Turner syndrome — formative SAQs

SAQ 1 (10 marks)

A 13-year-old girl is referred for short stature and absent breast development. She is on the first centile for height, with a low posterior hairline, neck webbing, cubitus valgus, and a soft left infraclavicular murmur. Her bone age is delayed. FSH is markedly elevated and oestradiol is low. A peripheral blood karyotype returns 45,X. [2] [1]

a) Explain the pathophysiology underlying her short stature and skeletal features, naming the specific gene responsible and its chromosomal location. (2 marks) [2]

b) Outline the baseline investigations you will arrange now that the karyotype is confirmed, naming the cardiovascular imaging that defines the aortic risk and two further organ systems requiring screening. (3 marks) [1] [8]

c) Describe the growth-hormone and oestrogen-replacement plan, including the rationale for the timing of each and the approximate adult-height gain expected from growth hormone. (3 marks) [3] [1]

d) Explain why the aortic dissection surveillance thresholds are lower in Turner syndrome than in the general population, and name two clinical features that heighten the dissection risk. (2 marks) [1] [8]

SAQ 2 (10 marks)

A karyotype sent for a 4-year-old girl with short stature returns 45,X/46,XY mosaicism. The parents are anxious about the result and have read online about cancer risk. [1] [8]

a) Explain the gonadoblastoma risk in this karyotype and the management action it mandates. (3 marks) [1] [8]

b) Contrast this karyotype with 45,X/46,XX mosaicism in terms of phenotype severity, likelihood of spontaneous puberty, and surveillance requirements. (3 marks) [2] [1]

c) Describe how you would counsel the parents, addressing their anxiety, the cancer risk, the future reproductive implications, and the psychosocial support. (2 marks) [1]

d) Outline the structured transition plan from paediatric to adult care for a girl with Turner syndrome, naming the two non-negotiable surveillance elements that must transfer. (2 marks) [8]

Marking guide

SAQ 1. Her short stature and skeletal features (cubitus valgus, short fourth metacarpals, high-arched palate, Madelung deformity) are driven by haploinsufficiency of the SHOX (short-stature homeobox) gene, located in the pseudoautosomal region of Xp, which escapes X-inactivation and governs chondrocyte proliferation in the growth plate. Baseline investigations: echocardiography and cardiac MRI to define bicuspid aortic valve, coarctation, and aortic dimensions; renal ultrasound (horseshoe kidney, collecting system anomalies); audiology (conductive and sensorineural loss); thyroid function and antibodies (autoimmune hypothyroidism); bone age and pelvic ultrasound; fasting glucose and lipids. Growth hormone should be started early (four to six years) and continued to near-final height, with the Canadian randomised trial showing approximately 5 to 7 cm adult-height gain; oestrogen induction begins at about 11 to 12 years at low dose, titrated over two to three years, with progestogen added for endometrial protection and uterine priming. The Turner aorta is intrinsically abnormal with intimal thickening and dilation, so it dissects at smaller dimensions than the general-population aorta, and prophylactic surgery thresholds are lower; risk-heightening features include bicuspid aortic valve, coarctation, and hypertension. [1] [2] [3] [8]

SAQ 2. The 45,X/46,XY mosaic carries a materially elevated risk of gonadoblastoma (a carcinoma in situ) in the dysgenetic Y-bearing streak gonad, so the guideline action is prophylactic gonadectomy once the diagnosis is confirmed, with surveillance for residual gonadal tissue. By contrast, 45,X/46,XX mosaicism is generally milder — stature may be less compromised, spontaneous puberty and menarche may occur, and a minority achieve spontaneous pregnancy — but the surveillance is unchanged because the aortic, thyroid, renal, and audiology risks persist. Counselling should address the parents' anxiety directly and honestly, explain that the cancer risk is the reason for the gonadectomy (which removes it), outline the future need for oestrogen replacement regardless, and offer psychosocial and genetic-counselling support. The structured transition requires a named adult endocrinologist and cardiologist, a reconciled written summary, and explicit transfer of the aortic imaging and oestrogen and bone-density surveillance — the two non-negotiable elements. [1] [2] [8]