oocytes + IVF
Cardiovascular	Echocardiography screening; surgical correction of coarctation; aortic surveillance (MRI)
Hypothyroidism	Levothyroxine supplementation
Y-chromosome material	Prophylactic gonadectomy to prevent gonadoblastoma
Psychological	Support for identity, peer relationships, and body image issues

Recent Evidence (2025)

Recent systematic reviews add important updates:

A 2025 meta-analysis (PMID 40557696) confirms the impact of karyotype on congenital heart disease risk in Turner syndrome - structural variants carry different CHD profiles than classic 45,X.
A 2025 meta-analysis (PMID 41243107) quantifies the global prevalence of autoimmune diseases in Turner syndrome, underscoring the need for systematic autoimmune surveillance.
A 2025 systematic review (PMID 39743222) on karyotype-phenotype associations in non-mosaic X chromosome structural rearrangements helps predict clinical severity.

Sources: Robbins & Kumar Basic Pathology; Robbins, Cotran & Kumar Pathologic Basis of Disease; The Developing Human - Clinically Oriented Embryology

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