Multiple idiopathic mucosal neuromas: A minor form of multiple endocrine neoplasia type 2B or a new entity?,☆☆

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Abstract

Multiple endocrine neoplasia type 2B (MEN 2B) is a rare autosomal dominant process characterized by medullary thyroid carcinoma, pheochromocytoma, and mucosal neuromas. A point mutation at codon 918 of the RET protooncogene has been observed in approximately 90% of patients and families with MEN 2B. Mucosal neuromas are the most consistent and distinctive feature (100% of patients) of MEN 2B and are considered pathognomonic. We describe a 35-year-old woman with mucosal neuromas of the lower lip and tongue that appeared in early childhood. Examination did not reveal other abnormalities. After a follow-up of more than 22 years with periodic clinical, biochemical, and radiologic studies, no evidence of MEN 2B has been detected. Analysis of the RET protooncogene exons 10, 11, and 16 did not demonstrate point mutation in the MEN 2B region (M918T). (J Am Acad Dermatol 1997;37:349-52.)

Section snippets

CASE REPORT

A 35-year-old woman had multiple painless papules on the lower lip and tongue that had appeared at age 7. Past medical and familial history were unremarkable.

At age 12 examination revealed an apparently healthy girl whose height and weight were within the normal range. Multiple nontender pedunculated papules and nodules, 2 to 25 mm in diameter, were seen on the lateral and dorsal aspects of the tongue (Fig. 1) .

. Clinical features in 1974: Multiple papules on lateral and dorsal aspects of

RET protooncogene mutation analysis

RET protooncogene mutations were evaluated by polymerase chain reaction (PCR) and by either a single-strand conformational polymorphism (SSCP) analysis (exons 10, 11, and 16), restriction analysis (exon 16), and direct sequencing. Briefly, genomic DNA was obtained from peripheral blood and purified. 7 Amplification of exons 10, 11, and 16 was performed by means of specific primers 8 (10SE: CTCAGGGGGCAGCATTGTT and 10 AN: CACTCACCCTGGATGTCTT; 11SE: CCTCTGCGGTGCCAAGCCTC and 11AN:

RESULTS

PCR-SSCP analysis of exons 10, 11, and 16 did not show bands with altered migration relative to wild control samples. FokI enzyme restriction analysis demonstrated the presence of the restriction site in both alleles of exon 16 (Fig. 3) .

. Restriction analysis of PCR-products of RET exon 16 with FokI. The ATG to ACG point mutation at codon 918 removes a FokI restriction site in positive control (lane 3). Both negative control (lane 1) and present patient (lane 2) show complete digestion,

DISCUSSION

MEN 2B is a rare syndrome that can occur sporadically or can be inherited in an autosomal dominant pattern. It is characterized by the concurrence of mucosal neuromas, MTC, and pheochromocytoma. 3

Other commonly associated manifestations are thickened corneal nerves and ganglioneuromatosis of the alimentary tract. Physical features of patients with MEN 2B (the mucosal neuroma syndrome) include marfanoid appearance with arachnodactyly, poor muscular development, and little subcutaneous fat.

References (22)

  • O Hiort et al.

    Detection of point mutations in the androgen receptor gene using nonisotopic single strand conformation polymorphism analysis

    Hum Mol Genet

    (1994)
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    Reprint requests: Ramon M. Pujol, MD, Department of Dermatology, Hospital de la Santa Creu i Sant Pau, Avda. Sant Antoni M. Claret 167, 08025, Barcelona, Spain.

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