Rare clinical phenotype of filaminopathy presenting as restrictive cardiomyopathy and myopathy in childhood.

BACKGROUND: FLNC is one of the few genes associated with all types of cardiomyopathies, but it also underlies neuromuscular phenotype. The combination of concomitant neuromuscular and cardiac involvement is not often observed in filaminopathies and the impact of this on the disease prognosis has hitherto not been analyzed. RESULTS: Here we provide a detailed clinical, genetic, and structural prediction analysis of distinct FLNC-associated phenotypes based on twelve pediatric cases. They include early-onset restrictive cardiomyopathy (RCM) in association with congenital myopathy. In all patients the initial diagnosis was established during the first year of life and in five out of twelve (41.7%) patients the first symptoms were observed at birth. RCM was present in all patients, often in combination with septal defects. No ventricular arrhythmias were noted in any of the patients presented here. Myopathy was confirmed by neurological examination, electromyography, and morphological studies. Arthrogryposes was diagnosed in six patients and remained clinically meaningful with increasing age in three of them. One patient underwent successful heart transplantation at the age of 18 years and two patients are currently included in the waiting list for heart transplantation. Two died due to congestive heart failure. One patient had ICD instally as primary prevention of SCD. In ten out of twelve patients the disease was associated with missense variants and only in two cases loss of function variants were detected. In half of the described cases, an amino acid substitution A1186V, altering the structure of IgFLNc10, was found. CONCLUSIONS: The present description of twelve cases of early-onset restrictive cardiomyopathy with congenital myopathy and FLNC mutation, underlines a distinct unique phenotype that can be suggested as a separate clinical form of filaminopathies. Amino acid substitution A1186V, which was observed in half of the cases, defines a mutational hotspot for the reported combination of myopathy and cardiomyopathy. Several independent molecular mechanisms of FLNC mutations linked to filamin structure and function can explain the broad spectrum of FLNC-associated phenotypes. Early disease presentation and unfavorable prognosis of heart failure demanding heart transplantation make awareness of this clinical form of filaminopathy of great clinical importance.

Personalized treatment of malignant tumors during pregnancy.

The combination of pregnancy and cancer is a challenge for the patient and a problematic clinical dilemma for the doctor. In this retrospective observational cohort study, we have tried to analyze our experience in the management of such patients. This review includes 41 patients with malignant neoplasms detected during pregnancy who received treatment at the Almazov National Medical Research Centre from 2015-2021. The majority of patients received treatment during pregnancy (n=26, 63.4%): chemotherapy - 19 (46.3%) (in 2 cases in combination with surgery), surgical treatment - 7 (17, 1%) patients. In most cases, delivery was at term (n=28, 68.3%). All children born at term were mature and had no growth restriction, regardless of whether the mothers received treatment during pregnancy or not. When detecting cancer during pregnancy, an immediate follow-up examination is required to assess the extent of the tumor and current fetal state. If pregnancy prolongation is requested, the treatment should not be postponed, except for systemic chemotherapy in the first trimester of pregnancy, pelvic radiation at any term.

Novel coronavirus infection and Kawasaki disease.

There is a global problem of increment of the number of children with clinical features that mimic Kawasaki Disease (KD) during the ongoing Coronavirus Disease 2019 (COVID-19) pandemic. The disease was first reported by Tomisaku Kawasaki, a Japanese pediatrician, in a four-year-old child with a rash and fever at the Red Cross Hospital in Tokyo in January 1961. Now Kawasaki disease is recognized worldwide. The complexity of symptoms was defined as an «acute febrile mucocutaneous lymphnode syndrome". At the moment, it is still unclear whether the coronavirus itself can lead to development of mucocutaneous lymph node syndrome. However, it is believed that COVID-19 virus infection worsens the course of Kawasaki disease, and in some cases, children affected by SARS-V-2 may develop a disease that has a clinical picture similar to Kawasaki disease.

[Left ventricular noncompaction: A clinical and morphological study].

The data of clinical, macro- and micrometric, histological, and immunohistochemical studies of the heart were analyzed in patients with left ventricular noncompaction (LVNC). Materials from 7 patients: 5 hearts of recipients after heart transplantation, one heart of a dead patient, and one endomyocardial biopsy specimen were investigated. The investigations showed that this disease was accompanied by a preponderance of a noncompact layer with its ratio to a compact layer (2.4:6.6) in the left ventricle and by myocardial hypertrophy and fibrosis in all cases, by endocardial fibroelastosis and discomplexation of muscle fibers by more than 15% of the specimen area in 6 of the 7 cases, by right ventricular hypertrabeculation and myocarditis in 5 cases, and by lipomatosis and impaired connexin 43 expression in 4 cases. Only one of the four patients was found to have MYH 7 gene mutation. The results of MRI of the extracted heart coincided with morphological findings in 100% of cases. The comparative study demonstrated that this disease had simultaneously morphological features of both LVNC and restrictive, hypertrophic, dilated cardiomyopathy. The findings may suggest that the LVNC phenotype may be formed under the influence of various modifying factors (hemodynamic and inflammatory ones).