Turner's Syndrome

This is a chromosomal disorder (X0) karyotype or mosaic (15%), eg 45X/46,XX or 45,X/47,XXX.), first described by Henry H. Turner in 1938.

1:2500 girls (most common sex-chromosome abnormality in females). Some 15% of spontaneous abortions have the 45X karyotype. The prevalence is similar across different countries.

Turner's syndrome is caused by absence of a set of genes from one short arm of one X chromosome. In the 45X karyotype about two thirds have an absent paternal X chromosome. Advanced maternal age is not a risk factor for Turner's syndrome.

Turner's syndrome can be diagnosed by amniocentesis or chorionic villous sampling which allow karyotyping of the foetus. Initial screening is by ultrasound.¹ Antenatal findings which might prompt use of methods to karyotype the foetus include:

• Nuchal cystic hygroma
• Horseshoe kidney
• Nonimmune foetal hydrops
• Cardiac anomalies (see above)
• Elevated maternal alpha-fetoprotein (AFP) or human chorionic gonadotrophin (HCG).

Classic features are short stature (spontaneous final height is in range 139-147 cm) gonadal dysgenesis (primary and secondary amenorrhoea) and lymphoedema.^2,3

• Newborn infants may be recognised because they are small for dates, have lymphoedema of hands and feet and excessive skin at nape of neck
• Older children have: short stature (98%); gonadal dysgenesis (95%); high palate (82%); short neck with low hairline (80%); hypoplastic and widely-spaced nipples (78%); broad chest, wide carrying angle (cubitus valgus); hyperconvex nails(75%); lymphoedema; prominent anomalous ears; excessive naevi and telangiectasia(70%).
• Dysmorphic Features:
  • Eyes - downslanting, wide epicanthic folds, ptosis and strabismus. Ptosis, nystagmus, cataracts, amblyopia, and myopia may develop.
  • Ears - prominent upturned lobules. Deafness may develop secondary to chronic otitis media (80%); but 50-70% have a sensorineural hearing impairment.
  • Mouth - high palate and mandible abnormalities can result in crowding of teeth and malocclusion
  • Neck - short, webbed, low hairline
  • Chest - broad (scutiform thorax), pectus excavatum, inverted, hypoplastic, widely-spaced nipples
  • Joints - cubitus valgus (>15%), congenital hip dislocation (5-10%)
  • Hands - short fingers, forearm and carpal developmental abnormalities, nail hypoplasia - small convex or concave upturned nails
  • Skin lymphoedema - hands, feet, neck (pterygium coli), pigmented naevi, vitiligo, keloid, seborrheic dermatitis; increased body hair with alopecia.
• Cardiovascular - Heart malformations (20-30%) - Coarctation of the aorta (15-30%), bicuspid aortic valve (33%), aortic aneurysms, mitral valve prolapse (25%), ectopia cordis, hypoplastic left heart, pulmonary stenosis. Vascular malformations: (generalized vascular dysplasia, intestinal telangiectasias, haemangiomas, venous ectasias, lymphangiectasia etc), cystic hygroma, multiple renal arteries (90%). Conduction defects including prolonged QT interval.⁴
• Genitourinary Anomalies (33-60%) eg double collecting system, absent kidney, malrotation, horseshoe kidneys (10%) and 6-10% have silent hydronephrosis.
• Gonadal Dysgenesis/Failure - many have fibrotic ovarian streaks at time of birth (removal of bilateral streak gonads prior to starting school is recommended in 45,XO/46,XY mosaics). Spontaneous puberty occurs in 5-15% of cases so unassisted fertility is theoretically possible.
• There is a risk of keloid formation with surgery

• Chromosome analysis, TFT, thyroid antibodies, skeletal survey (changes in hands, feet, knees, spine, ribs, pelvis, skull and delayed bone growth)
• ECG, echocardiogram
• Renal ultrasound screening is recommended every 10 years for silent hydronephrosis
• Screen regularly to detect impaired serum glucose tolerance and hypertension

Note that the buccal smear for Barr bodies is no longer used.

Crohn's Disease⁵, Coeliac disease,⁶ Hashimoto's thyroiditis,⁷ malignant glioblastomas, gonadoblastomas,⁸ hypertension⁹ and diabetes mellitus are all associated with Turner's Syndrome.

Turner's Syndrome is obviously a lifelong condition and although the majority of patients are healthy they are susceptible to a number of chronic conditions. For this reason multidisciplinary¹⁰ follow-up is required as an exercise in screening and prevention as well as treatment where necessary.^11,10 Cardiac defects are likely to be the most significant associated health problems.¹² The need for long term surveillance and awareness of associated conditions should be promoted. Problems of most concern to patients may vary with age but the main four concerns revolve around growth, puberty, fertility and general health.
Shared care should include:

• Paediatrics and paediatric endocrinology. Particular attention should be given to growth, pubertal development, thyroid function, screening for Coeliac disease⁶ and prevention of osteoporosis.
• Ophthalmology. Screening for amblyopia and other associated eye disorders is recommended.
• ENT. Screening for deafness and secretory otitis media is appropriate.
• Dentist. Problems with crowding of teeth and malocclusion should be addressed. Antibiotic prophylaxis to prevent subacute bacterial endocarditis is likely to be necessary.
• Orthopedics. Regular review is usually unnecessary.
• Cardiology. All patients should have a cardiological evaluation including echocardiography. Some repeat this every 5 years. Regular imaging every 2 years has been suggested as has use of MRI.¹³
• Urology. About 30% of patients have renal anomalies. There is an increased risk of Wilm's tumour. Annual urea and electrolytes, creatinine and urine culture is recommended.
• Genetic counselling. It should be emphasised that Turner's Syndrome is not inherited.
• Psychological support. Generally psychological health is good but educational and social assessments and support may help integration and general wellbeing.¹⁴ There is some evidence for lower than average levels of neuroticism and a tendency to be more extrovert.¹⁵ There are also studies that show increased levels of hyperactivity and inattention.¹⁶
• Somatropin (human growth hormone) adds a median of 5.1cm to final stature.¹⁷ Gonadal Failure is treated with combined oestrogen and progesterone (begin at time appropriate for teenage peers¹⁸),initially low dose oestrogen for 1-2 years then progress to larger doses cycled with progesterone and then maintain with the combined oral contraceptive.¹⁹ Fertility may be achieved with oocyte donation, gamete or embryo transplantation.

Generally the prognosis is good. Patients are usually shorter than average and almost all are infertile (although assisted fertility is successful). Patients are not mentally impaired (although some aspects of brain function may be affected²⁰) and life expectancy is only slightly reduced.

A review of patients with Turner's Syndrome may reveal a previously unmet need for regular screening as above.