THE PATTERN OF SILVER-RUSSELL SYNDROME: OWN OBSERVATION

Abstract

Silver-Russell syndrome (SRS) –is an orphan disease characterized by intrauterine and postnatal growth retardation. Children have special phenotypes, difficulties in feeding, the threat of insulin resistance, hypoglycemia, and accelerated sexual development. Aim: Increasing the effectiveness of SRS diagnosis based on the study of the features of the clinical and genetic course. Material and Methods: Clinical examination, blood tests, biochemistry, genetic tests, polymer chain reactions, and ultrasound examination have been carried out. Results: The child, 5 years old, was born from 2nd full-term pregnancy at 37 weeks, 2nd cesarean delivery with a body weight of 1900 g, height of 46 cm, head circumference of 30 cm, and chest circumference of 27 cm. Apgar scored 6/7 points. Neonatal adaptation disorders, intrauterine development, symmetrical shape, risk of hemolytic disease of the newborn according to the Rhesus factor (total bilirubin 190.0 μmol/l). The child had a special phenotype: asymmetry of the body with a relative increase in head circumference, a small triangular face with a protruding forehead, a narrow chin, a small jaw, and curvature of the 5th finger. From birth, insufficient body weight gain was observed (60 g per week, 400 g from birth in 6 weeks), which was explained by physiological vomiting and lactase deficiency (homozygous carrier of genotype C/C during PCR analysis). Body weight at the age of 1 year 5.200 g, height 63 cm, at the age of 5 years body weight 10.2 kg, height 91 cm. The child had heightened intellectual and psychological development. For the sake of differential diagnosis, a study was conducted for the presence of Gaucher’s disease (the result was negative). The results of immunologic tests: IgA 0.77 g/l, tTgIgA< 2.0 units/ml, and tTgIgG 0.05 denied the presence of celiac disease. Clinical diagnosis was established according to the Netchine-Harbison scoring system (NH-CSS), which consists of 6 clinical criteria of NH-CSS. Gene sequencing revealed changes in the variant of uncertain significance SLK25A15, the genetic significance of which is unknown, which did not allow to confirm the diagnosis. Invitae Chromoso-mal Microarray Analysis of genome research on microdeletions (duplications) revealed, with a normal female genomic profile, uniparental dysfunction with two areas of homozygosity ROH>5Mb (GRCh370) in chromosome 20: 20q13-p12.3(1-6690101; 6.69Mb and 20q13.32- q13.33(57394420- 63025520); 5.63 Mb. This change is characterized as a SRS variant, which created the basis for the diagnosis. Therefore, the child has a genetically confirmed diagnosis of SRS and congenital lactose intolerance. Somatotropic hormone (Omnitrop) was prescribed at a dose of 0.6 mg/day continuously. Conclusions: 1. The child’s SRS diagnosis was established on the basis of phenotype data, slow weight gain and growth, genetic research data, and the exclusion of the possibility of other conditions with the impaired physical development of the child. 2. The child needs a multidisciplinary approach to observation and treatment by a pediatrician or family doctor, endocrinologist, geneticist, nutritionist, surgeon, and gynecologist.