Abstract
KCNT1 gene encodes the sodium-dependent potassium channel reported as a causal factor for several different epileptic disorders. The gene has been also linked with cardiac disorders and in a family to sudden unexpected death in epilepsy. KCNT1 mutations, in most cases, result in a gain of function causing a neuronal hyperpolarization with loss of inhibition. Many early-onset epileptic encephalopathies related to gain of function of KCNT1 gene have been described, most often associated with two phenotypes: malignant migrating focal seizures of infancy and familial autosomal-dominant nocturnal frontal lobe epilepsy; however, there is no clear phenotype–genotype correlation, in fact same mutations have been represented in patients with West syndrome, Ohtahara syndrome, and early myoclonic encephalopathy. Additional neurologic features include intellectual disability, psychiatric disorders, hypotonia, microcephaly, strabismus, and movement disorders. Conventional anticonvulsant, vagal stimulation, and ketogenic diet have been used in the absence of clinical benefit in individuals with KCNT1-related epilepsy; in some patients, quinidine therapy off-label has been practiced successfully. This review aims to describe the characteristics of the gene, the phenotypes related to genetic mutations with the possible genotype–phenotype correlations and the treatments proposed to date, discussing the comorbidities reported in the literature.
Neuropsychiatric Functioning in CDLS: A Detailed Phenotype and Genotype Correlation
