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Understanding The Difference Between Down Syndrome And Autism
Down syndrome and autism spectrum disorder can both involve a need for additional support. However, these are distinct diagnoses with different underlying causes and presentations.
Down syndrome (DS) and autism spectrum disorder (ASD) are both developmental disorders, conditions present from childhood that affect typical growth and development.
While DS and ASD may both require additional support and can share symptoms related to developmental delay, important differences set them apart.
Although they both fall under the broad category of developmental disorders, DS and ASD are separate conditions.
DS is a genetic disorder, while ASD is a neurodevelopmental disorder. Their specific classifications indicate their primary difference — underlying cause.
Underlying causes
DS is caused by the presence of an extra (full or partial) copy of chromosome 21. Rather than 46 chromosomes total, 23 from each parent, children with DS have 47 chromosomes.
Because chromosome 21 contains genes that influence aspects of whole-body development, having an extra copy leads to a specific set of symptoms that differentiate DS from other developmental conditions.
The causes of ASD are not as well understood and can't yet be traced to a single underlying factor. As a neurodevelopmental disorder, alterations in brain function and structure are responsible for ASD symptoms. But it isn't clear why these changes occur.
A complex dynamic of genetic predispositions and environmental factors is thought to influence the development of ASD.
Symptom variety
The different causes of DS and ASD result in unique symptom presentations, even though both conditions can involve general developmental challenges.
In DS, chromosome 21's role in development affects more than just the brain. For example, chromosome 21 contains genes related to muscle tone and growth that influence physical appearance.
This is why DS is associated with common physical traits. Children living with DS may also experience physical challenges related to atypical organ development or immune and metabolic dysfunction.
ASD, on the other hand, stems from altered brain function that impacts the way you perceive and interact with the world around you. Its symptoms primarily involve cognitive and behavioral challenges.
While ASD can feature physical symptoms like challenges with coordination or digestive complaints, these are considered secondary effects of altered brain function.
Simply put, DS can affect the development of multiple systems in the body, including the brain, while ASD is only associated with altered brain development.
DS can be tested for at birth with genetic screening, regardless of symptoms. ASD can be diagnosed as early as 15 months old.
ASD, however, is typically recognized as children get older, and symptoms are seen through persistent behavioral patterns.
DS features physical, cognitive, and developmental symptoms. These can vary in presentation but often include:
Cognitive and developmental symptoms
Physical symptoms
People living with DS are also more likely than the general public to be born with heart abnormalities or to experience hearing or vision problems.
ASD symptoms are seen across areas of communication, social interaction, and restrictive/repetitive behavior. ASD is referred to as a spectrum disorder because symptoms vary significantly in both presentation and severity.
Communication and social symptoms
Restrictive and repetitive behavior symptoms
Intellectual disability, or limitations in high-level thought processes like abstract thinking and reasoning, is possible in ASD but does not affect everyone with ASD.
Being diagnosed with DS is considered a risk factor for ASD. But this does not mean living with DS causes ASD or that everyone born with Down syndrome will eventually be diagnosed with ASD.
The increased risk may come from shared genetic pathways that predispose you to ASD if you were born with DS.
Signs of autism in Down syndrome
You can be diagnosed with both ASD and DS. When two distinct conditions occur together like this, it's known as "comorbidity."
Diagnosing ASD comorbid with DS can be challenging due to overlapping symptoms and the varied presentations of ASD.
During a comprehensive evaluation for comorbidity, your child's developmental specialist will look for communication, social, and behavioral signs that are more aligned with ASD.
They will also assess signs that typically become more pronounced when ASD and DS occur together, such as:
Both ASD and DS involve individualized care that takes into consideration your specific symptoms and experiences. Under either diagnosis, finding the right level of emotional and functional support is the ultimate goal.
ASD and DS interventions help children develop new skills related to social interactions, communication, and adaptive functioning. They can include:
Children living with DS may also need regular medical check-ups to manage other health conditions related to DS, like heart abnormalities or visual impairment.
While there are no medications that treat DS or ASD directly, medications may be used to help manage secondary psychological or physical symptoms.
DS and ASD are distinct diagnoses. They often share overlapping developmental delays but are differentiated by causes and symptom variety.
As a genetic disorder, DS can affect the development of multiple systems in the body. Its symptoms are physical, cognitive, and developmental.
