Cerebellar Agenesis and Bilateral Polimicrogyria Associated with Rare Variants of CUB and Sushi Multiple Domains 1 Gene (CSMD1): A Longitudinal Neuropsychological and Neuroradiological Case Study.
Floriana Costanzo: Child and Adolescent Neuropsychiatry Unit, Department of Neurosciences, Bambino Gesù Children's Hospital IRCCS, Via Ferdinando Baldelli 41, I-00146 Rome, Italy. ORCID
Ginevra Zanni: Unit of Neuromuscular and Neurodegenerative Disorders, Department of Neurosciences, Bambino Gesù Children's Hospital, IRCCS, Viale di San Paolo 15, I-00146 Rome, Italy. ORCID
Elisa Fucà: Child and Adolescent Neuropsychiatry Unit, Department of Neurosciences, Bambino Gesù Children's Hospital IRCCS, Via Ferdinando Baldelli 41, I-00146 Rome, Italy. ORCID
Margherita Di Paola: Department of Clinical and Behavioral Neurology, IRCCS Santa Lucia Foundation, Via Ardeatina 306, I-00179 Rome, Italy.
Sabina Barresi: Pathology Unit, Department of Laboratories, Bambino Gesù Children's Hospital, IRCCS, Viale di San Paolo 15, I-00146 Rome, Italy. ORCID
Lorena Travaglini: Unit of Neuromuscular and Neurodegenerative Disorders, Department of Neurosciences, Bambino Gesù Children's Hospital, IRCCS, Viale di San Paolo 15, I-00146 Rome, Italy.
Giovanna Stefania Colafati: Oncological Neuroradiology Unit, Department of Imaging, Bambino Gesù Children's Hospital, IRCCS, Piazza Sant'Onofrio 4, I-00100 Rome, Italy. ORCID
Antonio Gambardella: Institute of Neurology, University Magna Græcia, I-88100 Catanzaro, Italy.
Emanuele Bellacchio: Genetics and Rare Diseases Research Division, Bambino Gesù Children's Hospital, Viale di San Paolo 15, I-00146 Rome, Italy.
Enrico Bertini: Unit of Neuromuscular and Neurodegenerative Disorders, Department of Neurosciences, Bambino Gesù Children's Hospital, IRCCS, Viale di San Paolo 15, I-00146 Rome, Italy. ORCID
Deny Menghini: Child and Adolescent Neuropsychiatry Unit, Department of Neurosciences, Bambino Gesù Children's Hospital IRCCS, Via Ferdinando Baldelli 41, I-00146 Rome, Italy. ORCID
Stefano Vicari: Child and Adolescent Neuropsychiatry Unit, Department of Neurosciences, Bambino Gesù Children's Hospital IRCCS, Via Ferdinando Baldelli 41, I-00146 Rome, Italy.
Cerebellar agenesis is an extremely rare condition characterized by a near complete absence of the cerebellum. The pathogenesis and molecular basis remain mostly unknown. We report the neuroradiological, molecular, neuropsychological and behavioral characterization of a 5-year-old girl, with cerebellar agenesis associated with parietal and peri-Sylvian polymicrogyria, followed-up for 10 years at four time points. Whole exome sequencing identified two rare variants in , a gene associated with neurocognitive and psychiatric alterations. Mild intellectual impairment, cerebellar ataxia and deficits in language, memory and executive functions, with relatively preserved adaptive and psychopathological domains, were initially showed. Phonological awareness and verbal memory declined at 11 years of age, and social and anxiety problems emerged. Adaptive and psychopathological characteristics dramatically worsened at 15 years. In summary, the developmental clinical outcome showed impairment in multiple cognitive functions in childhood, with a progressive decline in cognitive and adaptive abilities and the emergence of psychopathological symptoms in adolescence. The observed phenotype could be the result of a complex interplay between cerebellar abnormality, brain malformation and the relations with variants. These findings may provide insights into the developmental clinical outcomes of a co-occurrence between rare brain malformation and rare genetic variants associated to neurodevelopmental disorders.
