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While most individuals with a clinical diagnosis of Neurofibromatosis type 1 (NF1) have a detectable pathogenic variant in the NF1 gene, other conditions have phenotypic features overlapping with NF1. Without molecular confirmation, individuals may be misdiagnosed and have a different underlying condition. Namely, if a child has constitutional mismatch repair deficiency (CMMRD), early detection and prevention strategies for cancer risk would include surveillance recommendations not typically recommended for children with NF1. This study aimed to explore phenotypes of individuals with a clinical diagnosis of NF1 to identify subpopulations who may benefit from further genetic counseling or testing for an alternate diagnosis. Retrospective review of 240 medical records of children who attended a neurocutaneous clinic identified 135 children with a molecularly confirmed pathogenic variant in NF1 or autosomal dominant pattern of clinical NF1 (“controls”) and 102 children deemed “at-risk” for another condition like CMMRD. Clinical presentation, family history of NF1, personal history of cancer, and family history of cancer were compared. When comparing clinical presentation, family history, and cancer history, minimal statistical differences were found, indicating that the at-risk population appears clinically indistinguishable from those with a clear diagnosis of NF1. Given the lack of distinguishable features between the at-risk and control population, this study suggests that tiered genetic testing for all individuals being evaluated for NF1 may be beneficial for identifying patients who may be misdiagnosed with NF1 and subsequently mismanaged. This study suggests that at-risk population with a suspected NF1 diagnosis may benefit from further evaluation. Correct diagnosis of constitutional mismatch repair deficiency is crucial to diagnose cancer at an early stage or prevent cancer from occurring.Prevention relevance:This study suggests that at-risk population with a suspected NF1 diagnosis may benefit from further evaluation. Correct diagnosis of constitutional mismatch repair deficiency is crucial to diagnose cancer at an early stage or prevent cancer from occurring.

Supplementary Data from A Retrospective Chart Review of Children in Neurocutaneous Clinic Who May Benefit from Further Evaluation Beyond Neurofibromatosis Type I