Background and purpose :
Constitutional mismatch repair deficiency :(CMMRD) 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 CMMRD we describe overlapping phenotypical features with Tuberous Sclerosis complex.
Materials and Methods:
Medical and imaging records of eight subjects with genetically confirmed CMMRD being followed at our tertiary children’s medical center were reviewed. Medical files were evaluated for age at presentation, malignant and non-malignant lesions in the various organ systems especially brain, skin, eyes and kidneys. All available imaging studies were reviewed by a certified pediatric radiologist and evaluated for: (1) intracranial imaging features overlapping those of TSC. (2) renal lesions including angiomyolipomas and cysts. (3) Intra and extracranial NF-1-like features (4) additional imaging features described in CMMRD such as intracranial developmental venous anomaly (DVA).
Results:
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). In addition, two patients were found to have congenital hypertrophy of retinal pigment epithelium also described in Tuberous sclerosis. All our patients also had Neurofibromatosis-1 like features, mainly café-au-lait macules.
Conclusion:
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 CMMRD. Correct diagnosis is essential for appropriate genetic counselling and pre-emptive cancer surveillance.
