Down Syndrome (DS) Overview

Flashcards covering key concepts related to Down Syndrome, its causes, clinical descriptions, diagnosis, genetics, and therapeutic approaches.

Down Syndrome (DS)

A genetic condition caused by trisomy of chromosome 21, leading to physical symptoms and intellectual disabilities.

Epidemiology of DS

The occurrence of Down Syndrome is approximately 1:650 to 1:1,000 live births, with maternal age affecting the frequency.

Trisomy 21

A genetic disorder caused by an extra copy of chromosome 21, which is responsible for Down Syndrome.

Hypotonia

Decreased muscle tone often seen in individuals with Down Syndrome.

Karyotyping

A diagnostic test used to confirm Down Syndrome by examining chromosomes.

Cognitive Impairment

Common in individuals with Down Syndrome, involving issues like short attention span and delayed language development.

Screening test 1 for DS

A prenatal assessment combining maternal blood tests (e.g. PAPP-A and HCG) and ultrasound measurements to determine risk for Down Syndrome.

Screening test 2 for DS

Involves analyzing cell-free fetal DNA and procedures such as chorionic villus sampling and amniocentesis for diagnosis.

Aneuploidy

An abnormal number of chromosomes, including conditions like Trisomy 21, Trisomy 13, and Trisomy 18.

APP gene

Amyloid precursor protein; its triplication in Down Syndrome is associated with cognitive decline and Alzheimer’s Disease.

Gene dosage effect hypothesis

Suggests that phenotypes of Down Syndrome arise from the overexpression of specific genes on chromosome 21.

Neurogenesis

The process of generating new neurons, which is impacted by various genes in Down Syndrome.

Behavioral management therapies

Non-pharmacological interventions like early intervention and speech therapy aimed at improving outcomes for individuals with Down Syndrome.

Neurotransmitter replacement

A pharmacological approach to restore the balance of neurotransmitters affected in Down Syndrome.

Dendritic spine abnormalities

Changes in neuron structure associated with Down Syndrome, affecting synaptic transmission.

Alzheimer’s disease in DS

An increased risk of developing Alzheimer’s disease in individuals with Down Syndrome, particularly over the age of 40.

Physical symptoms of DS

Includes hypotonia, craniofacial abnormalities, a single deep crease across the palm, and others.

Therapeutic approaches for DS

Include both pharmacological strategies targeting specific gene abnormalities and non-pharmacological therapies for cognitive and physical enhancement.

Gene dosage effect hypothesis

Phenotypes are a direct result of the cumulative effect of the

overexpression of specific genes located in chromosome 21

Amplified developmental instability

Phenotypes are a result of a non-specific disturbance of

chromosome balance due to disrupted homeostasis

OLIG1/OLIG2

Cause excitatory/inhibitory imbalance in DS

DYRK1A

Disturbs stem cell and dendritic development in DS

DSCAM

Inhibits dendritic branching and synaptic

plasticity

APP

Forms Ab plaques

Brain changes

• • Simplified gyri

• Microcephaly

• • Reduced excitatory neuron number

• • Altered neuron morphology

• • Altered brain organization (connectivity):

Synaptic dysfunction

due to Fewer excitatory and

more inhibitory

transmission at the

synapse

Therapeutic approaches: Pharmacological

Restore the excitatory/inhibitory balance using GABA

Increase excitatory neurogenesis

Reduce oxidative stress

gene therapy to normalize DYRK1A, APP, DSCAM, or OLIG1/2 genes