MEN 2 syndromes are autosomal dominant, although with variable penetrance particularly in MEN 2A. This can mean that the age of developing MTC in untreated family members who have the RET mutation can vary widely. Autosomal dominance means that statistically 50 % of children of a family member with the RET mutation will also have MEN 2.

MEN2A is more prevalent than MEN2B, and in children almost exclusively presents as a genetic diagnosis following investigation of the kindred of an adult index case of MTC. More recently children are also being identified by screening children with Hirschprung’s disease, since Hirschprung’s is sometimes be caused by the same the RET mutation as MEN 2A [10, 11]. Ninety seven percent of individuals with MEN2A have a germline mutation of the RET oncogene [12, 13]. Historically families were screened for the development of early MTC using calcitonin screening, but this is unreliable [14], and outcome studies have shown that this approach results in late diagnosis and ineffective prophylactic thyroidectomy. With appropiate genetic testing of children identified as being at risk within an MEN 2A family it is possible to select children with the RET mutation who will have more-or-less a 100 % future risk of MTC development [15]. Current advice is that these children should undergo prophylactic total thyroidectomy before the fifth birthday, since pathological specimens after this age sometimes show that small foci of MTC have already developed. Even by age 5 most show significant C-cell hyperplasia. Rarely MEN2A children have been reported as developing MTC as early as age 3, and it is increasingly possible to stratify patients by genotype to select children who are at risk of earlier MTC development [16]. These children should be offered earlier thyroidectomy. There is still no unequivocal evidence to show that prophylactic thyroidectomy confers a survival advantage in MEN2A, but since complete resection is the only curative option for MTC it is impossible to argue against the logic of carrying out prophylactic surgery before MTC has developed, at least until there is evidence to the contrary.

Children with MEN2B develop MTC much earlier, often by age 1 year [6]. However only 5 % are identified as a result of kindred testing. The typical facies assist in early identification of affected individuals, and in these children neonatal testing and prophylactic thyroidectomy under the age of 6 months is recommended. The presence of transmural ganglioneuromatosis in 90 % of MEN 2B individuals can fortuitously lead to identification of affected children as a result of intestinal biopsy to investigate possible Hirschprung’s. As should have happened in the boy described in this case study, intestinal ganglioneuromatosis should alert pathologists and clinicians to the possibility of underlying genetic conditions, which include MEN2B and neurofibromatosis. In MEN2B the ganglioneuromas are transmural. Early identification of a child with a new MEN2B mutation can allow prophylactic thyroidectomy to be carried out at an age where it is most likely to be effective.

Following prophylactic thyroidectomy all MEN 2 children will need regular long-term follow up with screening not just for development of MTC despite the thyroidectomy, but also for phaeochromocytoma in both MEN 2A and 2B, and parathyroid overactivity in MEN 2A. Most centres will screen for phaeochromocytoma with 6 monthly urinary fractionated metanephrines from 5 years of age, although in reality development of a phaeo in MEN is unlikely before the age of 10 years. Fortunately, parathyroid adenomas do not generally appear until late adolescence at the earliest.