Malignant tumors in children with neurofibromatosis Type 1

Neurofibromatosis type I (NF1) is the monogenic inherited syndrome with established variability of clinical manifestations and the predisposition to the development of malignant tumors. Studying NF1 association with different types of cancers in children is necessary to understand the risk of their occurrence and the prognosis of the disease as well as subsequent studies of this predisposition. Aim. Analysis the clinical data of patients with NF1 and malignant and benign tumors arisen in them. Methods. A retrospective analysis of clinical data of 19 patients from 0 to 18 years old with a malignant tumor, carried out in N.N. Blokhin NMRCO from 1997 to 2018. Results. The clinical signs of NF1 showed an age-dependent timing of their onset. Embryonal tumors were the most common and occurred in 11 out of 19 patients (57.9%), embryonal rhabdomyosarcoma predominated (42.1%), more often affecting the urogenital tract. Familial NF1 was found in 31.6% of patients. NF1 disease of the parents of these children (in four mothers and two fathers) was limited to pigmented skin lesions and multiple neurofibromas. Genetic testing of NF1 gene in three families of children with embryonal tumors revealed 2 de novo mutations — p.V2635FS & p.W1314X and one inherited from father to son (p.2363_2365del). Malignant peripheral nerve sheath tumors developed in 15.8% of patients by puberty. Soft tissue sarcomas and hematopoietic tumors occurred in 10.5% of patients, respectively. Melanoma was found in one patient (5.3%). Conclusion. The data obtained make it possible to supplement the diapason of types of malignant tumors in children associated with NF1 and the possibility of their use in clinical practice for a more rational and targeted observation for patients. Further study of the molecular genetics and clinical aspects of NF1 is necessary for the development of promising therapies for NF1.