CLINICAL AND GENETIC CHARACTERISTICS OF THE FIRST RUSSIAN PATIENT WITH BEER–STEVENSON SYNDROME CAUSED BY A MUTATION IN THE FGFR2 GENE

Beare–Stevenson cutis gyrata syndrome (BSS) is a rare autosomal dominant syndrome from the craniosynostosis group caused by mutations in the FGFR2 gene. To date, 25 patients with BSS have been described, most of whom died in infancy as a result of respiratory disorders due to upper airway abnormalities. All children with BSS from birth have specific skin abnormalities in the form of skin convolutions (cutis gyrata), resembling the convolutions of the brain. The protein product of the FGFR2 gene is the fibroblast growth factor tyrosine kinase receptor, which can be synthesized by alternative splicing in two isoforms expressed in ectodermal and mesenchymal tissues. In the previously described cases of BSS two missense mutations in the FGFR2 gene were identified: c.1124A>G and c.1115C>G, which lead to p.Tyr375Cys and p.Ser372Cys amino acid substitutions and affect the function of both isoforms, which causes variability in clinical manifestations with this syndrome. The etiological factor of most hereditary syndromes of craniosynostosis is a mutation in the FGFR2 gene, so their clinical manifestations largely overlap, which can lead to an erroneous diagnosis, make it difficult to predict the course of the disease and patient treatment tactics. Objective of the study: tto describe the clinical and genetic characteristics of the first Russian patient with BSS caused by a mutation in the FGFR2 gene (NM_00141.5): c.1124A>G (p.Tyr375Cys) in a heterozygous state that occurred de novo in the germ cell of one of the parents. The diagnosis was established by screening for mutations in the FGFR1, FGFR2, FGFR3 genes by Sanger sequencing. The existence of polymorphism of clinical manifestations in BSS has been shown. Major clinical features included multisuture craniosynostosis with a trefoil skull configuration, proptosis, cutis gyrata skin changes, acanthosis nigricans, prominent umbilical stump, neonatal teeth, hydrocephalus, choanal atresia, airway obstruction with increased granulation after tracheostomy and tracheal malformations, anterior ectopic anus, conductive hearing loss, developmental delay. Observing the results of studying the features of clinical manifestations in the proband with BSS and analyzing the literature data, helped make a conclusion about the need for differential diagnosis of BSS with various hereditary syndromes and craniosynostosis. Molecular genetic analysis may be used to confirm the diagnosis of BSS. Conclusion: early diagnosis of BSS affects treating tactics of patients and reduces the risk of complications resulting from trachea abnormalities leading to their early mortality.