Presentation: Adult with suspected frontotemporal dementia

A 62-year-old man presents to the memory clinic with progressive changes in personality over the past year. He is increasingly disinhibited and has made inappropriate remarks to friends and family. His wife says that he is apathetic and disinterested and that he no longer engages in his usual activities; his cigarette intake has also steadily increased. An MRI head shows atrophy in predominantly the frontal and temporal lobes. Cognitive testing reveals disproportionate deficits in executive function and planning.

• About 10%–20% of frontotemporal dementia (FTD) cases are attributable to a single gene variant.
• A good family history is important to establish if the pattern of the disease is consistent with a heritable form.
• A variant in the C9orf72 gene, as well as being the most common genetic cause for familial FTD, is also the most common genetic cause in motor neurone disease; some patients can present with symptoms of both conditions.
• There is currently no recommendation that a person with FTD should undergo genomic testing on the basis of that diagnosis alone. Eligibility for genomic testing is available, however, to those with an FTD diagnosis and one or more of the following:
  • age of onset before 55 years of age; and/or
  • a family history suggestive of a monogenic cause for dementia; for example, one or more first- or second-degree relatives with the same diagnosis or phenotype; and/or
  • a first- or second-degree relative with motor neurone disease; and/or
  • neurological features suggestive of a monogenic disorder where cognitive impairment appears to be part of a wider phenotype.
    • Note that a person with a diagnosis of amyotrophic lateral sclerosis (ALS)/motor neurone disease will also be eligible for genomic testing, with or without a diagnosis of FTD.
• Genomic testing can potentially be used early in the diagnostic process to accelerate definitive diagnosis in a sometimes indistinct or uncharacteristic presentation.
• Where a genetic cause has been identified in an affected individual, genetic counselling and, potentially, predictive (presymptomatic) testing for at-risk relatives can be accessed via the local clinical genetics service.

• Take the patient’s family history. This should include a history of at least three generations (including children, siblings, parents and grandparents), any dementias or other neurological disorders in those individuals, as well as subtypes and ages of presentation.
• Discuss with the patient and, where appropriate, their relative/advocate, the possibility the possibility of a genetic cause of dementia, the availability of testing and the implications of different outcomes. This should include the possibility of incidental findings and the identification of alternative dementia syndromes from genomic testing.
• Consult the National Genomic Test Directory. From here, you can access the rare and inherited disease eligibility criteria document for information about individual tests and their associated eligibility criteria. You can also access a spreadsheet containing details of all available tests.
  • For information about how to arrange testing in Wales, Scotland or Northern Ireland, see our dedicated Knowledge Hub resource.
• To find out which genes are included on different gene panels, see the NHS Genomic Medicine Service (GMS) Signed Off Panels Resource.
• R58 is a panel that looks at more than 120 genes known to cause adult-onset neurodegenerative conditions, including Parkinsonism and motor neurone disease as well as dementia syndromes.
  • The test uses whole genome sequencing (WGS), though only genes known to cause adult-onset neurodegenerative conditions are analysed.
  • It also includes short tandem repeat (STR) testing for a number of conditions, including Huntington disease, spinal and bulbar muscular atrophy (also known as Kennedy disease) and C9orf72-related FTD and motor neurone disease.
• As R58 is undertaken using WGS, you will need to:
  • complete an NHS GMS test order form with details of the affected individual (proband) and their parents where available, including details of the phenotype (using human phenotype ontology (HPO) terms) and the appropriate panel name(s) with associated R number (see How to complete a test order form for WGS for support);
  • complete an NHS GMS record of discussion (RoD) form for each person being tested – (see How to complete a RoD form for support); and
  • obtain a consultee form signed by an appropriate relative or advocate if an adult patient does not have capacity to consent to genomic testing.
• For the test outlined above, an EDTA sample (purple-topped tube) is required.
• Information about patient eligibility and test indications were correct at the time of writing. When requesting a test, please refer to the National Genomic Test Directory to confirm the right test for your patient.

For clinicians

• GeneReviews: MAPT-Related Frontotemporal Dementia
• Genomics England: NHS Genomic Medicine Service (GMS) Signed Off Panel Resource
• Genomics England: PanelApp
• NHS England: National Genomic Test Directory
• Practical Neurology: Genetics of Dementia

For patients

• Rare Dementia Support