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Multiple endocrine neoplasia type 4: a new member of the MEN family
Hélène Singeisen1, Mariko Melanie Renzulli2, Vojtech Pavlicek1
1Department of Internal Medicine, Endocrinology, Cantonal Hospital Thurgau, Münsterlingen, Switzerland.
Objective:
Multiple endocrine neoplasia type 4 (MEN4) is caused by a CDKN1B germline mutation first described in 2006. Its estimated prevalence is less than one per million. The aim of this study was to define the disease characteristics.
Methods:
A systematic review was performed according to the PRISMA 2020 criteria. A literature search from January 2006 to August 2022 was done using MEDLINE® and Web of ScienceTM.
Results:
Forty-eight symptomatic patients fulfilled the pre-defined eligibility criteria. Twenty-eight different CDKN1B variants, mostly missense (21/48, 44%) and frameshift mutations (17/48, 35%), were reported. The majority of patients were women (36/48, 75%). Men became symptomatic at a median age of 32.5 years (range 10-68, mean 33.7 ± 23), whereas the same event was recorded for women at a median age of 49.5 years (range 5-76, mean 44.8 ± 19.9) (P = 0.25). The most frequently affected endocrine organ was the parathyroid gland (36/48, 75%; uniglandular disease 31/36, 86%), followed by the pituitary gland (21/48, 44%; hormone-secreting 16/21, 76%), the endocrine pancreas (7/48, 15%), and the thyroid gland (4/48, 8%). Tumors of the adrenal glands and thymus were found in three and two patients, respectively. The presenting first endocrine pathology concerned the parathyroid (27/48, 56%) and the pituitary gland (11/48, 23%). There were one (27/48, 56%), two (13/48, 27%), three (3/48, 6%), or four (5/48, 10%) syn- or metachronously affected endocrine organs in a single patient, respectively.
Conclusion:
MEN4 is an extremely rare disease, which most frequently affects women around 50 years of age. Primary hyperparathyroidism as a uniglandular disease is the leading pathology.
Insights
Multiple endocrine neoplasia type 4 (MEN4), a rare genetic disorder caused by CDKN1B mutations, predominantly affects women. Primary hyperparathyroidism is the most common initial endocrine manifestation.
Area of Science:
- Endocrinology
- Genetics
- Oncology
Background:
- Multiple endocrine neoplasia type 4 (MEN4) is an extremely rare disorder, with an estimated prevalence of less than one per million.
- MEN4 is caused by germline mutations in the CDKN1B gene, a condition first identified in 2006.
Purpose of the Study:
- To define the clinical and pathological characteristics of Multiple Endocrine Neoplasia type 4 (MEN4).
- To analyze the spectrum of CDKN1B variants and their association with disease presentation.
Main Methods:
- A systematic literature review was conducted following PRISMA 2020 guidelines.
- Searches were performed in MEDLINE and Web of Science databases from January 2006 to August 2022.
- Data from 48 symptomatic patients meeting eligibility criteria were analyzed.
Main Results:
- Twenty-eight distinct CDKN1B variants were identified, predominantly missense and frameshift mutations.
- The majority of affected patients were women (75%), with a median age of symptom onset at 49.5 years.
- The parathyroid gland was the most frequently affected endocrine organ (75%), often presenting as uniglandular disease, followed by the pituitary gland (44%).
Conclusions:
- Multiple Endocrine Neoplasia type 4 (MEN4) is a rare condition predominantly affecting women around age 50.
- Primary hyperparathyroidism, particularly as a uniglandular disease, is the leading initial endocrine pathology in MEN4 patients.
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