Identification of the heterozygous CACNA1D variant R390H. (a) Pedigree of the family with a combined clinical phenotype of cardiac and extra-cardiac symptoms with a heterozygous CACNA1D variant (p.Arg930His; shortly: R930H) and autosomal dominant syndromic form of SND and epilepsy. Men are denoted by squares, woman by circles. Filled symbols represent clinically affected family members; N indicates family members without a diagnosis of SND or epilepsy, + presence of the heterozygous variant R930H, − absence of the heterozygous variant R930H, 0 not tested. The proband is indicated by an arrow. Characteristics of cardiac and neurologic phenotypes are indicated below (SND, sinus node dysfunction; AVB, atrio-ventricular block; Epil., epilepsy; sEpil., suspected epilepsy; ADHD, attention deficit hyperactivity disorder). (b) ECG of proband (III:1) at age 5 years with documented sinus arrest, and (c) EEG of 3 CACNA1D variant carriers demonstrating occurrence of sharp waves with different localization. Above: EEG of family member III:I at the age of five shows occipital sharp waves (P3-O1) and bulbus artifacts (Fp1 and Fp2). Middle: EEG of family member III:2 at the age of 10 with central sharp waves (Cz-Pz). Down: EEG of index case (III:1) at the age of 10 years with left frontal sharp waves (Fp1-F3). The red boxes indicate abnormal EEG changes. Fp = most frontal leads; F = frontal; C = central; p = parietal; O = occipital.