Genetic testing in dementia‐A medical genetics perspective

Abstract

Objective When a genetic cause is suspected in a person with dementia, it creates unique diagnostic and management challenges to the treating clinician. Many clinicians may be unaware of the practicalities surrounding genetic testing for their patients, such as when to test and what tests to use and how to counsel patients and their families. This review was conducted to provide guidance to clinicians caring for patients with dementia regarding clinically relevant genetics. Methods We searched PubMed for studies that involved genetics of dementia up to March 2020. Patient file reviews were also conducted to create composite cases. Results In addition to families where a strong Mendelian pattern of family history is seen, people with younger age of onset, especially before the age of 65 years were found to be at an increased risk of harbouring a genetic cause for their dementia. This review discusses some of the most common genetic syndromes, including Alzheimer disease, frontotemporal dementia, vascular dementia, Parkinson disease dementia/dementia with Lewy bodies and some rarer types of genetic dementias, along with illustrative clinical case studies. This is followed by a brief review of the current genetic technologies and a discussion on the unique genetic counselling issues in dementia. Conclusions Inclusion of genetic testing in the diagnostic pathway in some patients with dementia could potentially reduce the time taken to diagnose the cause of their dementia. Although a definite advantage as an addition to the diagnostic repository, genetic testing has many pros and cons which need to be carefully considered first.

Young‐onset dementia diagnosis, management and care: a narrative review

“…In addition, not all genetic variants have clinical significance, and some genetic risk factors, such as the APOE risk allele, have unclear significance. Genetic counselling before testing and receiving results is therefore recommended for discussion of this complex information for families 48 …”

Contemporary techniques to the laboratory diagnosis of cognitive dysfunction (Dementia) in elderly patients.

“…Patients must provide blood, DNA that has been extracted, or saliva that will be tested for the APOE E4/E4 haplotype to participate in genetic testing for dementia [30]. Even though genetic testing for Dementia has some drawbacks, some of the most common genetic syndromes, including Alzheimer disease, frontotemporal dementia, vascular dementia, Parkinson disease dementia/dementia with Lewy bodies, and some less common types of genetic dementias, may be quickly diagnosed and timely treatment may be started with the help of genetic testing.…”

Atypical Neuropsychiatric Presentation of FTD-ALS Caused by a Pathogenic Repeat Expansion in C9orf72: A Case Report

“…It is also becoming increasingly useful to help qualify for precision treatment and to allow for opportunities to enrol into clinical trials. 24 However, as C9orf72 mutations are repeat expansions, they cannot always be accurately detected by the testing method employed for panels and whole exome sequencing. When investigating patients and choosing genetic testing for FTD-ALS, it is imperative to ensure that C9orf72 is being sequenced; it is not currently included in all targeted genetic testing panels for early onset dementia and may need to be specifically ordered with a sample sent to an alternate laboratory for Sanger Sequencing.…”