ASD, as a neurodevelopmental disorder, is caused by altered brain function that results in cognitive and behavioral symptoms. However, secondary physical challenges are possible.
While there's no cure for ASD or DS, the right emotional and functional support can help children successfully build skills for everyday life.
Brain Cell Types Are Affected Differently By Rett Syndrome Mutation, Researchers Discover
Rett syndrome is a X-chromosome-linked neurodevelopmental disorder; it can lead to loss of coordination, mobility, ability to speak, and use of the hands, among other symptoms. The syndrome is typically caused by mutations within the gene MECP2.
Researchers in Whitehead Institute Founding Member Rudolf Jaenisch's lab have studied Rett syndrome for many years in order to understand the biological mechanisms that cause disease symptoms, and to identify possible avenues for treatments or a cure.
Jaenisch and colleagues have gained many insights into the biology of Rett syndrome and developed tools that can rescue neurons from Rett syndrome symptoms in lab models. However, much about the biology of Rett syndrome remains unknown.
New research from Jaenisch and postdoc Danielle Tomasello focuses on an understudied question: how Rett syndrome affects cell types in the human brain other than neurons. Specifically, Tomasello investigated the effects of Rett syndrome on astrocytes, a type of brain cell that supports and provides energy for neurons.
The work, published in Scientific Reports, details changes that occur in Rett syndrome astrocytes, in particular in relation to their mitochondria, and shows how these changes directly impact neurons. The findings provide a new framework for thinking about Rett syndrome and possible new avenues for therapies.
"By considering Rett syndrome from a different perspective, this project expands our understanding of a multifaceted and thus far incurable disease," says Jaenisch, who is also a professor of biology at the Massachusetts Institute of Technology.
Mitochondria are organelles that generate energy, which cells use to carry out their functions, and mitochondrial dysfunction was known to occur in Rett syndrome. Jaenisch and Tomasello found that mitochondria in astrocytes are particularly affected, even more so than mitochondria in neurons.
Tomasello grew human stem-cell-derived astrocytes in 2D cultures and also grew 3D organoids: mini brain-like tissues that contain multiple cell types growing in a structure that resembles actual brain anatomy. This approach allowed Tomasello to use human cells, rather than an animal model, and to study how cells behave within a brain-like environment.
When the researchers observed Rett astrocytes grown in these conditions, they found that the mitochondria were misshapen. They were short, small circles instead of large, long ovals. Additional studies showed evidence of the mitochondria experiencing stress and not being able to generate enough energy through their usual processes.
Because the mitochondria did not have enough of the typical proteins they use to make energy, they began to break down the cell's supply of the building blocks of proteins, amino acids, for parts to make up for the missing material. Additionally, the researchers observed an increase in reactive oxygen species, byproducts of mitochondrial metabolism that are toxic to the cell.
Further experiments suggested that the cells try to compensate for this mitochondrial stress by increasing transcription of mitochondrial genes. For example, Tomasello found that regions of DNA called promoters that can increase expression of key mitochondrial genes were more open for the cell to use in Rett astrocytes. Together, these findings paint a picture of severe mitochondrial dysfunction in Rett astrocytes.
Although mitochondria in Rett neurons did not have such severe defects, astrocytes and neurons have a close relationship. Not only do neurons rely on astrocytes to supply them with energy, they even accept mitochondria from astrocytes to use for themselves.
Jaenisch and Tomasello found that neurons take up dysfunctional mitochondria from Rett astrocytes at a higher rate than they take up mitochondria from unaffected astrocytes. This means that the effects of Rett syndrome on astrocytes have a direct effect on neurons: the dysfunctional mitochondria from the astrocytes end up in the neurons, where they cause damage.
Tomasello took mitochondria from Rett astrocytes and placed them on both healthy and Rett neurons. In either case, the neurons took up the dysfunctional mitochondria in large numbers and then experienced significant problems.
The neurons entered a hyperexcitable state that is ultimately toxic to the brain. The neurons also contained higher levels of reactive oxygen species, the toxic byproducts of mitochondrial metabolism, which can cause widespread damage. These effects occurred even in otherwise healthy neurons that did not themselves contain a Rett-causing MECP2 mutation.
"This shows that in order to understand Rett syndrome, we need to look beyond what's happening in neurons to other cell types," Tomasello says.
Learning about the role that astrocytes play in Rett syndrome could provide new avenues for therapies. The researchers found that supplying affected astrocytes with healthy mitochondria helped them to recover normal mitochondrial function.
