H1: INTRODUCTION TO NEUROGENETICS
1.1 INTRODUCTION
1.1.1 NEUROLOGICAL DISORDERS
Neurological disorder
= Diseases of the central and peripheral nervous system:
● The brain and spinal cord
● Cranial nerves + peripheral nerves + nerve roots
● Autonomic nervous system
● Neuromuscular junction and muscles
These disorders include:
1. Epilepsy
2. Alzheimer disease and other dementias
3. Cerebrovascular diseases including stroke
4. Migraine and other headache disorders
5. Multiple sclerosis
6. Parkinson’s disease
7. Neuroinfections
8. Brain tumours
9. Traumatic disorders of the nervous system due to head trauma
10. Neurological disorders as a result of malnutrition
1.2 CLASSIFICATION OF NEUROLOGICAL DISORDERS
1.2.1 OVERVIEW
Classification
Many classification systems exist, based on :
● Clinical presentation
● Primary affected cell type or brain region
● Temporal expression
The classification we will use :
1. Movement disorders 6. Neurodevelopmental disorders
2. Dementias 7. Major Adult Psychiatric Disorders
3. Diseases of White Matter 8. Neurocutaneous Disorders
4. Neuromuscular Disorders 9. Cerebrovascular Diseases
5. Paroxysmal Disorders
1
,1.2.2 MOVEMENT DISORDERS
Movement disorders
Cerebellum is defected → affects your ability to control movements.
Movement affected by 2 ways
● Hypokinetic disorders → too slow movements
● Hyperkinetic disorders → excessive involuntary movements
Overview
1. Cerebellar ataxias
2. Parkinson Disease (PD)
3. Essential Tremor
4. Inherited dystonias
5. Huntington's Disease (HD)
6. Wilson Disease
7. Primary familial brain calcifications
1.2.3 DEMENTIAS
Dementias → not all parts of the brain are equally affected
Overview
1. Alzheimer disease (AD)
2. Frontotemporal dementia (FTD)
3. Dementia with Lewy bodies (DLB)
4. Prion disease
1.2.4 DISEASES OF WHITE MATTER
Diseases of white matter
White matter in the brains is affected → resulting in white matter lesions = can happen primarily or secondary:
● Dysmyelinating = primary abnormality of myelin formation → myelin not correctly formed
● Demyelinating = secondary destruction of normal myelin → myelin was formed normal but
afterwards destructed
Overview
1. Adult onset heritable white matter disorders
2. Alexander disease
3. Pelizaeus Merzbacher disease
4. Multiple sclerosis ( = demyelinating disease)
2
,1.2.5 NEUROMUSCULAR DISORDERS
Neuromuscular disorders
= a broad group of conditions that affect the nerves that control voluntary muscles and the muscles themselves
= caused by affected:
● Motor neurons (lower or upper)
● Neuromuscular junction
Overview
1. Facioscapulohumeral muscular dystrophy (FSHD)
2. Congenital myopathies
3. Spinal muscular atrophy (SMA)
4. Amyotrophic lateral sclerosis (ALS)
5. Spinal and bulbar muscular atrophy (SBMA)
6. Hereditary spastic paraplegia (HSP)
7. Neuropathy
8. Duchenne muscular dystrophy
1.2.6 PAROXYSMAL DISORDERS
Paroxysmal disorders
= Disorders that occur unexpectedly in episodes
Overview
1. Epilepsy
2. Migraine
3. Periodic paralysis
4. Episodic ataxias
5. Disorders of sleep and circadian rhythms
1.2.7 NEURODEVELOPMENTAL DISORDERS
Neurodevelopmental disorders
= Arise from abnormal brain development or function
Overview
1. Autism spectrum disorder
2. Cerebral palsy
3. Tourette disorder and other tic disorders
4. Sex chromosome aneuploidies
5. Fragile X syndrome and fragile X associated tremor ataxia syndrome
3
, 1.2.8 NEUROCUTANEOUS DISORDERS
Neurocutaneous disorders (phakomatoses)
= Characterized by abnormal development of cells in the skin, brain and spinal cord.
= They often result in non-malignant tumors or lesions, spread over whole body
= The patients will not die due to the tumors but struggle with disabilities, mental retardation,...
