An association of multiple endocrine neoplasia 2B, a RET mutation; constipation; and low substance P–nerve fiber density in colonic circular muscle

Substance P and vasoactive intestinal peptide are reduced in right transverse colon in pediatric slow‐transit constipation

“…The role of neurotransmitters in pediatric STC remains controversial, as changes in neurotransmitters may be primary or secondary. A reduction in SP‐IR with normal NOS‐IR and VIP‐IR has been demonstrated in a constipated child with Multiple Endocrine Neoplasia 2B, despite ganglioneuromatosis 79 . In this child, the selective loss of SP in only the nerve fibers was thought to be primary, with constipation a secondary phenomenon.…”

Medullary thyroid carcinoma in a 2-month-old male with multiple endocrine neoplasia 2B and symptoms of pseudo-Hirschsprung disease: a case report

“…A reasonable number of case reports and series of patients with MEN 2B have been published [10][11][12][13][14][15][16][17]. To our knowledge, the youngest patient was a few weeks old when MEN 2B was suspected, and a total thyroidectomy was performed at the age of 9 months [18].…”

Multiple endocrine neoplasia 2B: Differential increase in enteric nerve subgroups in muscle and mucosa

“…This is thought to be because the lack of nerve cells provides no sites for the extrinsic nerves to synapse onto. In MEN2B submucosa, the nerve fibres also form large cables but with nerve cells present in many ectopic ganglia[ 18 , 20 ]. The presence of neurons among the enlarged nerve fibres has been reported previously as the diagnostic criterion to distinguish MEN2B from Hirschsprung's disease[ 18 ].…”

“…Thus, RET overactivation increased all nerve fibres in the myenteric ganglia, NOS in the circular muscle, and VIP and SP in the submucosal ganglia and mucosa. Previous studies have shown histology of ganglia and staining with neuron specific enolase (NSE)[ 12 , 15 , 19 ] but only one other study has reported labelling for specific neurotransmitters[ 20 ]. Previously, in seromuscular biopsies from 2 other MEN2B patients, we noted a decrease in SP in the circular muscle.…”

“…Constipation is present in many MEN2B patients[ 1 , 2 , 7 , 12 , 14 - 16 ], and they may present in the neonatal period with symptoms suspiciously like Hirschsprung disease (HSCR)[ 2 , 16 - 20 ]. Indeed, MEN2B can be diagnosed in the neonatal period, by the presence of neurons among the enlarged nerves in submucosal ganglia in standard rectal biopsies[ 16 , 18 , 21 ].…”