SUMMARY NEUROGENETICS
EXAM:
- Written + oral part
- Open questions
- Terms to explain
- Linking things
1. INTRODUCTION
➢ Broad classification of neurological diseases (with example)
➢ How to identify a (neuro)genetic disorder?
➢ Understanding of inheritance patterns and knowledge on key factors influencing them
➢ Concepts of gene identification: linkage versus genome-wide association studies
➢ Understanding of contribution of common and rare variants to neurological diseases
➢ Overview of types of disease-causing genetic variation (coding and non-coding mutations)
What are neurological disorders and how many people are affected by them?
1.1. CLASSIFICATION OF NEUROLOGICAL DISORDERS
• > 200 neurological disorders have been described
• Many classification systems exist e.g. based in clinical presentation, primary affected cell
type/ brain region temporal expression, …
o Some diseases are part of multiple categories!!
1) Movement Disorders 6) Neurodevelopmental Disorders
2) Dementias 7) Major Adult Psychiatric Disorders
3) Diseases of WM 8) Neurocutaneous Disorders
4) Neuromuscular Disorders 9) Cerebrovascular Diseases
5) Paroxysmal Disorders
1
,Movement disorders
- Cerebellar ataxias
- Parkinson disease (PD)
- Essential Tremor
- Inherited dystonias
- Huntington’s Disease (HD)
- Wilson Disease
- Primary familial brain calcifications
• Cerebellum is affected
• Hypokinetic disorders (slowness of movement) vs. Hyperkinetic disorders (excessive involuntary
movement
• Ataxia
o = umbrella term for a group of neurological conditions that gradually destroy your
cerebellum and affects your ability to control movement and send signals throughout
your nervous system
o Takes often a long term to be diagnosed
o Different types of ataxias (Friedreich’s, AOA2, gluten ataxia…)
o 2y-…y can be affected
o Genetic vs. acquired
o Progressive
Dementias
- Alzheimer Disease (AD)
- Frontotemporal Dementia (FTD)
- Dementia with Lewy Bodies (DLB)
- Prion Disease
• Signs of dementia
o Problems communicating
o Confusion of time and place
o Changes in mood or behavior
o Changes in personality
o Difficulty with simple tasks
o Problems with language
o Misplacing things
o Day-to-day forgetfulness
o Misplacing things
o Poor or decreased judgement
• Musical memory is preserved in patients with AD → SO not all regions are equally affected
2
,Diseases of White Matter
• Dysmyelinating= primary abnormality of myelin formation (Nieman Picks disease)
• Demyelinating = secondary destruction of normal myelin (MS)
- Adult onset heritable white matter disorders
- Alexander disease
- Pelizaeus Merzbacher disease
- Multiple sclerosis (demyelinating disease)
o Snowflake disease= it’s different for everyone
Neuromuscular Disorders
- Facioscapulohumeral muscular dystrophy (FSHD) = primary muscular disorders
- Duchenne muscular dystrophy (with genetic aspect)
- Congenital myopathies
- Spinal muscular atrophy (SMA)
- Amyotrophic lateral sclerosis (ALS)
- Spinal and bulbar muscular atrophy (SBMA)
- Hereditary spastic paraplegia (HSP)
- Neuropathy
• Affects upper and lower motor neurons and NMJ
• Often results in muscular diseases
• Cause: spinal cord doesn’t transmit signals anymore OR primary problem in muscles?
Paroxysmal disorders
- Epilepsy
- Migraine
- Periodic paralysis
- Episodic ataxias
- Disorders of sleep and circadian rhythm
• = disorders that occur unexpectedly
in episodes
(some may also fit in other categories)
3
, Neurodevelopmental disorders
- Autism spectrum disorder
- Cerebral palsy
- Tourette disorder and other tic disorders
- Sex chromosome aneuploidies
- Fragile X syndrome and fragile X associated tremor ataxia syndrome
Neurocutaneous disorders (phakomatoses)
- Neurofribromatosis type 1 (NF1)
- Tuberous sclerosis complex (TSC)
o Affects children
o They miss a gene that prevents tumors from growing in the body
- Von Hippel Lindau disease and sturge Weber syndrome
• Benign tumors in the brain that lead to for example epilepsy
Cerebrovascular Diseases
- Cerebrovascular autosomal-dominant arteriopathy with subcortical infarcts and
leukoencephalopathy (CADASIL)
Major Adults Psychiatric Disorders
- Addiction
- Obsessive compulsive disorder
- Bipolar disorder
Unifying themes in Neurological disorders
→ Often multiple disease subtypes
→ Multiple presentations of the disease even within a family
→ Challenging to obtain diagnoses
→ Progressive disease without a cure
→ Patients are extremely motivated to participate in research
1.2. GENETIC FACTORS
FACTORS SUGGESTING A NEUROGENETIC DISORDER
• A positive family history of the same/ similar neurological disorder
• A constellation of signs and symptoms suggesting a known genetic syndrome
• Subtle onset with chronic, progressive clinical course
• Consanguinity
• Increased frequency in a specific ethnic group
4
EXAM:
- Written + oral part
- Open questions
- Terms to explain
- Linking things
1. INTRODUCTION
➢ Broad classification of neurological diseases (with example)
➢ How to identify a (neuro)genetic disorder?
