Introduction to neurogenetics
Confidence Confident
Moment of lecture @February 28, 2024
Review @March 17, 2024
Materials Class 1 - Introduction to Neurogenetics.pdf
Last Edited @March 12, 2025 10:01 AM
Neurological disorders are a major health problem and contains many diseases.
Genetic studies are very important because they give a first indication about
what is wrong in these diseases. You can classify them in many different ways
for example: a classification system based on clinical presentation, based on
primary affected cell type or brain region or based on temporal expression. The
classification system used in this course is ???
Classification of neurological disorders
Movement Disorders
Dementias
Diseases of White Matter
Neuromuscular Disorders
Paroxysmal Disorders
Neurodevelopmental Disorders
Major Adult Psychiatric Disorders
Neurocutaneous Disorders
Cerebrovascular Diseases
Movement disorders
The most known one is Parkinson Disease. They are all caused by a defect in
the cerebellum. You can have:
Hyperkinetic: faster movement
Hypokinetic: slower movement
Introduction to neurogenetics 1
, Video about Ataxia: diversity within the disease, there are genetic and non-
genetic factors, many different forms, etc.
Dementias
Examples are Alzheimer disease (AD), Frontotemporal dementia (FTD),
Dementia with Lewy bodies (DLB) and Prion disease.
Disease of the white matter
Example: Multiple Sclerose
Dysmyelinating = primary abnormality of myelin formation
Here you can have that the myeline is first normally formed and secondary
destructed or you can have dysmyelinating diseases where the primary
abnormality is in the formation of the myelin:
Demyelinating = secondary destruction of normal myelin
The diagnosis can take a long time because people are not always taken
seriously.
Neuromuscular Disorders
This is a large group of disease that affect the lower and upper motorneurons
and also the neuromuscular junction. For this category it is often difficult to
make a distinction between neuromuscular and muscular diseases.
Example: Spinal muscular atrophy(SMA)
Introduction to neurogenetics 2
, Paroxysmal disorders
= disorders that occur unexpectedly in episodes. Example: epilepsy, migraine,
etc.
Neurodevelopmental Disorders
This are not always adults but can also be present in childeren. Example: fragile
X syndrome or autism spectrum disorder.
Neurocutaneous disorders (phakomatoses)
This are like tumors in the brain, the people don’t die from it but they have
disabilities. Most well-known is neurofibromatosis type 1 (NF1) but Tuberous
sclerosis complex is also well-known.
Cerebrovascular Diseases
The genetic well-known form is CADASIL. There are 650K bloodvessels in the
brain.
Major Adult Psychiatric Disorders
This are things like bipolar disorder, etc.
⇒ In neurological disorders there often are multiple subtypes, even within 1
family. This also means that it is a challenge to diagnose people or find the
exact genetic background of the disease. Most of these diseases are
progressive without a cure and most of the patients are extremely motivated to
participate in research.
The neurogenetic part of the disorders
Most of the diseases are caused by a genetic defect. Knowing if a disease is
genetic you look at:
Introduction to neurogenetics 3
, Family history
Neurologists use their knowledge (combinations of signs and symptoms)
Subtle onset with chronic, progressive clinical course
Consanguinity (parents are related to each other)
Increased frequency in a specific ethnic group because the genetic
composition of the genome is different between different groups
Although it could be that there are multiple people in a family with the same
disease but it is not genetic, this could be due to:
Environmental factors
It is a common late-onset condition
It is a sporadic case
It is important to also look at reasons for:
Genetic but not in the family: recessive genes (it may not look genetic but it
actually is), de novo mutations, sometimes multiple genes have to come
together to have the disease (= oligogenic, not monogenic), sometimes
there is early death within the family (it may not look genetic but it actually
is), sometimes people have different diseases (it has different
representations) or non-paternity (the father is not the biological father).
Even in families with monogenic disease, inheritance pattern may be
unclear:
Incomplete family information
Early death to other causes in family members who transmitted the
gene defect
Non-paternity
Broad spectrum in clinical presentations
Reduced penetrance: some individuals who carry the disease gene
may stay unaffected
In the family but not genetic: this can be due to environmental factors, it are
common diseases.
⇒ Genetics plays an important role.
