Neurofibromatosis type 1 (NF1) is a severe monogenic disorder characterized by café-au-lait spots and neoplastic lesions, including plexiform neurofibromas that are treated with targeted therapy using a mitogen-activated protein kinase inhibitor. A sporadic case of NF1 caused by a unique, previously unreported NF1 gene mutation, c.1369_1370insGGGTC(p.H457fs), was identified in a 13-year-old boy. The features of NF1 in the patient included early manifestation of tumor syndrome with simultaneous development of cutaneous neurofibromas, tumors of spinal roots, vagus nerve and plexiform neurofibromas, cognitive and speech impairment, growth retardation, and multiple skeletal abnormalities. At the age of 10, targeted therapy was initiated, resulting in a significant tumor size reduction and thus indicating the effectiveness of this approach in NF1 caused by this pathogenic NF1 variant.
R. Mustafin· Pediatric Hematology/Oncolog...· 0 citations
Background.
Neurofibromatosis type 1 (NF1) is an autosomal dominant tumor syndrome characterized by marked polymorphism of clinical manifestations. There is evidence of genotypic correlations in NF1 with more pronounced manifestations of the disease with certain mutations in the
NF1
gene. therefore, it is important to describe patients with a specific mutation and a severe NF1 phenotype.
Purpose of the study
: to describe the genetic and clinical features of NF1 and its treatment tactics in the patient with severe manifestations of the disease and a unique mutation in the
NF1
gene.
Material and Methods.
A ten-year-old girl with a sporadic case of NF1 was examined, X-ray examination was performed, a blood sample was taken with DNA extraction and sanger sequencing of the
NF1
gene.
Results.
The patient was identified to have a unique pathogenic variant c.240_241del(p.Y80fs) in the NF1 gene, and the following clinical manifestations of NF1: retrocerebellar brain cyst, femur plexiform neurofibroma, grade 3 scoliosis, and femur fibrous dysplasia. successful surgical correction of the scoliosis was performed. targeted therapy with selumetinib was prescribed for femur plexiform neurofibroma treatment.
Conclusion.
the identified NF1 variant: c.240_241del(p.Y80fs) has not previously been described in the scientific literature and is not included in the ClinVar database. the clinical manifestations of NF1, characterized by severe combined lesions, have been described. treatment of such cases of NF1 requires a combination of targeted therapy and high-tech surgery.
R. Mustafin· Siberian journal of oncology· 0 citations