Contribution of Mendelian Disorders in a Population-Based Pediatric Neurodegeneration Cohort
Rose Guo1, Frank D Mentch2, Dong Li2
1Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, PA.
Insights
Genetic testing identified the cause of neurodegenerative disorders in 60.9% of pediatric patients. This study highlights the genetic basis of these conditions and the need for further research to diagnose all affected children.
Area of Science:
- Pediatric Neurology
- Clinical Genetics
- Neurodegenerative Diseases
Background:
- Neurodegenerative disorders in children are complex and often lack a clear diagnosis.
- Identifying genetic causes is crucial for understanding disease mechanisms and guiding management.
Purpose of the Study:
- To investigate the prevalence of Mendelian causes of neurodegenerative disorders in a pediatric cohort.
- To assess the diagnostic yield of genetic evaluations in these patients.
Main Methods:
- Utilized an algorithm with ICD-9/10 codes to identify pediatric patients with neurodegenerative symptoms from a large biobank.
- Conducted manual chart reviews to abstract detailed clinical and genetic information.
Main Results:
- Out of 76 patients with a neurodegenerative phenotype, 69 were analyzed. Genetic diagnoses were established in 42 patients (60.9%), identifying 32 unique disorders.
- Common diagnoses included Rett syndrome, mitochondrial disorders, and neuronal ceroid lipofuscinoses.
- 27 patients (39.1%) remained undiagnosed despite genetic evaluation.
Conclusions:
- The study reveals the wide spectrum of genetic disorders contributing to pediatric neurodegeneration.
- Diagnosis significantly impacts clinical management, though curative treatments are often unavailable.
- A substantial proportion of patients remain undiagnosed, underscoring the need for ongoing research in pediatric neurogenetics.
Objective:
To evaluate Mendelian causes of neurodegenerative disorders in a cohort of pediatric patients.
Study Design:
Patients enrolled in the Center for Applied Genomics Biobank at the Children's Hospital of Philadelphia with neurodegenerative symptoms were identified using an algorithm that consisted of including and excluding selected International Classification of Diseases, 9th and 10th edition codes. A manual chart review was then performed to abstract detailed clinical information.
Results:
Of approximately 100 000 patients enrolled in the Center for Applied Genomics Biobank, 76 had a neurodegenerative phenotype. After chart review, 7 patients were excluded. Of the remaining 69 patients, 42 had a genetic diagnosis (60.9%) and 27 were undiagnosed (39.1%). There were 32 unique disorders. Common diagnoses included Rett syndrome, mitochondrial disorders, and neuronal ceroid lipofuscinoses.
Conclusions:
The disorders encountered in our cohort demonstrate the diverse diseases and pathophysiology that contribute to pediatric neurodegeneration. Establishing a diagnosis often informed clinical management, although curative treatment options are lacking. Many patients who underwent genetic evaluation remained undiagnosed, highlighting the importance of continued research efforts in this field.
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