Introduction: Sleep is a fundamental biological function critical for physical and mental health. Chronic sleep disturbances can significantly impair cognitive, emotional, and social functioning, leading to deficits in attention, alertness, and executive function, alongside increased irritability, anxiety, and depression. For pediatric patients, such disturbances pose additional concerns, potentially disrupting developmental processes and quality of life for both children and their families. Objectives: Emerging evidence suggests a correlation between neurofibromatosis type 1 (NF1) and an increased prevalence of sleep disorders in children. NF1, a genetic condition affecting multiple body systems, including the nervous system, may predispose children to sleep disturbances due to its neurodevelopmental and behavioral impacts. This observational case–control study aimed to explore the association between NF1 and sleep disorders in pediatric patients, comparing the prevalence and patterns of sleep disturbances between NF1 patients and healthy controls. Patients and Methods: The study included 100 children aged 2–12 years, divided into two groups: 50 with NF1 (case group) and 50 children belonging to the control group. NF1 patients were recruited from the Unit of Rare Diseases of the Nervous System in Childhood at the Policlinico “G. Rodolico—San Marco” University Hospital in Catania. Data were collected using a questionnaire completed by parents, assessing parasomnias, breathing-related sleep disorders, and other behavioral and physiological disturbances; these data were compared to a sleep assessment performed using an Apple Watch Ultra. Results: NF1 patients exhibited a significantly higher prevalence of sleep disorders than controls. Notable differences included increased nocturnal hyperhidrosis (48% vs. 10%), bruxism (48% vs. 28%), restless legs syndrome (22% vs. 4%), frequent nighttime awakenings (22% vs. 8%), and sleep paralysis (12% vs. 0%). A finding of poorer sleep quality also emerged from the results of sleep analysis using an Apple Watch Ultra. Conclusions: These findings confirm an elevated risk of sleep disorders in children with NF1, emphasizing the importance of early identification and management to improve quality of life and mitigate cognitive and behavioral impacts. Further research is essential to understand the mechanisms underlying these associations and develop targeted interventions for this population.

CTNND1 is a gene located in 11q12.1, encoding for p120 catenin, a protein involved in maintaining adherent junctions, regulating the epithelial–mesenchymal transition, and transcriptional signaling of different cellular pathways. Pathogenic variants in CTNND1 are classically associated with isolated cleft palate and Blefaro‐cheilo‐dontic syndrome, an autosomal dominant condition characterized by abnormalities of the eyelid. Considering different signs and symptoms associated first with Blefaro‐cheilo‐dontic syndrome and later specifically with CTNND1, Ahlaratani and colleagues proposed a wider developmental role for CTNND1 than previously described, associating a broader phenotypic spectrum. This report describes a prenatal case in which a CTNND1 pathogenic variant and reverse phenotyping allowed a diagnosis of Blefaro‐cheilo‐dontic syndrome associated with characteristics never related to Blefaro‐cheilo‐dontic syndrome or CTNND1, such as hydrocephalus. This report is the first detailed fetal case of Blefaro‐cheilo‐dontic syndrome, and the new feature reported is consistent with CTNND1 developmental role and may add new insights into the phenotype spectrum that is being defined.

Behçet's syndrome is a systemic inflammatory disorder of unknown origin, presenting with diverse symptoms such as recurrent oral and genital ulcers, skin lesions, and uveitis, and can impact multiple organ systems. Diagnosis relies primarily on clinical evaluation due to the lack of specific diagnostic tests. Management requires a multidisciplinary approach to control inflammation and alleviate symptoms, utilizing treatments like corticosteroids, immunosuppressive agents, and biological therapies. The higher prevalence of Behçet's syndrome along the Silk Road points to significant environmental and genetic influences. Despite progress in understanding its clinical manifestations and treatment options, the underlying mechanisms of the disease remain unclear. Future research is crucial to uncover the disease's pathophysiology and refine treatment strategies, aiming to prevent severe complications such as blindness and neurological impairment. This comprehensive review explores the clinical features, genetic background, and management strategies for Behçet's syndrome, highlighting the potential of precision medicine to improve patient care.