brain diseases down syndrome (exam 1)

What genetic condition is the underlying cause of Down syndrome?

Trisomy of chromosome 21.

Who first described the clinical characteristics of Down syndrome in 1866?

Dr. John Langdon Down.

Why is Down syndrome medically classified as a 'syndrome'?

It involves a group of symptoms that regularly occur together, though individuals experience different combinations and degrees of severity.

What is the typical range of intellectual disability observed in individuals with Down syndrome?

Mild to moderate.

Down syndrome is often characterized by slowed or delayed development and a general reduction in the volume of _____.

Brain structures.

Individuals with Down syndrome have a significantly increased risk for the early onset of what neurodegenerative disease?

Alzheimer’s disease (or other dementia).

At what approximate age does the early onset of Alzheimer's disease typically manifest in Down syndrome patients?

40 years old.

What biological process failure results in an extra copy of a chromosome (2n+1)?

Defects in chromosomal segregation.

The presence of an abnormal number of chromosomes, such as 45 or 47, is known as _____.

Aneuploidy.

During which type of cell division does the chromosomal abnormality leading to Down syndrome usually occur?

Meiosis.

What is 'nondisjunction' in the context of cell division?

The process in which sister chromatids fail to completely separate, resulting in a daughter cell with extra genomic information.

Which type of trisomy 21 occurs when the egg or sperm contains the extra copy and all resulting cells have it?

Complete trisomy.

What percentage of Down syndrome cases are caused by complete trisomy?

95%.

What is 'mosaic trisomy' in Down syndrome?

A condition where some cells in the body have an extra copy of chromosome 21, but others do not.

Which form of trisomy occurs when an extra portion of chromosome 21 attaches to its sister chromosome?

Translocation trisomy.

Trisomies of chromosomes 1 through 12 generally result in what clinical outcome?

Very early miscarriage occurring before evaluation is possible.

Which specific trisomy condition is known as Edwards syndrome?

Trisomy 18.

What is the common name for the condition caused by Trisomy 13?

Patau syndrome.

Which trisomy is the most frequently occurring among live births in the United States?

Trisomy 21 (Down syndrome).

What is the approximate incidence rate of Down syndrome per live births in the U.S.?

1 in 700.

Down syndrome is considered the most common genetic cause of _____.

Intellectual disability.

What is the primary risk factor associated with an increased likelihood of giving birth to a child with Down syndrome?

Increasing maternal age.

Why are the majority of babies with Down syndrome born to mothers under 35 years old despite lower individual risk?

There is a much higher total number of births among women in the younger age group.

The majority of Down syndrome cases result from nondisjunction during which specific stage of meiosis?

Maternal Meiosis I.

What is the primary limitation of prenatal screening tests for Down syndrome?

They are not sufficient for a definitive diagnosis.

What markers are analyzed in a mother's blood during prenatal screening for Down syndrome?

Specific proteins that suggest an increased risk.

What can an ultrasound detect at the back of a fetus's neck that may indicate Down syndrome?

Excess fluid.

What is the main advantage of prenatal diagnostic testing over screening?

It is sufficient for a definitive diagnosis.

From which three sources can samples for prenatal diagnostic testing be obtained?

Amniotic fluid, placenta, or umbilical cord blood.

What is the standard diagnostic technique used to visualize and count chromosomes (G-Banded)?

Karyotype.

Which diagnostic method uses fluorescently labeled DNA probes to target genes on chromosome 21?

Fluorescence in situ hybridization (FISH).

How does Quantitative PCR (qPCR) detect trisomy 21?

By identifying three different allele sizes for genes on chromosome 21.

What does Paralogous Sequence Quantification (PSQ) compare to detect chromosome 21 abnormalities?

Differences in sequence percentages between chromosome 5 and chromosome 21.

What is the central hypothesis regarding the molecular cause of developmental problems in Down syndrome?

Overexpression of genes present on the extra copy of chromosome 21.

What is the approximate size of human chromosome 21 (HSA21) in Megabases?

∼48 Mb.

Approximately how many protein-coding genes are located on chromosome 21?

235.

What is the name of the 5.4 Mb region on HSA21q22 once thought to cause most Down syndrome symptoms?

Down syndrome critical region (DSCR).

In theory, by what percentage should gene expression increase on chromosome 21 due to trisomy?

50% (a 3:2 ratio).

According to human studies, what percentage of genes on HSA21 are actually expressed at the expected 1.5× level?

22%.

How can upregulated genes on HSA21 influence the expression of genes on other chromosomes?

By overexpressing transcription factors that target genes on different chromosomes.

The 'Phenotypic Threshold Effect' suggests that genetic defects manifest only when _____.

A threshold level of gene expression is exceeded.

Which HSA21 gene encodes a tyrosine kinase that regulates neuronal differentiation and precursor cell division?

DYRK1A.

How does overexpression of DYRK1A contribute to reduced brain volume in Down syndrome?

It causes neural precursor cells to stop dividing and differentiate prematurely, leading to fewer total neurons.

Which protein located on chromosome 21 is directly linked to the development of senile plaques in Alzheimer's disease?

Amyloid Precursor Protein (APP).

What is the pathogenic role of the HSA21 gene SOD1?

It decreases hippocampal neuronal progenitors and increases sensitivity to apoptosis.

Which gene on HSA21 is a nerve terminal protein that, when overexpressed, leads to enlarged early endosomes?

Synaptojanin 1 (SYNJ1).

How does RCAN1 overexpression contribute to the pathology of Down syndrome?

It inhibits calcineurin-dependent signaling and increases tau phosphorylation via GSK3$\beta$.

What role do enhancers, silencers, and promoters play in the severity of Down syndrome phenotypes?

They contribute to allele-specific levels of gene expression, which can influence symptom severity.

What legislative change occurred in 2010 with the signing of Rosa’s Law?

The removal of the word 'retardation' from federal legislation.

What was the average life expectancy for a person with Down syndrome in 1946 vs. 2021?

12 years in 1946 vs. 60 years in 2021.

What is the primary purpose of Occupational Therapy for individuals with Down syndrome?

To assist with difficulties encountered in the workplace.

What type of therapy is used to address skeletal-muscular difficulties in Down syndrome?

Physical therapy.

Which HSA21 gene is an E3 ubiquitin ligase that targets AKT kinase and increases neuronal apoptosis?

TTC3.

How does the gene KCNJ6 (GIRK2) contribute to the Down syndrome phenotype?

It causes a GABAergic excitatory-inhibitory imbalance by modulating potassium channel current.

What is the proposed direct effect of APP overexpression in Down syndrome brains?

Increased accumulation of Alzheimer-like senile plaque pathology.

Why is the diagnosis of comorbid conditions sometimes delayed in individuals with Down syndrome?

Diagnostic overshadowing and communication difficulties.

Which HSA21 protein acts as a cell adhesion molecule and can inhibit dendritic branching when overexpressed?

DSCAM.

In terms of gross motor milestones, what is the typical range for a child with Down syndrome to start walking alone?

1 to 4 years.

According to the gene expression hypothesis, why might expression levels be lower than 1.5× despite an extra chromosome?

Feedback mechanisms or epigenetic modifications (like DNA methylation) may limit gene regulation.