JMIR Publications

ABSTRACT

Background:

CDKL5 deficiency disorder (CDD) is an ultrarare genetic condition causing a developmental epileptic encephalopathy characterized by seizures, motor and intellectual disabilities. No disease-modifying therapies are available, and treatments focus mainly on symptom management to improve quality of life.

Objective:

The aim of the study is to better understand the burden of CDD based on family caregivers’ perception.

Methods:

The study was a cross-sectional, web-based survey comprising 40 questions for caregivers of CDD patients and focusing on sociodemographic and medical characteristics, burden of the disease, unmet needs, treatments and support. An adapted version of the EQ-5D-5L instrument was included to measure patients’ health-related quality of life as perceived by their caregivers.

Results:

A total of 132 caregivers, mostly from western parts of Europe, responded. The median age of the patients they cared for was 7.6 (IQR:2.9-12.2) years. Onset of seizures occurred early, with the median onset at 2.0 (IQR: 1.0-3.0) months of age. The median age at diagnosis was 1.2 (IQR: 0.6-4.0) years. Epilepsy (n=123, 93%) and limited communication skills (n=111, 84%) were the most commonly reported symptoms. The highest number of different types of symptoms was reported for 5- to 10-year-olds, with a median of 9.0, IQR: 7.5-10.0 symptoms. Most patients with epilepsy experienced daily seizures (n=81/123, 66%) and nearly all were on antiseizure medications (n=119/123, 97%). A minority was on a ketogenic diet (n=21/123, 17%) or had vagus nerve stimulation (n=14/123, 11%). The care received was multidisciplinary. Compared to younger patients, adults (n=20) had fewer medical appointments, and a smaller variety of healthcare professionals in their care team. The EQ-5D-5L, adapted for caregivers, indicated low health-related quality of life for patients, with a median global index value of 0.18 (IQR: 0.11-0.32). The most severe consequences of CDD on patients’ daily life were reported for mobility (67%, n=88), self-care (91%, n=120) and everyday activities (78%, n=103). Caregivers’ burden was also substantial, with all life aspects reportedly impacted by CDD, including professional life and financial resources (median impact ratings of 9.0/10 and 7.0/10 respectively). Access to support and care varied depending on location. Caregivers outside Europe, mostly from Turkey and Latin America, reported longer time between first seizure and diagnosis (26.5 months, IQR: 3.2-47.0) compared to European caregivers (11 months, IQR: 5.0-45.0). They also reported a higher impact of CDD on their financial resources (10/10) compared to Europeans (6/10) and greater challenges in covering costs.

Conclusions:

The study elucidated valuable insights on symptoms and burden of disease for CDD. This burden was quantitatively characterized with the EQ-5D-5L for the first time and was perceived as substantial by family caregivers. Discrepancies between geographic regions and age groups were highlighted, especially regarding available support and access to resources and care.