This suggests to Tomasello that one possibility for future Rett syndrome therapies could be something that either targets mitochondria, or supplies additional mitochondria through the bloodstream.
Together, these insights and their possible medical implications demonstrate the importance of taking a broader look at the foundational biology underlying a disease.
More information: Danielle L. Tomasello et al, Mitochondrial dysfunction and increased reactive oxygen species production in MECP2 mutant astrocytes and their impact on neurons, Scientific Reports (2024). DOI: 10.1038/s41598-024-71040-y
Citation: Brain cell types are affected differently by Rett syndrome mutation, researchers discover (2024, September 9) retrieved 15 September 2024 from https://medicalxpress.Com/news/2024-09-brain-cell-affected-differently-rett.Html
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How Do Genetic Mutations Cause Disease?
Key types of mutationsMutation patterns and diseasesGenetic testing and treatmentsReferencesFurther reading
Nucleic acids are building blocks of DNA or RNA of any cellular organisms or viruses.1, 2,3 A mutation is a change in the nucleotide sequence of a gene, which may occur due to errors in DNA replication during cell division, viral infection, and exposure to mutagens.4
Image Credit: Natali _ Mis/Shutterstock.Com
Mutagens (e.G., chemicals and radiation) react with DNA and can alter the structures of individual nucleotides. An impaired DNA repair system that is responsible for correcting any errors during cell division is directly associated with gene mutation.5
Key types of mutationsGenetic disorders can occur due to mutations in one gene (monogenic), multiple genes (multifactorial inheritance), and mutation in one or more chromosomes. Point mutations are where one nucleotide in a genomic sequence is replaced or substituted with another.6 Chromosomes can fuse, translocate, and break, resulting in the loss of a large number of functional genes, whose consequences can be harmful.7
Different types of transposable elements are regarded as another source of mutation. These are small DNA entities that can move around within the entire genome. A transposon might disrupt existing gene functions when it gets inserted in the middle of another genetic region, trigger dormant gene functions, or produce new proteins by inserting different genetic materials into an existing genetic sequence.8
Genetic mutation may also occur through the insertion or deletion of a few nucleotides.6 In the case of nonsynonymous mutation, an entire amino acid sequence is changed. This type of mutation results in the production of a different protein or premature termination of a protein. Synonymous mutations are linked with changes in amino acids that are encoded by multiple codons.9
Mutation patterns and diseasesCell divisions are of two types: mitosis and meiosis. Mitosis occurs in somatic cells, whereas meiosis occurs in the gamete cells, i.E., egg and sperm cells. Mutations appearing in reproductive cells, called germline mutation, are heritable as they are passed on to offspring. This type of mutation is also known as an inherited mutation. Somatic mutations that occur in cells other than germ cells are not heritable.
Acquired mutations occur after a person is born due to "wear and tear" of genes over time. As stated above, this type of mutation occurs due to aging, exposure to toxins and chemicals, and certain viral infections.10
From an evolutionary perspective, somatic mutations have no significant impact, but they may lead to disease conditions if they are systematic and alter the cell survival capacity. For instance, cancers are potent somatic mutations that influence an organism's survival.
Many genetic disorders, such as cystic fibrosis, Down syndrome, and sickle cell disease, are inherited. Different genetic mutation patterns that are passed on from the parent to a child and lead to disease conditions are discussed below:11
Image Credit: Katrien Francois/Shutterstock.Com
Genetic testing and treatmentsGenetic tests, such as cytogenetic, biochemical, and molecular tests, are performed for newborn screening, carrier testing, prenatal diagnosis, and disease diagnostics.12 In many countries, such as the USA, every newborn is screened for several genetic diseases. Early disease detection improves outcome rates.
Carrier testing helps a couple to understand if they are carriers of a recessive allele for genetic diseases, such as sickle cell anemia, cystic fibrosis, and Tay-Sachs disease. In prenatal diagnostic testing, a fetus's genes or chromosomes are tested to identify the presence of specific mutations. Genetic tests are also used to confirm a diagnosis in symptomatic individuals and monitor disease prognosis.
Genetic counseling helps patients and their families to understand the implications of genetic testing and treatment strategies. At present, many advanced gene therapies are available that entail the correction or replacement of faulty genes with healthy ones to cure or prevent genetic disorders, such as hemophilia and cystic fibrosis.13
References
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