Neuronal ceroid lipofuscinoses type 7 (CLN7): a case series reporting cross sectional and retrospective clinical data to evaluate validity of standardized tools to assess disease progression, quality of life, and adaptive skills

Abstract Background This study evaluated the clinical characteristics of neuronal ceroid lipofuscinosis type 7 or CLN7 disease spectrum to characterize the clinical, electrophysiologic and neuroimaging phenotypes. Methods We performed a single-center cross sectional data collection along with retros...

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Main Authors: Saima Kayani, Veronica BordesEdgar, Andrea Lowden, Emily R. Nettesheim, Hamza Dahshi, Souad Messahel, Berge A. Minassian, Benjamin M. Greenberg
Format: Article
Language:English
Published: BMC 2024-12-01
Series:Orphanet Journal of Rare Diseases
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Online Access:https://doi.org/10.1186/s13023-024-03448-8
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author Saima Kayani
Veronica BordesEdgar
Andrea Lowden
Emily R. Nettesheim
Hamza Dahshi
Souad Messahel
Berge A. Minassian
Benjamin M. Greenberg
author_facet Saima Kayani
Veronica BordesEdgar
Andrea Lowden
Emily R. Nettesheim
Hamza Dahshi
Souad Messahel
Berge A. Minassian
Benjamin M. Greenberg
author_sort Saima Kayani
collection DOAJ
description Abstract Background This study evaluated the clinical characteristics of neuronal ceroid lipofuscinosis type 7 or CLN7 disease spectrum to characterize the clinical, electrophysiologic and neuroimaging phenotypes. Methods 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. Results 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. Conclusions 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.
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spelling doaj-art-dfad8e54cc794bf8b10c8285e66c86632025-08-20T02:31:52ZengBMCOrphanet Journal of Rare Diseases1750-11722024-12-0119111210.1186/s13023-024-03448-8Neuronal ceroid lipofuscinoses type 7 (CLN7): a case series reporting cross sectional and retrospective clinical data to evaluate validity of standardized tools to assess disease progression, quality of life, and adaptive skillsSaima Kayani0Veronica BordesEdgar1Andrea Lowden2Emily R. Nettesheim3Hamza Dahshi4Souad Messahel5Berge A. Minassian6Benjamin M. Greenberg7Department of Pediatrics, University of Texas Southwestern Medical CenterDepartment of Pediatrics, University of Texas Southwestern Medical CenterDepartment of Pediatrics, University of Texas Southwestern Medical CenterDepartment of Ophthalmology, University of Texas Southwestern Medical CenterPerot Neuroscience Translational Research Center, Peter O’Donnell Brain InstitutePerot Neuroscience Translational Research Center, Peter O’Donnell Brain InstituteDepartment of Pediatrics, University of Texas Southwestern Medical CenterDepartment of Pediatrics, University of Texas Southwestern Medical CenterAbstract Background This study evaluated the clinical characteristics of neuronal ceroid lipofuscinosis type 7 or CLN7 disease spectrum to characterize the clinical, electrophysiologic and neuroimaging phenotypes. Methods 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. Results 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. Conclusions 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.https://doi.org/10.1186/s13023-024-03448-8MFSD8Neuronal ceroid lipofuscinosisBatten diseaseRare brain disease
spellingShingle Saima Kayani
Veronica BordesEdgar
Andrea Lowden
Emily R. Nettesheim
Hamza Dahshi
Souad Messahel
Berge A. Minassian
Benjamin M. Greenberg
Neuronal ceroid lipofuscinoses type 7 (CLN7): a case series reporting cross sectional and retrospective clinical data to evaluate validity of standardized tools to assess disease progression, quality of life, and adaptive skills
Orphanet Journal of Rare Diseases
MFSD8
Neuronal ceroid lipofuscinosis
Batten disease
Rare brain disease
title Neuronal ceroid lipofuscinoses type 7 (CLN7): a case series reporting cross sectional and retrospective clinical data to evaluate validity of standardized tools to assess disease progression, quality of life, and adaptive skills
title_full Neuronal ceroid lipofuscinoses type 7 (CLN7): a case series reporting cross sectional and retrospective clinical data to evaluate validity of standardized tools to assess disease progression, quality of life, and adaptive skills
title_fullStr Neuronal ceroid lipofuscinoses type 7 (CLN7): a case series reporting cross sectional and retrospective clinical data to evaluate validity of standardized tools to assess disease progression, quality of life, and adaptive skills
title_full_unstemmed Neuronal ceroid lipofuscinoses type 7 (CLN7): a case series reporting cross sectional and retrospective clinical data to evaluate validity of standardized tools to assess disease progression, quality of life, and adaptive skills
title_short Neuronal ceroid lipofuscinoses type 7 (CLN7): a case series reporting cross sectional and retrospective clinical data to evaluate validity of standardized tools to assess disease progression, quality of life, and adaptive skills
title_sort neuronal ceroid lipofuscinoses type 7 cln7 a case series reporting cross sectional and retrospective clinical data to evaluate validity of standardized tools to assess disease progression quality of life and adaptive skills
topic MFSD8
Neuronal ceroid lipofuscinosis
Batten disease
Rare brain disease
url https://doi.org/10.1186/s13023-024-03448-8
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