Back to Search
Start Over
The genetic landscape of intellectual disability and epilepsy in adults and the elderly: a systematic genetic work-up of 150 individuals
- Source :
- Genetics in Medicine
- Publication Year :
- 2021
- Publisher :
- Elsevier BV, 2021.
-
Abstract
- Purpose Genetic diagnostics of neurodevelopmental disorders with epilepsy (NDDE) are predominantly applied in children, thus limited information is available regarding adults or elderly. Methods We investigated 150 adult/elderly individuals with NDDE by conventional karyotyping, FMR1 testing, chromosomal microarray, panel sequencing, and for unresolved cases, also by exome sequencing (nsingle = 71, ntrios = 24). Results We identified (likely) pathogenic variants in 71 cases (47.3%) comprising fragile X syndrome (n = 1), disease-causing copy number (n = 23), and single-nucleotide variants (n = 49). Seven individuals displayed multiple independent genetic diagnoses. The diagnostic yield correlated with the severity of intellectual disability. Individuals with anecdotal evidence of exogenic early-life events (e.g., nuchal cord, complications at delivery) with alleged/unproven association to the disorder had a particularly high yield of 58.3%. Screening for disease-specific comorbidities was indicated in 45.1% and direct treatment consequences arose in 11.8% of diagnosed individuals. Conclusion Panel/exome sequencing displayed the highest yield and should be considered as first-tier diagnostics in NDDE. This high yield and the numerous indications for additional screening or treatment modifications arising from genetic diagnoses indicate a current medical undersupply of genetically undiagnosed adult/elderly individuals with NDDE. Moreover, knowledge of the course of elderly individuals will ultimately help in counseling newly diagnosed individuals with NDDE.
- Subjects :
- Adult
0301 basic medicine
Pediatrics
medicine.medical_specialty
Article
Fragile X Mental Retardation Protein
03 medical and health sciences
Epilepsy
0302 clinical medicine
Intellectual Disability
Exome Sequencing
Intellectual disability
medicine
Humans
Medical diagnosis
Genetics (clinical)
Exome sequencing
Aged
business.industry
medicine.disease
FMR1
Work-up
Fragile X syndrome
030104 developmental biology
Neurodevelopmental Disorders
Karyotyping
Nuchal cord
business
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 10983600
- Volume :
- 23
- Database :
- OpenAIRE
- Journal :
- Genetics in Medicine
- Accession number :
- edsair.doi.dedup.....3cb796cf5f58cf24615373c0ca77c40e