Turner's syndrome is caused by absence of a set of genes from one short arm of one X chromosome:

• It may be due to absence of one X chromosome, the 45X or (X0) karyotype. About two thirds have an absent paternal X chromosome.
• Approximately 15% are mosaics, 45X/46,XX or 45,X/47,XXX.

The classical features of Turner's syndrome are:

• Short stature; spontaneous final height is in the range of 139-147 cm.
• Gonadal dysgenesis; primary and secondary amenorrhoea.
• Lymphoedema.^1,2

It was first described by Henry H. Turner in 1938.

Epidemiology

It is the most common sex-chromosome abnormality in females with a prevalence of 1 in 2,500. 15% of spontaneous abortions have the 45X karyotype. The prevalence is similar across different countries.

NB: advanced maternal age is not a risk factor for Turner's syndrome.

Clinical features

• Newborn infants may be recognised because they are small for dates, have lymphoedema of the hands and feet and excessive skin at the nape of the 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%); however, 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, seborrhoeic dermatitis; increased body hair with alopecia.
• Cardiovascular problems:³
  • Heart malformations (20-30%).
  • Coarctation of the aorta (15-30%).
  • Bicuspid aortic valve (33%).^4,5
  • Aortic aneurysms.⁴
  • Mitral valve prolapse (25%).
  • Ectopia cordis.
  • Hypoplastic left heart.
  • Pulmonary stenosis.
  • Vascular malformations (including generalised vascular dysplasia, intestinal telangiectasias, haemangiomas, venous ectasias, lymphangiectasia, cystic hygroma and multiple renal arteries (90%)).
  • Conduction defects including prolonged QT interval.⁶
• Genitourinary anomalies (33-60%):
  • Double collecting system.
  • Absent kidney.
  • Malrotation.
  • Horseshoe kidneys (10%).
  • Silent hydronephrosis (6-10%).
• 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.

Investigations

• 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.

Associated diseases

• Crohn's disease⁸
• Coeliac disease⁹
• Hashimoto's thyroiditis¹⁰
• Malignant glioblastomas
• Gonadoblastomas¹¹
• Hypertension¹²
• Diabetes mellitus¹³

Prenatal diagnosis

Initial screening is by ultrasound.¹⁴ It can be diagnosed by amniocentesis or chorionic villous sampling which allow karyotyping of the fetus. Antenatal findings which might prompt use of methods to karyotype the fetus include:

• Nuchal cystic hygroma.
• Horseshoe kidney.
• Nonimmune fetal hydrops.
• Cardiac anomalies (see above, under 'Clinical features').
• Elevated maternal alpha-fetoprotein (AFP) or human chorionic gonadotrophin (hCG).

Management

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 multidisciplinary follow-up is required as an exercise in screening and prevention as well as treatment where necessary.^15,16

Cardiac defects are likely to be the most significant associated health problems.¹⁷ The need for long-term surveillance and awareness of associated conditions should be promoted. Regular renal ultrasound, and screening for impaired glucose tolerance and hypertension are recommended.

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 disease⁹ and prevention of osteoporosis.
• Ophthalmology. Screening for amblyopia and other associated eye disorders is recommended.
• Ear, nose and throat (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 now less likely to be necessary (see separate article Prevention of Endocarditis).
• Orthopaedics. 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.¹⁸
• Urology. About 30% of patients have renal anomalies. There is an increased risk of Wilms' tumour. Annual U&Es, creatinine and urine culture are 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.¹⁹ There is some evidence for lower-than-average levels of neuroticism and a tendency to be more extrovert.²⁰ There are also studies that show increased levels of hyperactivity and inattention.²¹
• Somatropin (human growth hormone) adds a median of 5.1 cm to final stature.^22,23 Gonadal failure is treated with combined oestrogen and progesterone (begin at a time appropriate for teenage peers),²⁴ initially low-dose oestrogen for 1-2 years, then progress to larger doses cycled with progesterone and then maintain with the combined oral contraceptive.²⁵ Fertility may be achieved with oocyte donation, gamete or embryo transplantation.

Prognosis

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 affected) and life expectancy is only slightly reduced.²⁶

