Rett syndrome: think outside the (skull) box

Abstract

Rett syndrome (RTT) is a severe X-linked neurodevelopmental disorder characterized by neurodevelopmental regression between 6 and 18 months of life and associated with multi-system comorbidities. Caused mainly by pathogenic variants in the MECP2 (methyl CpG binding protein 2) gene, it is the second leading genetic cause of intellectual disability in girls after Down syndrome. RTT affects not only neurological function but also a wide array of non-neurological organs. RTT-related disorders involve abnormalities of the respiratory, cardiovascular, digestive, metabolic, skeletal, endocrine, muscular, and urinary systems and immune response. Here, we review the different aspects of RTT affecting the main peripheral groups of organs and sometimes occurring independently of nervous system defects.

State‐of‐the‐art therapies for Rett syndrome

“…However, it was not until two decades later that RTT became officially recognized after a Swedish neurologist, Bengt Hagberg, observed patients with similar symptoms and decided, with French and Portuguese colleagues, to publish an article describing the syndrome 2 . RTT alone accounts for 10% of cases of profound intellectual disability of genetic origin in females 3 . RTT is a severe developmental disorder 4,5 .…”

Sirtuins as potential therapeutic targets for mitigating OxInflammation in typical Rett syndrome: plausible mechanisms and evidence

“…However, in the last few years, a multifaceted clinical appearance with variety of co-morbidities involving other tissues and organs have been identified in RTT patients, including sleep disturbances, periodic breathing disorder, electrocardiograms with prolonged cardiac QT interval, osteopenia, endocrine alterations, gastrointestinal problems, dysphagia, recurrent infections (especially at gallbladder, urinary and respiratory tract) or unexplained augment of fever (Borloz et al 2021, Wang et al 2021. In addition, from a molecular point of view, RTT patients exhibit deregulations of signalling and metabolic pathways, such as abnormal mitochondrial bioenergetics, unbalanced redox homeostasis, perturbed lipid metabolism and compromised immune-inflammatory responses (Segatto et al 2014, Filosa et al 2015, Shulyakova et al 2017, Pecorelli et al 2020a.…”

“…Taken together, the combination of all these alterations can help to explain the complex nature of RTT, which is now increasingly considered a broad-spectrum pathology with multisystem disturbances (Borloz et al 2021).…”

Pain in Rett syndrome: a pilot study and a single case study on the assessment of pain and the construction of a suitable measuring scale

“…The clinical picture is characterized by the progressive loss of manual skills, language, anomalies or absence of movement and by the appearance of stereotypies of the hands, alterations in breathing when awake, which may include hyperventilation and frequent convulsions [5][6][7][8][9][10]. Various comorbidities are present in RTT in addition to epilepsy, such as gastrointestinal and orthopedic problems, as well as less frequent issues such as endocrinological and cardiac problems, but also liver damage, respiratory disorders, urological dysfunctions, and inflammatory diseases, which make it a very complex and multifaceted syndrome [11][12][13][14]. Rett patients may also experience pain caused by other factors such as when confined to a wheel chair, when having routine clinical examinations such as blood draws, etc.…”

“…Rett patients may also experience pain caused by other factors such as when confined to a wheel chair, when having routine clinical examinations such as blood draws, etc. According to caregivers, many of these chronic health problems cause pain and impair the quality of life of patients with RTT [12,15]. Many conditions are particularly painful, such as low bone density.…”