Pure mucosal neuroma syndrome, not MEN2B

Area of Science:

• Genetics
• Ophthalmology
• Endocrinology

Background:

• Multiple Endocrine Neoplasia type 2B (MEN2B) presents with marfanoid habitus, thickened corneal nerves, and mucosal neuromas.
• Rarely, individuals exhibit MEN2B features without RET gene mutations or associated endocrine tumors.
• Distinguishing pure mucosal neuroma syndrome (MNS) from MEN2B is crucial for appropriate patient management.

Purpose of the Study:

• To report a case of a patient with MEN2B-like phenotype but without the RET mutation.
• To identify the underlying genetic cause through exome sequencing.
• To highlight the importance of genetic testing in differentiating MNS from MEN2B.

Main Methods:

• Ophthalmological examination to assess conjunctival lesions and corneal nerves.
• Clinical evaluation for characteristic MEN2B phenotypic features.
• Genetic testing including RET proto-oncogene analysis and whole exome sequencing.

Main Results:

• The patient presented with prominent corneal nerves, conjunctival neuromas, marfanoid habitus, and tongue neuromas.
• RET proto-oncogene testing was negative for pathogenic variants.
• Exome sequencing revealed a heterozygous pathogenic son of sevenless-1 frameshift mutation, indicative of MNS.

Conclusions:

• The identified son of sevenless-1 mutation suggests a diagnosis of pure MNS, distinct from MEN2B.
• Pure MNS lacks association with endocrine conditions, differentiating it from MEN2B.
• Accurate diagnosis of MNS can prevent unnecessary prophylactic treatments like thyroidectomy.