The cerebellum and its functional multiplicity and heterogeneity have been objects of curiosity and interest since ancient times, giving rise to the urge to reveal its complexity. Since the first hypothesis of cerebellar mere role in motor tuning and coordination, much more has been continuously discovered about the cerebellum’s circuitry and functioning throughout centuries, leading to the currently accepted knowledge of its prominent involvement in cognitive, social, and behavioral areas. Particularly in childhood, the cerebellum may subserve several age-dependent functions, which might be compromised in several Central Nervous System pathologies. Overall, cerebellar damage may produce numerous signs and symptoms and determine a wide variety of neuropsychiatric impairments already during the evolutive age. Therefore, an early assessment in children would be desirable to address a prompt diagnosis and a proper intervention since the first months of life. Here we provide an overview of the cerebellum, retracing its morphology, histogenesis, and physiological functions, and finally outlining its involvement in typical and atypical development and the age-dependent patterns of cerebellar dysfunctions.

The cerebellum plays a critical regulatory role in motor coordination, cognition, behavior, language, memory, and learning, hence overseeing a multiplicity of functions. Cerebellar development begins during early embryonic development, lasting until the first postnatal years. Particularly, the greatest increase of its volume occurs during the third trimester of pregnancy, which represents a critical period for cerebellar maturation. Preterm birth and all the related prenatal and perinatal contingencies may determine both dysmaturative and lesional events, potentially involving the developing cerebellum, and contributing to the constellation of the neuropsychiatric outcomes with several implications in setting-up clinical follow-up and early intervention.

Seizures are the most frequent neurological clinical symptoms of the central nervous system (CNS) during the neonatal period. Neonatal seizures may be ascribed to an acute event or symptomatic conditions determined by genetic, metabolic or structural causes, outlining the so-called ‘Neonatal Epilepsies’. To date, three main groups of neonatal epilepsies are recognised during the neonatal period: benign familial neonatal epilepsy (BFNE), early myoclonic encephalopathy (EME) and ‘Ohtahara syndrome’ (OS). Recent advances showed the role of several genes in the pathogenesis of these conditions, such as KCNQ2, KCNQ3, ARX, STXBP1, SLC25A22, CDKL5, KCNT1, SCN2A and SCN8A. Herein, we reviewed the current knowledge regarding the pathogenic variants most frequently associated with neonatal seizures, which should be considered when approaching newborns affected by these disorders. In addition, we considered the new possible therapeutic strategies reported in these conditions.