Key Facts

Turner syndrome is the most common sex chromosome abnormality in females. It results from the complete or partial loss of one X chromosome and affects multiple organ systems.

Epidemiology

• Incidence: 1 in 2,000-2,500 live female births
• No association with maternal age (unlike Down syndrome)
• 99% of 45,X conceptions spontaneously abort (accounts for ~10% of all miscarriages)

Aetiology

• 45,X (complete monosomy X): ~50% of cases
• Mosaicism (45,X/46,XX): ~25% – often milder phenotype
• Structural X abnormalities: isochromosome Xq, ring X, Xp deletions
• Y chromosome material: present in ~5% – increased risk of gonadoblastoma
• Paternal X is lost in ~80% of cases (maternal X retained)

Pathophysiology

• Loss of SHOX gene (short stature homeobox) on Xp → short stature
• Loss of genes on Xq → gonadal dysgenesis (accelerated oocyte loss)
• Lymphatic dysfunction in utero → cystic hygroma, webbed neck, peripheral lymphoedema
• Haploinsufficiency of X-linked genes → multisystem effects

Neonatal

• Lymphoedema of hands and feet
• Redundant nuchal skin (from in-utero cystic hygroma)
• Low birth weight, feeding difficulties
• Congenital heart defects detected on newborn screening

Childhood

• Short stature – becomes apparent from age 2-3, progressive growth failure
• Delayed puberty or absent pubertal development
• Recurrent otitis media and hearing loss
• Learning difficulties (non-verbal, visuospatial – verbal IQ typically normal)

Classic Physical Features

• Webbed neck (pterygium colli)
• Shield chest with widely spaced nipples
• Cubitus valgus (increased carrying angle)
• Low posterior hairline
• Multiple naevi
• High-arched palate
• Short 4th metacarpal

Cardiac

• Bicuspid aortic valve (30-50%)
• Coarctation of the aorta (10-20%)
• Aortic root dilatation and risk of dissection (especially in pregnancy)
• Hypertension (common even in childhood)

Red Flags

• Acute chest/back pain → consider aortic dissection (particularly in pregnancy or with bicuspid aortic valve)
• Absent puberty by age 13 → needs endocrine assessment
• Rapid virilisation if Y chromosome material present → gonadoblastoma risk

Bedside

• Accurate height measurement and growth chart plotting
• Blood pressure in all four limbs
• Assessment of pubertal staging (Tanner)

Bloods

• Karyotype: diagnostic – 45,X or mosaic/structural variants
• FSH/LH: elevated (hypergonadotrophic hypogonadism) – particularly from age 10+
• Oestradiol: low
• TFTs: annual screening for autoimmune hypothyroidism
• Coeliac screen: tTG antibodies (increased prevalence)
• Fasting glucose/HbA1c: screen for impaired glucose tolerance
• Liver function: abnormalities common
• IGF-1: before starting GH therapy

Imaging

• Echocardiography: at diagnosis and regularly – bicuspid aortic valve, coarctation, aortic root dimensions
• Cardiac MRI: baseline and every 5-10 years to monitor aortic dimensions
• Renal ultrasound: horseshoe kidney, duplex collecting system (30-40%)
• Pelvic ultrasound: assess uterine size and ovarian morphology
• Bone age X-ray (left wrist): typically delayed

Special Tests

• Audiometry: baseline and regular monitoring (sensorineural and conductive loss)
• DEXA scan: assess bone density from adolescence
• FISH for Y chromosome material: if karyotype suggests – prophylactic gonadectomy if Y material present

Non-pharmacological

• Multidisciplinary team approach: paediatric endocrinology, cardiology, ENT, psychology
• Regular monitoring of growth, cardiac, renal, hepatic, thyroid function
• Educational support (visuospatial/non-verbal learning difficulties)
• Psychological support, peer support groups (Turner Syndrome Support Society UK)

Pharmacological

Growth:

• Somatropin (recombinant growth hormone): 0.045-0.050 mg/kg/day SC
• Started when height falls below 2nd centile or height velocity decreasing
• Continued until near-final height (bone age >14 years, growth velocity <2cm/year)
• Can increase final height by 5-8cm on average
• Consider oxandrolone 0.05mg/kg/day as adjunct in selected patients >9 years

Puberty induction:

• Oestrogen replacement starting age 11-12 (or when clinically appropriate)
• Low-dose ethinylestradiol (2 mcg daily) or transdermal oestradiol patches (6.25-12.5 mcg)
• Gradually increase dose over 2-3 years
• Add cyclical progesterone (medroxyprogesterone 5-10mg for 12-14 days/month) once breakthrough bleeding occurs or after 2 years of oestrogen
• Continue HRT through adult life for bone, cardiovascular, and cognitive health

Other:

• Levothyroxine if hypothyroid
• Antihypertensives if required (beta-blockers to protect aorta)
• Vitamin D and calcium supplementation

Surgical/Interventional

• Prophylactic gonadectomy if Y chromosome material detected
• Cardiac surgery for coarctation or significant aortic valve disease
• Assisted reproduction: egg donation + IVF possible (requires thorough cardiac assessment pre-pregnancy)

Referral Criteria

• All patients need specialist paediatric/adult endocrinology follow-up
• Cardiology review at diagnosis and ongoing
• Pre-pregnancy cardiac MRI and multidisciplinary assessment essential

• Life expectancy reduced by approximately 10-13 years compared to general population
• Cardiovascular disease (including aortic dissection) is the leading cause of premature death
• Risk of aortic dissection: 40 per 100,000 Turner syndrome years (100x general population)
• 95% of women with Turner syndrome are infertile; spontaneous pregnancy occurs in ~2-5% (usually mosaic)
• Intellectual disability is uncommon; specific learning difficulties in visuospatial tasks
• Quality of life can be good with appropriate multidisciplinary care

Monitoring Schedule

Key Associated Conditions