Young onset or familial neurodegeneration starting in adulthood with a likely monogenic cause, including:
1. Unexplained dementia where acquired causes (e.g. stroke, tumour) have been excluded AND
a. Age at onset <55 years, OR b. First or second degree relative with MND/ALS (cross reference to point 3 below), OR c. Neurological features suggestive of a monogenic disorder where cognitive impairment is part of a wider phenotype, OR d. Family history highly suggestive of a monogenic cause for dementia for example one or more first or second degree relatives with dementia onset <65y where the type of dementia is the same as the proband. NOTE a family history of dementia of uncertain or mixed type where onset is predominantly over 65y is unlikely to represent a monogenic disorder. 2. Parkinson’s disease or complex Parkinsonism a. Age at onset <50 years, OR b. First degree relative affected at <50 years, OR c. Complex features such as spasticity, gaze palsy, early dementia, early bulbar failure, dyspraxia, ataxia, postural hypotension, cortical sensory loss, brain iron accumulation on MRI brain 3. Amyotrophic lateral sclerosis (ALS) with or without frontotemporal dementia a. Evidence of lower motor neuron (LMN) degeneration by clinical, electrophysiologic or neuropathologic examination, AND b. Evidence of upper motor neuron (UMN) degeneration by clinical examination, AND c. Progressive course, AND e. No evidence of other aetiology 4. Cerebral amyloid angiopathy (CAA) a. Age of onset < 50 years OR b. Family history of haemorrhagic stroke (intracerebral haemorrhage or convexity subarachnoid haemorrhage) or dementia AND c. Clinical presentation in keeping with CAA i.e. transient focal neurological episodes (“amyloid spells”), intracerebral haemorrhage, convexity subarachnoid haemorrhage, cognitive impairment, dementia AND d. Radiological features consistent with CAA i.e. two or more strictly lobar haemorrhagic lesions on blood sensitive MRI, which can include intracerebral haemorrhage, cerebral microbleeds, cortical superficial siderosis or convexity subarachnoid haemorrhage OR e. Other investigations supportive of amyloid-beta deposition within the central nervous system e.g. amyloid-PET imaging, CSF amyloid-beta measures, brain biopsy Referrals for testing will be triaged by the Genomic Laboratory; testing should be targeted at those where a genetic or genomic diagnosis will guide management for the proband or family.

Young onset or familial neurodegeneration starting in adulthood with a likely monogenic cause, including:
1. Unexplained dementia where acquired causes (e.g. stroke, tumour) have been excluded AND
a. Age at onset <55 years, OR b. First or second degree relative with MND/ALS (cross reference to point 3 below), OR c. Neurological features suggestive of a monogenic disorder where cognitive impairment is part of a wider phenotype, OR d. Family history highly suggestive of a monogenic cause for dementia for example one or more first or second degree relatives with dementia onset <65y where the type of dementia is the same as the proband. NOTE a family history of dementia of uncertain or mixed type where onset is predominantly over 65y is unlikely to represent a monogenic disorder. 2. Parkinson’s disease or complex Parkinsonism a. Age at onset <50 years, OR b. First degree relative affected at <50 years, OR c. Complex features such as spasticity, gaze palsy, early dementia, early bulbar failure, dyspraxia, ataxia, postural hypotension, cortical sensory loss, brain iron accumulation on MRI brain 3. Amyotrophic lateral sclerosis (ALS) with or without frontotemporal dementia a. Evidence of lower motor neuron (LMN) degeneration by clinical, electrophysiologic or neuropathologic examination, AND b. Evidence of upper motor neuron (UMN) degeneration by clinical examination, AND c. Progressive course, AND e. No evidence of other aetiology 4. Cerebral amyloid angiopathy (CAA) a. Age of onset < 50 years OR b. Family history of haemorrhagic stroke (intracerebral haemorrhage or convexity subarachnoid haemorrhage) or dementia AND c. Clinical presentation in keeping with CAA i.e. transient focal neurological episodes (“amyloid spells”), intracerebral haemorrhage, convexity subarachnoid haemorrhage, cognitive impairment, dementia AND d. Radiological features consistent with CAA i.e. two or more strictly lobar haemorrhagic lesions on blood sensitive MRI, which can include intracerebral haemorrhage, cerebral microbleeds, cortical superficial siderosis or convexity subarachnoid haemorrhage OR e. Other investigations supportive of amyloid-beta deposition within the central nervous system e.g. amyloid-PET imaging, CSF amyloid-beta measures, brain biopsy Referrals for testing will be triaged by the Genomic Laboratory; testing should be targeted at those where a genetic or genomic diagnosis will guide management for the proband or family.