Spectrum of Mutations and Clinical Manifestations of Rett Syndrome in Girls from Western Ukraine

Rett syndrome is one of the most common causes of mental retardation in girls. The aim of our work was to study a spectrum of genetic heterogeneity and various clinical manifestations of Rett syndrome in girls Western Ukraine. Materials and methods: there were used clinical, molecular and genetic methods. We observed seven girls with Rett syndrome aged from 6 months to 15 years who were diagnosed and followed-up at the Institute of Hereditary Pathology, National Academy of Medical Sciences of Ukraine, Lviv for three years (2019–2021) and underwent molecular genetic analyses confirmed by next-generation sequencing. Results: In this study, patients with Rett syndrome had individual clinical heterogeneity and age variability due to different mutations. Mental retardation was not observed among siblings in families with Rett syndrome. We identified seven different pathogenic mutations among seven girls, including two deletions and one duplication of the MECP2 gene. Microcephaly was observed in two girls with MECP2 c.880C>T (p.Arg294*) and MECP2 Gain (Entire coding sequence) at birth. The following developmental disabilities were found in five girls: lack of independent sitting, lack of independent gait (regression of development). Among musculoskeletal disorders, there were diagnosed scoliosis, X-shaped deformation of the lower extremities and muscular hypotonia. A two-year-old girl with Rett syndrome, along with other clinical symptoms, had breathing problems - hyperventilation (rapid shallow breathing). Conclusions: in cases with unknown cause of delayed developmental disability and mental retardation the patients should be referred for medical genetic counselling.