Targeted Therapy in Channelopathies

Next-generation sequencing techniques in diagnostic setting may lead to an early genetic diagnosis in diseases characterized by high phenotypic and genetic heterogeneity. An early genetic diagnosis is important because it prevents unnecessary investigations, allows appropriate counseling of relatives, and, in rare cases, it is fundamental since it paves the way for specific treatments. We report on three patients referred for the diagnostic workup of an early onset encephalopathy. Patient 1 is a 10 months old male who presented at 28 weeks of gestation with macrocephaly, cerebral ventricular dilatation, and paroxysmal tachycardia. At birth, the clinical picture was characterized by macrocephaly, severe hypotonic-hypokinetic-apostural syndrome, hyponatremia, refractory focal seizures with burst suppression. Exome sequencing revealed a de novo missense mutation in SCN2A. The second patient is a 4 years old female child presenting a neonatal onset encephalopathy initially characterized by developmental delay and generalized jerky dyskinesias, progressively associated with cerebellar signs and, from 2 years of age, prolonged focal seizures triggered by minor head trauma. A customized gene panel for epileptic disorders disclosed a novel missense mutation in CACNA1A. The last patient presented soon after birth with focal refractory seizures that evolved to epileptic spasm at 4 months and finally to a malignant migrating partial seizures of infancy from age 9 months. A gene panel showed a de novo missense mutation in KCNT1. In all patients, the precise genetic diagnosis allowed us to start specific treatments, ameliorating the neurological picture.

No conflict of interest has been declared by the author(s).