The Management of Bone Defects in Rett Syndrome.

Abstract

Rett syndrome (RS) is a rare neurodevelopmental disorder primarily caused by mutations in the X-linked methyl-CpG binding protein 2 (MECP2) gene, responsible for encoding MECP2 which plays a pivotal role in regulating gene expression. The neurological and non-neurological manifestations of RS vary widely in severity depending on the specific mutation type. Bone complications, mostly scoliosis but also osteoporosis, hip displacement, and a high rate of fractures, are among the most prevalent non-neurological comorbidities observed in girls with RS. Low bone mineral density (BMD) is primarily due to a slow rate of bone formation due to dysfunctional osteoblast activity. The use of anticonvulsants, immobilization, low physical activity, poor nutrition, and inadequate vitamin D intake all significantly hamper skeletal maturation and the accumulation of bone mass in RS girls, making them more susceptible to fragility fractures. In RS patients, the upper and lower limbs are the most common sites for fractures which are due to both a reduced BMD and a diminished bone size. This review summarizes the knowledge on risk factors for fragility fracture in patients with RS and proposes a potential diagnostic and therapeutic pathway to enhance low BMD and mitigate the risk of fragility fractures. In particular, this review focused on the importance of clinical and instrumental evaluation of bone status as a basis for adequate planning of nutritional, pharmacological, and surgical interventions to be undertaken. Additionally, the management of bone defects in individuals with RS should be customized to meet each person's specific needs, abilities, and general health.