Amin Sam, Partridge Carol-Anne, Leonard Helen, Downs Jenny, Allvin Helen, Ficara Valentine, Pain Emilie, Korolainen Minna A
Department of Paediatric Neurology, Bristol Royal Hospital for Children, Bristol, United Kingdom.
CDKL5 UK, Bristol, United Kingdom.
JMIR Form Res. 2025 Jun 10;9:e72489. doi: 10.2196/72489.
Cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder (CDD) is an ultrarare genetic condition causing developmental epileptic encephalopathy characterized by seizures and motor and intellectual disabilities. No disease-modifying therapies are available, and treatments focus mainly on symptom management to improve quality of life.
The aim of this study was to better understand the burden of CDD based on family caregivers' perceptions.
The study was a cross-sectional, web-based survey comprising 40 questions for caregivers of patients with CDD and focusing on sociodemographic and medical characteristics, disease burden, 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.
A total of 132 caregivers, mostly from western parts of Europe, responded. The median patient age was 7.6 (IQR 2.9-12.2) years. Seizure onset 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 (123/132, 93.2%) and limited communication skills (111/132, 84.1%) were the most commonly reported symptoms. The highest number of different types of symptoms was reported for patients aged 5-9 years, with a median of 9.0 (IQR 7.5-10.0) symptoms. Most patients with epilepsy experienced daily seizures (81/123, 65.9%), and nearly all (119/123, 96.7%) were on antiseizure medications. A minority was on a ketogenic diet (21/123, 17.1%) or underwent vagus nerve stimulation (14/123, 11.4%). The care received was multidisciplinary. Compared to younger patients, adults had fewer medical appointments and a smaller variety of health care 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 lives were reported for mobility (88/132, 66.7%), self-care (120/132, 90.9%), and everyday activities (103/132, 78.0%). Caregiver 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 reported a longer time between the first seizure and diagnosis (26.5, IQR 3.2-47.0 months) compared to European caregivers (11.0, IQR 5.0-45.0 months). They also reported a higher impact of CDD on their financial resources (rating of 10/10) compared to European caregivers (rating of 6/10) and greater challenges in covering costs.
The study findings provide valuable insights on symptoms and disease burden related to 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.
细胞周期蛋白依赖性激酶样 5（CDKL5）缺乏症（CDD）是一种极为罕见的遗传性疾病，可导致发育性癫痫性脑病，其特征为癫痫发作以及运动和智力残疾。目前尚无改善病情的疗法，治疗主要集中于症状管理以提高生活质量。
本研究旨在基于家庭照料者的认知，更好地了解 CDD 的负担情况。
该研究是一项基于网络的横断面调查，包含 40 个针对 CDD 患者照料者的问题，重点关注社会人口统计学和医学特征、疾病负担、未满足的需求、治疗方法及支持情况。纳入了 EQ-5D-5L 工具的改编版本，以衡量照料者所感知的患者健康相关生活质量。
共有 132 名照料者做出回应，他们大多来自欧洲西部。患者的中位年龄为 7.6（四分位间距 2.9 - 12.2）岁。癫痫发作起病较早，中位起病年龄为 2.0（四分位间距 1.0 - 3.0）个月。诊断时的中位年龄为 1.2（四分位间距 0.6 - 4.0）岁。癫痫（123/132，93.2%）和沟通技能受限（111/132，84.1%）是最常报告的症状。5 - 9 岁患者报告的不同类型症状数量最多，中位症状数为 9.0（四分位间距 7.5 - 10.0）个。大多数癫痫患者每天发作（81/123，65.9%），几乎所有患者（119/123，96.7%）都在服用抗癫痫药物。少数患者采用生酮饮食（21/123，17.1%）或接受迷走神经刺激治疗（14/123，11.4%）。所接受的护理是多学科的。与较年轻患者相比，成年人的医疗预约次数较少，其护理团队中的医疗保健专业人员种类也较少。改编用于照料者的 EQ-5D-5L 表明患者的健康相关生活质量较低，全球指数中位值为 0.18（四分位间距 0.11 - 0.32）。CDD 对患者日常生活最严重的影响体现在行动能力（88/132，66.7%）、自我护理（120/132，90.9%）和日常活动（103/132，78.0%）方面。照料者的负担也很重，据报告 CDD 影响了生活的各个方面，包括职业生活和财务资源（中位影响评分分别为 9.0/10 和 7.0/10）。获得支持和护理的情况因地点而异。与欧洲照料者（11.0，四分位间距 5.0 - 45.0 个月）相比（11.0，四分位间距 5.0 - 45.0 个月），欧洲以外地区的照料者报告首次发作与诊断之间的时间间隔更长（26.5，四分位间距 3.2 - 47.0 个月）。他们还报告 CDD 对其财务资源的影响更大（评分 10/10），相比之下欧洲照料者的评分为 6/10，并且在支付费用方面面临更大挑战。
研究结果为与 CDD 相关的症状和疾病负担提供了有价值的见解。首次使用 EQ-5D-5L 对这种负担进行了定量描述，家庭照料者认为负担很重。突出了地理区域和年龄组之间的差异，特别是在可获得的支持以及资源和护理的获取方面。
