The great mimicker: Phenotypic overlap between constitutional mismatch repair deficiency and Tuberous Sclerosis complex
| Autor: | Nesia Kropach, Osnat Konen, Rivka Friedland, Rony Cohen, Gad Dotan, Mika Shapira Rootman, Yael Goldberg, Helen Toledano, Inbal Keidar |
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| Rok vydání: | 2019 |
| Předmět: |
Male
0301 basic medicine Inguinal freckling Pathology medicine.medical_specialty Neurofibromatosis 1 Adolescent Genetic counseling 030105 genetics & heredity Fluid-attenuated inversion recovery DNA Mismatch Repair 03 medical and health sciences Tuberous sclerosis Neoplastic Syndromes Hereditary Tuberous Sclerosis Neoplasms Genetics medicine Humans Genetic Predisposition to Disease Neurofibromatosis Child Genetics (clinical) Brain Neoplasms business.industry Cafe-au-Lait Spots Cancer medicine.disease Hypomelanotic macule Magnetic Resonance Imaging Pedigree 030104 developmental biology Child Preschool Mutation Female DNA mismatch repair Colorectal Neoplasms business |
| Zdroj: | Clinical Genetics. 97:296-304 |
| ISSN: | 1399-0004 0009-9163 |
| DOI: | 10.1111/cge.13656 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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