Clinical and molecular spectrum of P/Q type calcium channel Cav2.1 in epileptic patients

BACKGROUND: Epilepsy is a neurological disorder characterized by the potential to induce seizure and accompanied by cognitive, psychological, and social consequences. CACNA1A gene is a voltage-gated P/Q-type Cav2.1 channel that is broadly expressed in the central nervous system, and the pathogenic variants within this gene may be associated with the epileptic phenotype. In the present study, we collected clinical and molecular data related to epileptic patients with CACNA1A pathogenic variants and investigated possible meaningful relationship between age at onset, neurodevelopmental disorders, type of seizures, brain imaging abnormalities, genotype, and protein domains. RESULTS: In our retrospective literature studies, from among 890 articles reviewed, a total of 90 individuals were related to epilepsy phenotype. Our findings showed that about 90 percent of patients have shown the first symptoms in childhood and teenage years and different types of neurodevelopmental disorders, such as intellectual disability, developmental arrest, and behavioral disorders, have been common findings for these patients. Further, a wide range of abnormalities have been observed in their brain imaging, and generalized seizures have been the most type of seizures in these patients. However, our data showed no specific genotype–phenotype correlation in epileptic patients with CACNA1A pathogenic alterations. CONCLUSIONS: Our study focused on epileptic phenotype in patients with CACNA1A pathogenic variants and showed a wide range of clinical and molecular heterogeneity with no specific genotype–phenotype correlation. It seems that incomplete penetrance, de-novo variants, and modifier genes are obstacles in predicting the clinical outcome. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13023-021-02101-y.