Neurofibromatosis type 1 (NF1) is an autosomal dominant cancer predisposition syndrome caused by pathogenic variants in NF1, which negatively regulates the RAS pathway. Knowledge of the genotype-phenotype correlation in this disease is an important tool for prognostic evaluation and early detection of malignant peripheral nerve sheath tumors (MPNST), present in approximately 10% of these patients. We present the case of a teenager with a left jaw MPNST and a previously unreported germline pathogenic variant on NF1.
An 11-year-old female with a NF1 clinical diagnosis was referred to our hospital with a MPNST in an advanced state. A previously unreported NF1 pathogenic variant was obtained (GRCh37: NM_182493.2 c.3299C>G, p.Ser1100*). Despite great efforts from the surgical and medical teams, the tumor progression couldn't be halted, resulting in the patient's death.
As MPNSTs are refractory to current treatment regimens, early diagnosis, and development of new therapies, such as MEK inhibitors, is necessary for reducing morbidity and mortality within NF1 patients. This increases the importance of a more widespread genetic testing strategy.
The report of a novel NF1 pathogenic variant in a patient with maternally inherited neurofibromatosis type 1 and a MPNST increases the knowledge of the genotype-phenotype correlation in the disease.
Abbreviations:NF1 (Neurofibromatosis Type 1), MPNST (Malignant Peripheral Nerve Sheath Tumors), NIH (National Institutes of Health), SARS-CoV2 (Severe Acute Respiratory Syndrome due to Coronavirus Type 2), CT (Computed Tomography), MEK (MAP kinase)
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Published online: April 15, 2023
Accepted: April 14, 2023
Received in revised form: April 3, 2023
Received: December 5, 2022
Sources of Support: Invitae Corporation 1400 16th Street, San Francisco, CA 94,103 (acknowledgment for sponsored molecular testing)
No other funding sources to declare.
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