Background. Phacomatosis pigmentokeratotica (PPK) is an orphan genodermatosis from the epidermal nevus syndrome group. This disease is caused by somatic mosaicism predominantly in the HRAS gene. Pathognomonic PPK sign is combination of congenital linear nevus sebaceus of Jadassohn and speckled lentiginous nevus. Second one may debut much later. In some cases, there are signs of nervous system damages, skeletal disorders, visual impairments. Case description. Description of a patient with PPK and novel for this disease mosaic variant G469A in the BRAF gene is presented. Clinical picture included typical signs of the syndrome and immunological disorders unusual for patients with PPK. Possible genotype-phenotype correlations were analyzed based on 16 previously published observations of genetically verified PPK. Conclusion. The syndrome rarity, its course variability, and patients genetic testing features determine the difficulties in PPK diagnosis. The disease should be considered not only in terms of dermatological signs, but also regarding comorbid disorders. The dynamic follow-up should include consultations of pediatric oncologist, neurologist, ophthalmologist, endocrinologist, orthopedist, cardiologist, and immunologist.

Background Familial adenomatous polyposis (FAP) is a rare genetic disorder that is inherited in an autosomal dominant fashion. This disease is caused by a germline mutation in the APC gene, but in 20-30% of cases the disease occurs due to de novo mutations. There are several forms of the disease from severe, which is characterized by a pronounced number of polyps throughout the gastrointestinal tract (GIT) to a mild (attenuated) form of FAP, with less than 100 colonic polyps. According to various scientific literature, the risk of malignancy of epithelial formations reaches 100%. Identified epithelial formations of the gastrointestinal tract will lie down for endoscopic or surgical treatment. FAP is also characterized by neoplasms of extraintestinal localization, which characterizes it as a multisystem syndrome. There is a high risk of developing congenital retinal pigment epithelium hypertrophy, bone osteoma, fibroma, angiofibroma of the nose, thyroid carcinoma, hepatoblastoma, brain tumor and pancreatic tumor. Congenital retinal hypertrophy is the earliest extraintestinal manifestation of FAP. Thyroid cancer in young people, as a rule, is diagnosed first and serves as the basis for a comprehensive endoscopic diagnosis of the gastrointestinal tract. We present a rare case of FAP in a 14-year-old child associated with malignant neoplasms of extraintestinal localizations.

Background. Proteus syndrome is extremely rare congenital multisystem disease with high variability in clinical manifestations. Its prevalence is unknown, there are less than 200 cases in the world literature. The syndrome is a classic example of somatic mosaicism, and all target drugs for its management are based on it. Clinical case description. This article describes two clinical cases with somatic variants of the nucleotide sequence in the AKT1 gene, mosaic form, revealed by the NGS method. Target drug (mTOR-inhibitors group) was assigned in one case. Conclusion. The description of the phenotypic features of patients with Proteus syndrome is crucial as this pathology is very rare. It is necessary to increase the awareness of clinicians about this disease to develop a plan for dynamic follow-up with consideration to life-threatening complications (malignant tumors and thrombembolia risk). Genetic verification of Proteus syndrome is mandatory nowadays as target therapy is actively developed and implemented, thus, revision of clinical guidelines is recommended.

