Table 1.
Studies describing families with MEN4 syndrome associated with CDKN1B mutations.
| Mutation | Type of mutation | Carriers with MEN4-associated features | Asymptomatic family carriers (age at assessment) | Total carriers | Reference | ||
|---|---|---|---|---|---|---|---|
| Sex | Main MEN features (age at diagnosis) | Other significant history of neoplasia | |||||
| c.G692A (p.W76X) | Nonsense | F | GH-producing pituitary macroadenoma (30 years old) Primary hyperparathyroidism (PHPT) (46 years old) |
NO | One sister without MEN main features but with a history of angiomyolipoma diagnosed at 52 years old. Another sister (44 years old) and her daughter (16 years old) completely asymptomatic. | 4 | Pellegata et al. (2) |
| c.59_77dup19 (pK25fs) | Frameshift | F | Small-cell neuroendocrine cervical carcinoma (45 years old) ACTH-secreting pituitary adenoma (46 years old) PHPT (47 years old) |
NO | None | 1 | Georgitisi et al. (10) |
| ATG-7G>C | Mutation in 5′UTR | F | PHPT (61 years old) | Bilateral NF adrenal masses (63 years old) | 2 daughters (46 and 48 years old) | 3 | Agarwal et al. (11) |
| c283C>T (p.P95S) | Missense | F | PHPT with multiple adenoma (46 years old), metastatic gastrinoma (50 years old) | NO | None | 1 | Agarwal et al. (11) |
| c.595T>C (p.*199Qext60) | Nonsense | F | PHPT with multiple adenoma (50 years old) | NO | None | 2 | Agarwal et al. (11) |
| F | PHPT (66 years old) | NO | Agarwal et al. (11) | ||||
| c.163G>A (p.Ala55Thr) | Missense | F | Metastatic gastrinoma (42 years old) PHPT (51 years old) |
NO | None | 1 | Belar et al. (12) |
| c.678C>T (p.P69L) | Missense | F | PHPT (67 years old) Metastatic bronchial carcinoid (67 years old) Non-functioning pituitary microadenoma (79 years old) |
Papillary thyroid carcinoma (64 years old) | None | 1 | Molatore et al. (13) |
| c.-456_-453delCCTT | Deletion in 5′UTR | F | GH-secreting adenoma (62 years old) Non-functioning pancreatic NET (62 years old) |
NO | None | 1 | Occhi et al. (14) |
| c.374_375delCT | Frameshift | F | PHPT from multiple adenoma (41 years old) Metastatic gastrinoma (50 years old) |
NO | 1 son (34 years old) | 2 | Tonelli et al. (15) |
| c.25G>A (Gly9Arg) | Missense | M | PHPT (68 years old) | NO | None | 1 | Costa-Guda et al. (16) |
| c.397CA (p.Pro133Thr) | Missense | F | PHPT (53 years old) | NO | None | 3 | Costa-Guda et al. (16) |
| F | PHPT (56 years old) | Papillary thyroid carcinoma (56 years old) Uterine leiomyoma (NA) Grade II meningioma (NA) |
None | Bugalho and Domingues (17) | |||
| F | PHPT from multiple adenoma(49 years old) Mutation also in MEN1 |
Fibrocystic breast disease (NA) | None | Borsari et al. (8) | |||
| c.-80C>T | Missense | M | PHPT (38 years old) | NO | None | 1 | Borsari et al. (8) |
| c.-29_-26delAGAG | Deletion in 5′UTR | F | PHPT (61 years old) | NO | None | 5 | Borsari et al. (8) |
| F | GH-secreting pituitary adenoma (5 years old) | NO | Mother (age not reported) | Sambugaro et al. (18) | |||
| F | Gastric carcinoid tumor (69 years old) PHPT (74 years old) |
NO | None | Malanga et al. (19) | |||
| M | ACTH-secreting pituitary microadenoma (13 years old) | NO | None | Chasseloup et al. (20) | |||
| c378G>C (pE126D) | Missense | F | PHPT (15 years old) | NO | Mother (46 years old) Grandfather (74 years old) |
3 | Elston et al. (21) |
| c.320delA (p.Q107Rfs*12) | Frameshift | F | ACTH-secreting pituitary microadenoma (16 years old) | NO | 4 (mother, brother, and 2 children) | 5 | Chasseloup et al. (20) |
| c.376G>C (p.E126Q) | Missense | F | ACTH-secreting pituitary microadenoma (12 years old) | NO | None | 1 | Chasseloup et al. (20) |
| c.407A>G (p.D136G) | Missense | M | ACTH-secreting pituitary microadenoma (15 years old) | NO | None | 1 | Chasseloup et al. (20) |
| c.356T>C (p.I119T) | Missense | F | ACTH-secreting pituitary microadenoma (15 years old) | NO | None | 2 | Chasseloup et al. (20) |
| F | GH-secreting adenoma (NA) | NO | (aunt with GH-secreting adenoma, not tested for CDKN1B mutation) | Tichomirowa et al. (22) | |||
| c.286AOC (p.K96Q) |
Missense | F | PRL-secreting adenoma (NA) | Breast cancer (41 years old) | 1 sister (age not reported) | 2 | Tichomirowa et al. (22) |
| c.285dupC (Lys96Glnfs*29) | Duplication | M | PHPT (60 years old) | Positive for NF1. Prostate cancer with transdifferentiation in metastatic small cell carcinoma (60 years old) Multiple spinal neurofibromas |
None | 1 | Brock et al. (23) |
| c.281C>T, (Pro94Leu) | Missense | F | Hyperprolactinemia (adenoma non-detected at MRI) (35 years old) PHPT (51 years old) |
Breast cancer (37 years old) Ovarian serous cystadenoma (50 years old) Multifocal papillary thyroid carcinoma (55 years old) |
None | 1 | Chevalier et al. (24) |
| c.206C>T, p. (Pro69Leu9) | Missense | F | Non-functioning macroadenoma (66 years old) PHPT (66 years old) |
Subclinical cortisol autonomous secretion by adrenal adenoma (NA) | None | 1 | Chevalier et al. (24) |
| c.121_122 delTT (pLeu41Asnfs*83 | Frameshift | F | PHPT and ACTH-secreting pituitary microadenoma (37 years old) | NO | All the patients belong to the same family, no other healthy carrier reported | 13 | Frederkisen et al. (25) |
| F | PHPT and non-functioning pancreatic NET (67 years old) | NO | |||||
| F | PHPT and non-functioning pituitary microadenoma (66 years old) | NO | |||||
| M | PHPT and non-functioning pituitary microadenoma (64 years old) | NO | |||||
| M | PHPT and non-functioning pituitary macroadenoma (46 years old) | NO | |||||
| F | PHPT- and ACTH-secreting pituitary microadenoma (NA) | NO | |||||
| 5F + 2M | PHPT (NA) | One F developed had a recurrency of PHPT after first surgery and had breast cancer (77 years old) | |||||
M, male; F, female; PHPT, primary hyperparathyroidism; NA, not assessed.