Overview
1. Neurofibromatosis type 1 (NF1)
2. Tuberous sclerosis complex (TSC)
3. Von Hippel Lindau disease and Sturge Weber syndrome
1.2.9 CEREBROVASCULAR DISEASES
Cerebrovascular diseases
= In these diseases the blood vessels in the brain will be affected causing neurological disorders
Example
= Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)
1.2.10 MAJOR ADULT PSYCHIATRIC DISORDERS
Major adult psychiatric disorders
● Addiction
● Obsessive compulsive disorder
● Bipolar disorder
1.2.11 IN CONCLUSION
Unifying themes ins neurological disorders
● Often multiple disease subtypes
● Multiple presentations of the disease even within a family
● Challenging to obtain diagnoses → takes long
● Progressive disease without a cure
● Patients are extremely motivated to participate in research
4
1.1 INTRODUCTION
1.1.1 NEUROLOGICAL DISORDERS
Neurological disorder
= Diseases of the central and peripheral nervous system:
● The brain and spinal cord
● Cranial nerves + peripheral nerves + nerve roots
● Autonomic nervous system
● Neuromuscular junction and muscles
These disorders include:
1. Epilepsy
2. Alzheimer disease and other dementias
3. Cerebrovascular diseases including stroke
4. Migraine and other headache disorders
5. Multiple sclerosis
6. Parkinson’s disease
7. Neuroinfections
8. Brain tumours
9. Traumatic disorders of the nervous system due to head trauma
10. Neurological disorders as a result of malnutrition
1.2 CLASSIFICATION OF NEUROLOGICAL DISORDERS
1.2.1 OVERVIEW
Classification
Many classification systems exist, based on :
● Clinical presentation
● Primary affected cell type or brain region
● Temporal expression
The classification we will use :
1. Movement disorders 6. Neurodevelopmental disorders
2. Dementias 7. Major Adult Psychiatric Disorders
3. Diseases of White Matter 8. Neurocutaneous Disorders
4. Neuromuscular Disorders 9. Cerebrovascular Diseases
5. Paroxysmal Disorders
1
,1.2.2 MOVEMENT DISORDERS
Movement disorders
Cerebellum is defected → affects your ability to control movements.
Movement affected by 2 ways
● Hypokinetic disorders → too slow movements
● Hyperkinetic disorders → excessive involuntary movements
Overview
1. Cerebellar ataxias
2. Parkinson Disease (PD)
3. Essential Tremor
4. Inherited dystonias
5. Huntington's Disease (HD)
6. Wilson Disease
7. Primary familial brain calcifications
1.2.3 DEMENTIAS
Dementias → not all parts of the brain are equally affected
Overview
1. Alzheimer disease (AD)
2. Frontotemporal dementia (FTD)
3. Dementia with Lewy bodies (DLB)
4. Prion disease
1.2.4 DISEASES OF WHITE MATTER
Diseases of white matter
White matter in the brains is affected → resulting in white matter lesions = can happen primarily or secondary:
● Dysmyelinating = primary abnormality of myelin formation → myelin not correctly formed
● Demyelinating = secondary destruction of normal myelin → myelin was formed normal but
afterwards destructed
Overview
1. Adult onset heritable white matter disorders
2. Alexander disease
3. Pelizaeus Merzbacher disease
4. Multiple sclerosis ( = demyelinating disease)
2
,1.2.5 NEUROMUSCULAR DISORDERS
Neuromuscular disorders
= a broad group of conditions that affect the nerves that control voluntary muscles and the muscles themselves
= caused by affected:
● Motor neurons (lower or upper)
● Neuromuscular junction
Overview
1. Facioscapulohumeral muscular dystrophy (FSHD)
2. Congenital myopathies
3. Spinal muscular atrophy (SMA)
4. Amyotrophic lateral sclerosis (ALS)
5. Spinal and bulbar muscular atrophy (SBMA)
6. Hereditary spastic paraplegia (HSP)
7. Neuropathy
8. Duchenne muscular dystrophy
1.2.6 PAROXYSMAL DISORDERS
Paroxysmal disorders
= Disorders that occur unexpectedly in episodes
Overview
1. Epilepsy
2. Migraine
3. Periodic paralysis
4. Episodic ataxias
5. Disorders of sleep and circadian rhythms
1.2.7 NEURODEVELOPMENTAL DISORDERS
Neurodevelopmental disorders
= Arise from abnormal brain development or function
Overview
1. Autism spectrum disorder
2. Cerebral palsy
3. Tourette disorder and other tic disorders
4. Sex chromosome aneuploidies
5. Fragile X syndrome and fragile X associated tremor ataxia syndrome
3
, 1.2.8 NEUROCUTANEOUS DISORDERS
Neurocutaneous disorders (phakomatoses)
= Characterized by abnormal development of cells in the skin, brain and spinal cord.
= They often result in non-malignant tumors or lesions, spread over whole body
= The patients will not die due to the tumors but struggle with disabilities, mental retardation,...
Overview
1. Neurofibromatosis type 1 (NF1)
2. Tuberous sclerosis complex (TSC)
3. Von Hippel Lindau disease and Sturge Weber syndrome
1.2.9 CEREBROVASCULAR DISEASES
Cerebrovascular diseases
= In these diseases the blood vessels in the brain will be affected causing neurological disorders
Example
= Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)
1.2.10 MAJOR ADULT PSYCHIATRIC DISORDERS
Major adult psychiatric disorders
● Addiction
● Obsessive compulsive disorder
● Bipolar disorder
1.2.11 IN CONCLUSION
Unifying themes ins neurological disorders
● Often multiple disease subtypes
● Multiple presentations of the disease even within a family
● Challenging to obtain diagnoses → takes long
● Progressive disease without a cure
● Patients are extremely motivated to participate in research
4
