Kayani Saima, BordesEdgar Veronica, Lowden Andrea, Nettesheim Emily R, Dahshi Hamza, Messahel Souad, Minassian Berge A, Greenberg Benjamin M
Department of Pediatrics, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX, 75390, USA.
Children's Health Dallas, Dallas, TX, USA.
Orphanet J Rare Dis. 2024 Dec 19;19(1):468. doi: 10.1186/s13023-024-03448-8.
This study evaluated the clinical characteristics of neuronal ceroid lipofuscinosis type 7 or CLN7 disease spectrum to characterize the clinical, electrophysiologic and neuroimaging phenotypes.
We performed a single-center cross sectional data collection along with retrospective medical chart review in patients with a genetic diagnosis of CLN7. This study received ethical approval by the University of Texas Southwestern Medical Center Institutional Review Board. A total of 8 patients were included between the ages of 4 to 6 years. All patients had a genetic diagnosis of CLN7 with homozygous or compound heterozygous mutations in the MFSD8 gene. The information collected includes patient demographics, developmental history, neurological events including seizures and neurodevelopmental regression along with further evaluation of brain magnetic resonance imaging and electrophysiological findings. The clinical phenotype is described through cross sectional and retrospective data collection and standardized tools assessing quality of life and functional skills.
Our findings in this cohort of CLN7 patients indicated that development is initially normal with onset of clinical symptoms as early as two years of age. Language problems were noted prior to or at the onset of seizures in all cases. Gait problems were noted prior to seizure onset in 3 of 8 patients, and at or within 6 months after the onset of seizures in 5 of 8 patients. All patients followed a progressive course of language, motor, and neurocognitive deterioration. Congruent with the medical history, our patients had significantly low scores on adaptive abilities. Natural history data such as this can be used to support future clinical trial designs.
This study provides a comprehensive description of CLN7 disease, highlighting clinical data alongside standardized neuropsychological assessments, neuroimaging, and electrophysiologic data. It emphasizes the value of importance of standardized tools for understanding disease phenotype and their potential use as endpoints in future clinical trials. The findings established can provide a baseline for developing future prospective natural history studies and potential therapeutic clinical trials.
本研究评估了7型神经元蜡样脂褐质沉积症（CLN7）疾病谱的临床特征，以明确其临床、电生理和神经影像学表型。
我们对经基因诊断为CLN7的患者进行了单中心横断面数据收集，并回顾了其病历。本研究获得了德克萨斯大学西南医学中心机构审查委员会的伦理批准。共纳入8例年龄在4至6岁之间的患者。所有患者均经基因诊断为CLN7，其MFSD8基因存在纯合或复合杂合突变。收集的信息包括患者人口统计学资料、发育史、神经系统事件（包括癫痫发作和神经发育倒退），以及对脑磁共振成像和电生理结果的进一步评估。通过横断面和回顾性数据收集以及评估生活质量和功能技能的标准化工具来描述临床表型。
我们在这组CLN7患者中的研究结果表明，患者最初发育正常，临床症状最早在两岁时出现。所有病例在癫痫发作之前或发作时均出现语言问题。8例患者中有3例在癫痫发作之前出现步态问题，8例患者中有5例在癫痫发作时或发作后6个月内出现步态问题。所有患者均出现语言、运动和神经认知功能的进行性衰退。与病史一致，我们的患者在适应能力方面得分显著较低。这样的自然史数据可用于支持未来的临床试验设计。
本研究全面描述了CLN7疾病，突出了临床数据以及标准化神经心理学评估、神经影像学和电生理数据。它强调了标准化工具对于理解疾病表型的重要性及其在未来临床试验中作为终点指标的潜在用途。所确立的研究结果可为开展未来前瞻性自然史研究和潜在的治疗性临床试验提供基线。