Document references

1. Guarneri MP, Abusrewil SA, Bernasconi S, et al; Turner's syndrome. J Pediatr Endocrinol Metab. 2001 Jul;14 Suppl 2:959-65. [abstract]
2. Turner Syndrome Society of the United States; Home page
3. Sybert VP; Cardiovascular malformations and complications in Turner syndrome. Pediatrics. 1998 Jan;101(1):E11. [abstract]
4. Lopez L, Arheart KL, Colan SD, et al; Turner syndrome is an independent risk factor for aortic dilation in the young. Pediatrics. 2008 Jun;121(6):e1622-7. Epub 2008 May 26. [abstract]
5. Sachdev V, Matura LA, Sidenko S, et al; Aortic valve disease in Turner syndrome. J Am Coll Cardiol. 2008 May 13;51(19):1904-9. [abstract]
6. Bondy CA, Van PL, Bakalov VK, et al; Prolongation of the cardiac QTc interval in Turner syndrome. Medicine (Baltimore). 2006 Mar;85(2):75-81. [abstract]
7. Grote FK, Oostdijk W, De Muinck Keizer-Schrama SM, et al; The diagnostic work up of growth failure in secondary health care; an evaluation of consensus guidelines. BMC Pediatr. 2008 May 13;8(1):21. [abstract]
8. Scammell AM; Juvenile onset inflammatory bowel disease. Is more common in people with Turner's syndrome. BMJ. 1994 Sep 3;309(6954):606.
9. Sagodi L, Solyom E, Tamasi K, et al; Prevalence of coeliac disease in Turner syndrome. Orv Hetil. 2006 Jun 25;147(25):1185-8. [abstract]
10. Livadas S, Xekouki P, Fouka F, et al; Prevalence of thyroid dysfunction in Turner's syndrome: a long-term follow-up study and brief literature review. Thyroid. 2005 Sep;15(9):1061-6. [abstract]
11. Lipay MV, Bianco B, Verreschi IT; Gonadal dysgenesis and tumors: genetic and clinical features.Arq Bras Endocrinol Metabol. 2005 Feb;49(1):60-70. Epub 2006 Mar 16. [abstract]
12. Gravholt CH, Hansen KW, Erlandsen M, et al; Nocturnal hypertension and impaired sympathovagal tone in Turner syndrome. J Hypertens. 2006 Feb;24(2):353-60. [abstract]
13. Lichiardopol C, Mota M, Braicu D, et al; Diabetes mellitus and Turner syndrome. Rom J Intern Med. 2007;45(3):299-304. [abstract]
14. Papp C, Beke A, Mezei G, et al; Prenatal diagnosis of Turner syndrome: report on 69 cases. J Ultrasound Med. 2006 Jun;25(6):711-7; quiz 718-20. [abstract]
15. Donaldson MD, Gault EJ, Tan KW, et al; Optimising management in Turner syndrome: from infancy to adult transfer. Arch Dis Child. 2006 Jun;91(6):513-20. [abstract]
16. Snajderova M, Heresova J, Mardesic T, et al; Turner syndrome: overview of problems, present status, proposals for care and a protocol for monitoring in childhood, adolescence and adulthood. Cas Lek Cesk. 2001 Aug 30;140(17):533-7. [abstract]
17. Kavoussi SK, Christman GM, Smith YR; Healthcare for adolescents with turner syndrome. J Pediatr Adolesc Gynecol. 2006 Aug;19(4):257-65. [abstract]
18. Ilyas M, Chu C, Ettles D, et al; Evaluation by magnetic resonance imaging of aortic dilatation and coarctation in adult Turner syndrome patients. Clin Endocrinol (Oxf). 2006 Aug;65(2):154-7. [abstract]
19. Kilic BG, Ergur AT, Ocal G; Depression, levels of anxiety and self-concept in girls with Turner's syndrome. J Pediatr Endocrinol Metab. 2005 Nov;18(11):1111-7. [abstract]
20. Boman UW, Hanson C, Hjelmquist E, et al; Personality traits in women with Turner syndrome. Scand J Psychol. 2006 Jun;47(3):219-23. [abstract]
21. Russell HF, Wallis D, Mazzocco MM, et al; Increased Prevalence of ADHD in Turner Syndrome with No Evidence of Imprinting Effects. J Pediatr Psychol. 2006 Mar 8. [abstract]
22. Bramswig JH; Long-term results of growth hormone therapy in Turner syndrome. Endocrine. 2001 Jun;15(1):5-13. [abstract]
23. Ramos AV, Silva IN, Goulart EM; Turner syndrome: searching for better outcomes. Clinics. 2008 Apr;63(2):173-8. [abstract]
24. Davenport ML; Evidence for early initiation of growth hormone and transdermal estradiol therapies in girls with Turner syndrome. Growth Horm IGF Res. 2006 Jul;16 Suppl A:S91-7. Epub 2006 Jun 2. [abstract]
25. Elsheikh M, Hodgson HJ, Wass JA, et al; Hormone replacement therapy may improve hepatic function in women with Turner's syndrome. Clin Endocrinol (Oxf). 2001 Aug;55(2):227-31. [abstract]
26. Holzapfel M, Barnea-Goraly N, Eckert MA, et al; Selective alterations of white matter associated with visuospatial and sensorimotor dysfunction in turner syndrome. J Neurosci. 2006 Jun 28;26(26):7007-13. [abstract]

Internet and further reading

• Takeda A, Cooper K, Bird A, et al; Recombinant human growth hormone for the treatment of growth disorders in Health Technol Assess. 2010 Sep;14(42):1-209, iii-iv. [abstract]

Acknowledgements