Multiple Endocrine Neoplasia, Type IIB

Clinical Characteristics
Ocular Features: 

Corneal nerves are medullated and appear prominent.  Neuromas of the lid margins and sometimes the conjunctiva are common features.  Thickening of the entire eyelids may be present.

Systemic Features: 

Some manifestations may be seen in early childhood.  Prominent physical features include full lips, thickened eyelids, high arched palate and a marfanoid habitus.  Medullary carcinoma of the thyroid is almost always present and can be the cause of death in relatively young individuals. Metastases are usually to the regional lymph nodes or to liver, lungs, or bone. Pheochromocytomas and megacolon secondary to gastrointestinal neuromas are commonly seen.  The esophagus sometimes lacks normal motility for the same reason.  Neuromas often lead to thickening of the lips and tongue and can also appear as pedunculated nodules on these structures.  Cafe-au-lait spots and increased pigmentation of the hands, feet, and circumoral areas are frequently present.  Many patients have dysmorphic features suggestive of Marfan syndrome including a typical habitus, pectus excavatum, scoliosis, and pes cavus. Proximal myopathy and peripheral neuropathy are sometimes seen.

Another form of multiple endocrine neoplasia, called MEN2A, differs in the absence of mucosal neuromas and the marfanoid habitus.  MEN2A patients are more likely to have parathyroid hyperplasia.


This is an autosomal dominant disorder caused by mutations in the tyrosine kinase domain of the RET gene (10q11.2). This disorder (MEN2B) may be allelic to MEN2A.  Perhaps half of MEN2B cases occur sporadically and in these the mutant RET allele is usually of paternal origin.

Treatment Options: 

Treatment of local lesions is sometimes indicated.  Biochemical testing for pheochromocytoma should be done before any surgery.

Article Title: 


Morrison PJ, Nevin NC. Multiple endocrine neoplasia type 2B (mucosal neuroma syndrome, Wagenmann-Froboese syndrome). J Med Genet. 1996 Sep;33(9):779-82. Review.

PubMedID: 8880581

Carlson KM, Bracamontes J, Jackson CE, Clark R, Lacroix A, Wells SA Jr, Goodfellow PJ. Parent-of-origin effects in multiple endocrine neoplasia type 2B. Am J Hum Genet. 1994 Dec;55(6):1076-82.

PubMedID: 7977365