Inheritance patterns
Introduction to neurogenetics 4
Confidence Confident
Moment of lecture @February 28, 2024
Review @March 17, 2024
Materials Class 1 - Introduction to Neurogenetics.pdf
Last Edited @March 12, 2025 10:01 AM
Neurological disorders are a major health problem and contains many diseases.
Genetic studies are very important because they give a first indication about
what is wrong in these diseases. You can classify them in many different ways
for example: a classification system based on clinical presentation, based on
primary affected cell type or brain region or based on temporal expression. The
classification system used in this course is ???
Classification of neurological disorders
Movement Disorders
Dementias
Diseases of White Matter
Neuromuscular Disorders
Paroxysmal Disorders
Neurodevelopmental Disorders
Major Adult Psychiatric Disorders
Neurocutaneous Disorders
Cerebrovascular Diseases
Movement disorders
The most known one is Parkinson Disease. They are all caused by a defect in
the cerebellum. You can have:
Hyperkinetic: faster movement
Hypokinetic: slower movement
Introduction to neurogenetics 1
, Video about Ataxia: diversity within the disease, there are genetic and non-
genetic factors, many different forms, etc.
Dementias
Examples are Alzheimer disease (AD), Frontotemporal dementia (FTD),
Dementia with Lewy bodies (DLB) and Prion disease.
Disease of the white matter
Example: Multiple Sclerose
Dysmyelinating = primary abnormality of myelin formation
Here you can have that the myeline is first normally formed and secondary
destructed or you can have dysmyelinating diseases where the primary
abnormality is in the formation of the myelin:
Demyelinating = secondary destruction of normal myelin
The diagnosis can take a long time because people are not always taken
seriously.
Neuromuscular Disorders
This is a large group of disease that affect the lower and upper motorneurons
and also the neuromuscular junction. For this category it is often difficult to
make a distinction between neuromuscular and muscular diseases.
Example: Spinal muscular atrophy(SMA)
Introduction to neurogenetics 2
, Paroxysmal disorders
= disorders that occur unexpectedly in episodes. Example: epilepsy, migraine,
etc.
Neurodevelopmental Disorders
This are not always adults but can also be present in childeren. Example: fragile
X syndrome or autism spectrum disorder.
Neurocutaneous disorders (phakomatoses)
This are like tumors in the brain, the people don’t die from it but they have
disabilities. Most well-known is neurofibromatosis type 1 (NF1) but Tuberous
sclerosis complex is also well-known.
Cerebrovascular Diseases
The genetic well-known form is CADASIL. There are 650K bloodvessels in the
brain.
Major Adult Psychiatric Disorders
This are things like bipolar disorder, etc.
⇒ In neurological disorders there often are multiple subtypes, even within 1
family. This also means that it is a challenge to diagnose people or find the
exact genetic background of the disease. Most of these diseases are
progressive without a cure and most of the patients are extremely motivated to
participate in research.
The neurogenetic part of the disorders
Most of the diseases are caused by a genetic defect. Knowing if a disease is
genetic you look at:
Introduction to neurogenetics 3
, Family history
Neurologists use their knowledge (combinations of signs and symptoms)
Subtle onset with chronic, progressive clinical course
Consanguinity (parents are related to each other)
Increased frequency in a specific ethnic group because the genetic
composition of the genome is different between different groups
Although it could be that there are multiple people in a family with the same
disease but it is not genetic, this could be due to:
Environmental factors
It is a common late-onset condition
It is a sporadic case
It is important to also look at reasons for:
Genetic but not in the family: recessive genes (it may not look genetic but it
actually is), de novo mutations, sometimes multiple genes have to come
together to have the disease (= oligogenic, not monogenic), sometimes
there is early death within the family (it may not look genetic but it actually
is), sometimes people have different diseases (it has different
representations) or non-paternity (the father is not the biological father).
Even in families with monogenic disease, inheritance pattern may be
unclear:
Incomplete family information
Early death to other causes in family members who transmitted the
gene defect
Non-paternity
Broad spectrum in clinical presentations
Reduced penetrance: some individuals who carry the disease gene
may stay unaffected
In the family but not genetic: this can be due to environmental factors, it are
common diseases.
⇒ Genetics plays an important role.
Inheritance patterns
Introduction to neurogenetics 4
