Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominantly inherited syndrome. It is caused by loss-of-function mutation of the MEN1 gene, and characterized by variable association of primary hyperparathyroidism, pituitary adenomas and neuroendocrine tumours (NETs). Up to 3% of MEN1-like syndromes present a loss-of-function mutation in the tumour-suppressor gene CDKN1B, and therefore constitute MEN4 syndrome. Data on MEN4 clinical behaviour, penetrance and associated manifestations are still incomplete.
We report the case of a young woman diagnosed with a rare NET G1 of the appendix at the age of 18 years. Genetic analysis revealed a germline missense mutation (c.397C>A), present in heterozygosity, of codon 133 in the CDKN1B gene. To date only 26 mutations of CDKN1B have been described in association with a MEN4 phenotype. Subsequently, the patient’s sister, father and paternal uncle were found to be carriers of the same mutation but showed no clinical or biochemical signs of disease.
This is currently the youngest case of MEN4 with a gastrointestinal tract NET reported in the literature, and the first with appendiceal involvement. Despite the absence of disease within the proband’s family, ongoing screening would seem to be warranted, along the lines of that described by other authors for MEN1 patients.
KEY WORDS: MEN4, CDKN1B mutations, youngest case of NET in MEN4, appendiceal NET, MEN4 review.
