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The great mimicker: Phenotypic overlap between constitutional mismatch repair deficiency and Tuberous Sclerosis complex
Author(s) -
Shapira Rootman Mika,
Goldberg Yael,
Cohen Rony,
Kropach Nesia,
Keidar Inbal,
Friedland Rivka,
Dotan Gad,
Konen Osnat,
Toledano Helen
Publication year - 2020
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1111/cge.13656
Subject(s) - neurofibromatosis , tuberous sclerosis , medicine , dermatology , pathology , dna mismatch repair , cancer , colorectal cancer
Constitutional mismatch repair deficiency is a rare cancer predisposition syndrome caused by biallelic mutations in one of the four mismatch repair genes. Patients are predisposed to various tumors including hematological malignancies, brain tumors and colorectal carcinomas. Phenotypic overlap with Neurofibromatosis‐1 is well known, with most patients presenting with café‐au‐lait macules. Other common features include axillary and/or inguinal freckling and intracranial MRI foci of high T2W/FLAIR signal intensity similar to the typical FASI seen in Neurofibromatosis‐1. In this cohort of eight patients with constitutional mismatch repair deficiency we describe overlapping phenotypical features with Tuberous Sclerosis complex. In addition to “ash‐leaf like” hypomelanotic macules (five patients), we detected intracranial tuber‐like lesions (three patients), renal cysts (three patients) and renal angiomyolipomas (two patients). All our patients also had Neurofibromatosis‐1 like features, mainly café‐au‐lait macules. This study suggests that features of Tuberous sclerosis especially when overlapping with those of Neurofibromatosis 1 or malignancies atypical for these syndromes should raise the possibility of constitutional mismatch repair deficiency. Correct diagnosis is essential for appropriate genetic counseling and pre‐emptive cancer surveillance.