Background . Hereditary polyposis syndromes (HPS) are a group of rare genetic diseases characterized by multiple epithelial lesions in the gastrointestinal tract (GIT) with high risk of malignancy and neoplasia development in other localizations. The case follow-up tactics in hereditary polyposes have significant differences, and differential diagnosis can be complicated due to the phenotype variability and the clinical manifestations similarity. Objective. The aim of the study is to determine the role of molecular genetic testing and endoscopic examination in the diagnosis and management of children with HPS. Materials and methods . The retrospective observational study included 17 patients with clinical signs of hereditary polyposes who applied to the L.A. Durnov Research Institute of Pediatric Oncology and Hematology during the period from 2013 to 2023. All patients underwent molecular genetic testing and comprehensive endoscopic examination of upper and lower GIT. Results . We have divided patients into 7 groups according to the results of genetic testing. Patients had various mutations in genes associated with hereditary tumor syndromes: STK11 (35.3%; n = 6), APC (17.6%; n = 3), PTEN (11.8%; n = 2), SMAD4 (5.9%; n = 1), BMPR1A (5.9%; n = 1), MUTYH (5.9%; n = 1), MLH1 (5.9%; n = 1). One female patient with colorectal cancer with history of adenomatous polyp had pathogenic variants in the ATM and CHEK2 genes; it could be considered as multi-locus tumor syndrome (MINAS) (5.9%, n = 1). Another female patient (5.9%) had multiple gastric body hamartoma polyps and multiple gastric gastrointestinal stromal tumors (GIST) but with no pathogenic mutations. Complex endoscopic examination was performed in 14 (82.3%) patients. Epithelial or non-epithelial lesions of the stomach and intestine were revealed in all cases. Malignant tumors of duodenum and colon were diagnosed in 3 out of 14 patients (21.4%). Morphological variants of these GIT lesions were represented by hamartoma, hyperplastic, and juvenile polyps, adenomas, serrated adenomas, adenocarcinoma, and GIST. The diagnosed epithelial lesions of the stomach, duodenum, and colon were removed via endoscopic polypectomy and endoscopic mucosal resection in 8 out of 14 patients (57.1%). Some cases required small bowel resection (14.3%, n = 2), total colectomy (14.3%, n = 2), and gastrectomy (14.3%, n = 2). Conclusion . Understanding the molecular and biological etiology of HPS, its endoscopic diagnosis, and treatment features allows us to optimize the management of such patients and to minimize the risks of developing malignant tumors in upper and lower GIT, as well as extraintestinal tumors by carrying out timely medical and preventive measures.

malignant neoplasms (MNP). The frequency of PNS in MNP ranges from 1 to 20 % according to different authors. One of the manifestations of PNS is acne, which occurs against the background of malignant neoplasm due to hormonal disorders. The presented article describes a clinical case of a patient with a mixed germ cell tumor and metastases in the retroperitoneal lymph nodes. The germ cell tumor produced human beta-chorionic gonadotropin, which led to the development of acne as a PNS. Antitumor treatment (surgical removal of the tumor and polychemotherapy) normalized the levels of human beta-chorionic gonadotropin and serum testosterone, which in turn led to regression of acne without acne therapy.

Gorlin-Golts syndrome is a genetic determined disease, characterized by multisystem features and associated with different malignancies, which are more aggressive with very unfavorable prognosis. By literature data this syndrome is a rare pathology. Observation and treatment of patients with Gorlin-Golts syndrome include syndromic correction of clinical presentations and detailed observation for early malignancies detection. In the current issue a survey of modern literature about Gorlin-Golts syndrome in children and clinical case of patient sent to Federal State Budgetary Institution» N. N. Blokhin National Medical Research Center of Oncology «of the Ministry of Health for malignancy diagnosis are presented. By global and own clinical experience about Gorlin-Golts syndrome it is necessary a genetic verification and make us perform a multidisciplinary control for such patient health with obligatory examination and observation of pediatric oncologist.

Genodermatoses are a heterogeneous group of hereditary diseases that are characterized by predominantly skin lesions. To date, there are more than 200 genetically determined skin diseases, representing about 35 % of all hereditary syndromes. In some cases, skin lesions may be the only manifestation of the disease, but still more often, they occur in combination with disorders of other organ systems. In many cases, genodermatoses are associated with an increased risk of malignancy which makes early detection of hereditary syndromic pathology especially important for cancer prevention.This review provides a brief description of the dermatological manifestations as well as other phenotypic features of a number of genodermatoses, their genetic nature, and the strategy of management.

Background. According to the data of the world literature and own data of observations renal cell carcinoma (RCC) in children is a rare pathology. There are mainly localized and locally common forms of the disease, characterized by a good prognosis and rare reccurence. The tactic of the treatment in this group of patients based on radical surgery. If there are distant metastases, adjuvant chemotherapy is performed. The drug of choice in metastatic forms is a tyrosine kinase ingibitor. Description of a Clinical Case. A review of the world literature on the problem of RCC in children and also the clinical observation of RCC in a 6 years old patient, who treated in N.N. Blokhin National Medical Research Center of Oncology (Moscow), are presented. Now the patient is healthy and is under the dynamic observation. Conclusion. The rarity of RCС requires careful examination and observation of patients, morphological and molecular-genetic study of the tumor for features of biology and develop of «adult» cancer in children.