Ciliopathies comprise a group of complex disorders, with involvement of the majority of organs and systems. In total, >180 causal genes have been identified and, in addition to Mendelian inheritance, oligogenicity, genetic modifications, epistatic interactions and retrotransposon insertions have all been described when defining the ciliopathic phenotype. It is remarkable how the structural and functional impairment of a single, minuscule organelle may lead to the pathogenesis of highly pleiotropic diseases. Thus, combined efforts have been made to identify the genetic substratum and to determine the pathophysiological mechanism underlying the clinical presentation, in order to diagnose and classify ciliopathies. Yet, predicting the phenotype, given the intricacy of the genetic cause and overlapping clinical characteristics, represents a major challenge. In the future, advances in proteomics, cell biology and model organisms may provide new insights that could remodel the field of ciliopathies.

Colorectal cancer (CRC) arises through a combination of genetic and epigenetic alterations that affect key pathways involved in tumor growth and progression. This review examines the major molecular pathways driving CRC, including Chromosomal Instability (CIN), Microsatellite Instability (MSI), and the CpG Island Methylator Phenotype (CIMP). Key mutations in genes such as APC, KRAS, NRAS, BRAF, and TP53 activate signaling pathways like Wnt, EGFR, and PI3K/AKT, contributing to tumorigenesis and influencing responses to targeted therapies. Resistance mechanisms, including mutations that bypass drug action, remain challenging in CRC treatment. This review highlights the role of molecular profiling in guiding the use of targeted therapies such as tyrosine kinase inhibitors and immune checkpoint inhibitors. Novel combination treatments are also discussed as strategies to improve outcomes and overcome resistance. Understanding these molecular mechanisms is critical to advancing personalized treatment approaches in CRC and improving patient prognosis.

Lung cancer, a malignant neoplasm originating from the epithelial cells of the lung, is characterized by its aggressive growth and poor prognosis, making it a leading cause of cancer-related mortality globally

Background: Epilepsy, particularly early-onset and drug-resistant forms, presents a significant challenge in pediatric neurology. Inborn errors of metabolism are increasingly recognized as important contributors to these types of epilepsy. Timely diagnosis and treatment are crucial in preventing irreversible metabolic damage and improving clinical outcomes in CAD deficiency. This condition is a progressive and severe metabolic disorder caused by biallelic deleterious variants in CAD gene, and is characterized by long seizures, psychomotor regression, and dyserythropoietic anemia. Methods: In this paper, we present four new cases of EIEE-50, emphasizing the importance of early, specific therapeutic interventions. Results: Oral uridine 100 mg/kg/day was administrated with improvement of motor and cognitive function as well as immediate seizures control. Conclusions: Our findings underscore the potential for improved outcomes of EIEE-50 trought timely diagnosis and targeted treatment strategies, reinforcing the role of uridine supplementation as a promising therapeutic approach.

Background: Pediatric-onset multiple sclerosis (POMS) is a rare and heterogeneous condition, with clinical features, progression, and therapeutic response varying significantly according to age at onset. Early-onset MS (12 years) forms. Methods: We conducted a retrospective analysis of medical records from 120 pediatric patients diagnosed with MS at a tertiary neurology center between 2018 and 2024. Patients were grouped by age at onset and assessed for clinical presentation, number and timing of relapses, EDSS scores, imaging findings, and treatment patterns. Results: Early-onset MS was associated with atypical symptoms, delayed diagnosis, more frequent relapses, and multifocal brainstem and cerebellar involvement. The diagnosis was significantly delayed in younger children compared to adolescents. EDSS scores tended to remain stable in the first 2–3 years, but early-onset patients showed a notable decline after the fourth year. While most patients received disease-modifying therapies, high-efficacy agents were underused due to age-related restrictions. Intermediate-onset patients presented overlapping features of both early and late-onset MS and had the highest proportion of fully preserved motor function (EDSS 0) at the end of follow-up. MRI findings revealed more extensive and confluent lesions in younger patients, particularly in the first two years after onset. Conclusions: Age at disease onset is a key determinant of clinical course and treatment response in pediatric MS. Early recognition and timely initiation of appropriate therapy—especially high-efficacy agents—may improve outcomes and reduce long-term disability. Further multicenter studies with standardized imaging and cognitive assessment protocols are needed to optimize care for this vulnerable population.

This article provides a comprehensive overview of lung cancer from a genetic perspective, emphasizing the molecular pathways involved in its pathogenesis. This review presents the genetic syndromes and key genomic variations, including alterations and instabilities, that contribute to tumor development and progression. Furthermore, advancements in genomic testing, such as liquid biopsy, are explored, highlighting their utility in early diagnosis, prognostic evaluation, and personalized treatment strategies. The role of biomarkers in informing therapeutic decisions and optimizing patient outcomes is also examined, offering insights into their potential to refine clinical interventions. This review aims to enrich the understanding of the genetic landscape of lung cancer, providing insights that may lead to improved diagnostic and therapeutic approaches.