Abstracts

Rationale: CACNA1A-Neurodevelopmetal Disorders (CACNA1A-NDD) represent a spectrum of neurological disorders including hemiplegic migraine, episodic ataxia, epilepsy, intellectual disability, and developmental delay, occurring at varying levels of severity. Disease concept models provide a formal framework to capture the lived experiences of individuals with CACNA1A-NDD. This expanded understanding of the disorder reveals treatment gaps, designs natural history studies, and helps identify potential endpoints for clinical trials.

Methods: Virtual qualitative interviews were conducted with 18 caregivers discussing 17 individuals with CACNA1A-NDD. Interviews were also conducted with four experienced healthcare providers and two educators. Interviews were systematically coded using a coding schematic designed for neurodevelopmental disorders on the Dedoose platform. Disease concepts were organized into four overarching categories: symptoms, individual impacts, caregiver impacts, and modifying factors.

Results: Most symptoms reported in the interviews aligned with those previously published, such as seizures, hypotonia, and developmental delay. Other symptoms of concern discussed by caregivers, such as sleep disorders (n=14), behavior (n=14), and gastrointestinal issues (n=11), have not been explored in depth in the medical literature. Symptom impacts on individuals in daily living and self-care abilities included needing assistance with toileting, bathing, and mobility. Caregivers reported the need for frequent appointments (n=14) and hospitalizations (n=9), physical (n=17), speech and occupational therapies (n=16), and academic accommodations (n=15). All caregivers cited anxiety and stress, mostly due to fear about their child’s future and the chance of disease regression/progression. Interviews described extensive caregiver requirements, as well as emotional and financial impacts for families impacted by CACNA1A-NDD. Advocacy (n=17) and time needed for care (n=14) were the caregiver requirements highly reported. Caregivers described financial impacts such as costs for home modifications and a reduced capacity for a parent to work. Important modifying factors that reduced disease impacts included consistent contact with reliable and knowledgeable healthcare providers and support from family and community, including the CACNA1A Foundation. The healthcare provider and educator interviews reiterated caregiver-reported symptoms, reflected the need for therapies in school and clinical settings, and recognized the need for caregivers to take on the role of advocacy and the emotional burden on caregivers.


Conclusions: CACNA1A-NDDs cover a wide range of disease concepts, mirroring the complexity of the disease. The symptoms, including some previously underreported, and impacts of the disease through the eyes of caregivers, healthcare providers, and educators have been mapped out. The insight gained from these data can help guide clinical care management, treatment development, and better clinical trial design to accelerate the path toward CACNA1A-specific therapies.

Funding: Funding was provided by the Orphan Disease Center and COMBINEDBrain.