Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2009) 19 P189

SFEBES2009 Poster Presentations Endocrine tumours and neoplasia (32 abstracts)

Genetics in mainstream medicine: best practice review

S Stewart 1,2 , J Watkinson 2 , J Franklyn 2 , E Woodward 1 & T Cole 1,2

1West Midlands Regional Clinical Genetics Unit, Birmingham Women’s Health Care Trust, Birmingham, West Midlands, UK; 2University Hospital Birmingham NHS Trust, Birmingham, West Midlands, UK.

Medullary thyroid cancer (MTC) is rare and mainly sporadic. About ≤25% of cases are inherited from a Ret protooncogene (RET) mutation. >90% of positive mutations develop MTC, either as familial (FMTC), or as part of MEN2. Early detection and treatment of MTC with total thyroidectomy improves prognosis.

In 2006, as part of a project to deliver genetics into mainstream medicine, a multidisciplinary clinic (MDC) comprising a specialist thyroid surgeon, endocrinologist, clinical geneticist and endocrine genetic nurse specialist was initiated.

Existing/new MTC patients were referred to this clinic, detailed family history taken and counselling given prior to diagnostic DNA screening.

From 19* predictive tests, 16 were negative for a RET mutation, confirming sporadic MTC.

Three significant RET mutations were found (*reconfirmed in one patient- mutation originally detected elsewhere; 15.8% of those tested).

Family A −p.C618S, Family B −p.Val 804M and Family C −p.Val 804M (reconfirmed homozygous).

Mutation positive patients underwent further counselling and investigations for features of MEN2 with information provided for relevant relatives.

Cascade testing of relatives has so far generated 21 predictive tests: 14 positive (including two obligatory heterozygotes) and 6 negative results. (1 result outstanding) Testing elsewhere confirmed another positive result (c.2410G>A Val 804M).

All relatives, except one with palpable goitre, had no symptoms or signs of thyroid disease at testing. 11/14 RET mutation carriers elected for prophylactic thyroidectomy. Histology revealed MTC in 6, C cell hyperplasia in 5, with 1 patient currently awaiting surgery. There are 2 RET mutation carriers aged <3 years at screening, with surgery ≤5 years of age. MEN2 screening initiated for all patients is currently normal.

The joint MDC leads to an increased early detection and treatment of this rare thyroid cancer in asymptomatic individuals at high risk of disease. Furthermore, we have identified two families with the rare p.Val 804M mutation.

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