➢ Understanding of inheritance patterns and knowledge on key factors influencing them
➢ Concepts of gene identification: linkage versus genome-wide association studies
➢ Understanding of contribution of common and rare variants to neurological diseases
➢ Overview of types of disease-causing genetic variation (coding and non-coding mutations)
What are neurological disorders and how many people are affected by them?
1.1. CLASSIFICATION OF NEUROLOGICAL DISORDERS
• > 200 neurological disorders have been described
• Many classification systems exist e.g. based in clinical presentation, primary affected cell
type/ brain region temporal expression, …
o Some diseases are part of multiple categories!!
1) Movement Disorders 6) Neurodevelopmental Disorders
2) Dementias 7) Major Adult Psychiatric Disorders
3) Diseases of WM 8) Neurocutaneous Disorders
4) Neuromuscular Disorders 9) Cerebrovascular Diseases
5) Paroxysmal Disorders
1
,Movement disorders
- Cerebellar ataxias
- Parkinson disease (PD)
- Essential Tremor
- Inherited dystonias
- Huntington’s Disease (HD)
- Wilson Disease
- Primary familial brain calcifications
• Cerebellum is affected
• Hypokinetic disorders (slowness of movement) vs. Hyperkinetic disorders (excessive involuntary
movement
• Ataxia
o = umbrella term for a group of neurological conditions that gradually destroy your
cerebellum and affects your ability to control movement and send signals throughout
your nervous system
o Takes often a long term to be diagnosed
o Different types of ataxias (Friedreich’s, AOA2, gluten ataxia…)
o 2y-…y can be affected
o Genetic vs. acquired
o Progressive
Dementias
- Alzheimer Disease (AD)
- Frontotemporal Dementia (FTD)
- Dementia with Lewy Bodies (DLB)
- Prion Disease
• Signs of dementia
o Problems communicating
o Confusion of time and place
o Changes in mood or behavior
o Changes in personality
o Difficulty with simple tasks
o Problems with language
o Misplacing things
o Day-to-day forgetfulness
o Misplacing things
o Poor or decreased judgement
• Musical memory is preserved in patients with AD → SO not all regions are equally affected
2
,Diseases of White Matter
• Dysmyelinating= primary abnormality of myelin formation (Nieman Picks disease)
• Demyelinating = secondary destruction of normal myelin (MS)
- Adult onset heritable white matter disorders
- Alexander disease
- Pelizaeus Merzbacher disease
- Multiple sclerosis (demyelinating disease)
o Snowflake disease= it’s different for everyone
Neuromuscular Disorders
- Facioscapulohumeral muscular dystrophy (FSHD) = primary muscular disorders
- Duchenne muscular dystrophy (with genetic aspect)
- Congenital myopathies
- Spinal muscular atrophy (SMA)
- Amyotrophic lateral sclerosis (ALS)
- Spinal and bulbar muscular atrophy (SBMA)
- Hereditary spastic paraplegia (HSP)
- Neuropathy
• Affects upper and lower motor neurons and NMJ
• Often results in muscular diseases
• Cause: spinal cord doesn’t transmit signals anymore OR primary problem in muscles?
Paroxysmal disorders
- Epilepsy
- Migraine
- Periodic paralysis
- Episodic ataxias
- Disorders of sleep and circadian rhythm
• = disorders that occur unexpectedly
in episodes
(some may also fit in other categories)
3
, Neurodevelopmental disorders
- Autism spectrum disorder
- Cerebral palsy
- Tourette disorder and other tic disorders
- Sex chromosome aneuploidies
- Fragile X syndrome and fragile X associated tremor ataxia syndrome
Neurocutaneous disorders (phakomatoses)
- Neurofribromatosis type 1 (NF1)
- Tuberous sclerosis complex (TSC)
o Affects children
o They miss a gene that prevents tumors from growing in the body
- Von Hippel Lindau disease and sturge Weber syndrome
• Benign tumors in the brain that lead to for example epilepsy
Cerebrovascular Diseases
- Cerebrovascular autosomal-dominant arteriopathy with subcortical infarcts and
leukoencephalopathy (CADASIL)
Major Adults Psychiatric Disorders
- Addiction
- Obsessive compulsive disorder
- Bipolar disorder
Unifying themes in Neurological disorders
→ Often multiple disease subtypes
→ Multiple presentations of the disease even within a family
→ Challenging to obtain diagnoses
→ Progressive disease without a cure
→ Patients are extremely motivated to participate in research
1.2. GENETIC FACTORS
FACTORS SUGGESTING A NEUROGENETIC DISORDER
• A positive family history of the same/ similar neurological disorder
• A constellation of signs and symptoms suggesting a known genetic syndrome
• Subtle onset with chronic, progressive clinical course
• Consanguinity
• Increased frequency in a specific ethnic group
4
