Think Rare: Current Advances on Understanding and Treatment of X-Linked Neurodevelopmental Disorders

Neurodevelopmental disorders (NDDs) are chronic, heterogeneous, underdiagnosed conditions estimated to affect around 1.5% of the world population. NDDs can be rare conditions characterised by severe intellectual and physical disabilities, impacting the daily life of both patients and their families. Over 90 genes on the X chromosome have been linked to NDDs and this Research Topic will be dedicated to highlight current advances on the understanding and treatment of these conditions. Indeed, despite a relatively good knowledge about the clinical picture of many of these disorders, therapeutic development is still limited by insufficient data on gene regulation mechanisms, protein function, and pathogenesis. In addition, successful therapeutic approaches strongly rely on the development and availability of preclinical, translational endpoints and non-invasive biomarkers to accelerate clinical testing. A patient-centric approach based on continuous interchange of information with the patient community is the key to achieving rapid development of new treatments.



This Research Topic aims to outline advancements of the research about X-linked NDDs at multiple levels, welcoming original research and review articles focusing on, but not limited to, the following sub-themes:

(i) Natural history studies on X-linked NDDs or phenotypic analyses highlighting the overlap/heterogeneity of these disorders;

(ii) Novel insights into genes, regulatory mechanisms, proteins and cellular processes that provide guiding principles for the conceptualization of genes-brain-phenotype associations in X-linked NDDs;

(iii) Preclinical and clinical research on X-linked NDDs that explores molecules, cells and brain circuits underlying the pathophysiology;

(iv) Multi-level and translational neurophysiological, neuroimaging, behavioral measures and their combination with genetic and biochemical analysis for diagnosis, patient stratification, assessment of disease progression and quantification of therapeutic efficacy in X-linked NDDs;

(v) Pharmacological or non-pharmacological studies that investigates potential treatment options for X-linked NDDs.



Given the rarity of most X-linked NDDs, these editors also want to make this Research Topic an opportunity to increase the public awareness, inviting the submission of Opinion and Perspective articles to advocate for more support for families, early intervention through newborn screening and more funding for critical research. Adding representatives of the patient community as co-authors of the submitted manuscripts is encouraged.