Down Syndrome
Introduction to Down Syndrome
Down syndrome (DS) is a genetic disorder caused by the presence of all or part of a third copy of chromosome 21. It is the most common chromosomal condition diagnosed in the United States, affecting about 1 in every 700 babies born.
Key points:
- Also known as Trisomy 21
- Named after John Langdon Down, who first described the syndrome in 1866
- Leads to variable degrees of intellectual and developmental delays
- Associated with characteristic physical features and health problems
- Life expectancy has increased dramatically in recent decades due to improved medical care
Genetics of Down Syndrome
Down syndrome is caused by the presence of extra genetic material from chromosome 21. There are three types of Down syndrome:
- Trisomy 21 (Nondisjunction): Accounts for 95% of cases. The individual has three copies of chromosome 21 in all cells.
- Translocation: Accounts for about 4% of cases. Part of chromosome 21 attaches to another chromosome, usually chromosome 14.
- Mosaicism: Accounts for about 1% of cases. Only some cells have an extra copy of chromosome 21.
Risk factors for Down syndrome include:
- Advanced maternal age (risk increases after age 35)
- Previous child with Down syndrome
- Carriers of genetic translocation
Clinical Features of Down Syndrome
Individuals with Down syndrome exhibit a wide range of physical and cognitive characteristics. Common features include:
Physical Characteristics:
- Flattened facial profile and nasal bridge
- Upward slanting eyes with epicanthal folds
- Small ears and mouth
- Short neck with excess skin at the nape
- Single palmar crease (simian crease)
- Hypotonia (low muscle tone)
- Short stature
- Small hands and feet
- Clinodactyly (curved pinky finger)
- Wide gap between first and second toes
Cognitive and Developmental Characteristics:
- Mild to moderate intellectual disability
- Delayed language development
- Slower learning and skill acquisition
- Attention deficits
- Impulsive behavior
Diagnosis of Down Syndrome
Down syndrome can be diagnosed prenatally or after birth. Diagnostic methods include:
Prenatal Screening and Diagnosis:
- Non-invasive prenatal testing (NIPT): Cell-free fetal DNA analysis
- First-trimester combined test: Nuchal translucency ultrasound and maternal blood tests
- Quad screen: Second-trimester maternal blood test
- Diagnostic tests:
- Chorionic villus sampling (CVS): 10-13 weeks gestation
- Amniocentesis: After 15 weeks gestation
Postnatal Diagnosis:
- Physical examination: Characteristic features may be apparent at birth
- Chromosomal karyotype: Confirms diagnosis and determines type of Down syndrome
Associated Conditions in Down Syndrome
Individuals with Down syndrome are at increased risk for various medical conditions, including:
- Congenital heart defects (40-50% of cases)
- Atrioventricular septal defect
- Ventricular septal defect
- Patent ductus arteriosus
- Gastrointestinal issues
- Duodenal atresia
- Hirschsprung disease
- Celiac disease
- Endocrine disorders
- Hypothyroidism
- Type 1 diabetes
- Hearing and vision problems
- Congenital cataracts
- Refractive errors
- Conductive and sensorineural hearing loss
- Obstructive sleep apnea
- Atlanto-axial instability
- Increased risk of leukemia
- Early-onset Alzheimer's disease
Management of Down Syndrome
Management of Down syndrome requires a multidisciplinary approach, including:
Medical Management:
- Regular health screenings and follow-ups
- Cardiac evaluation and management
- Thyroid function monitoring
- Hearing and vision assessments
- Gastrointestinal evaluations
- Sleep studies for obstructive sleep apnea
- Immunizations
Developmental Interventions:
- Early intervention programs
- Speech and language therapy
- Occupational therapy
- Physical therapy
- Special education services
Psychosocial Support:
- Family counseling and support groups
- Behavioral interventions
- Social skills training
Prognosis in Down Syndrome
The prognosis for individuals with Down syndrome has improved significantly in recent decades:
- Life expectancy has increased from 25 years in 1983 to 60 years today
- Improved medical care and early interventions have led to better outcomes
- Many individuals with Down syndrome lead semi-independent lives
- Employment opportunities and community integration have expanded
- Quality of life can be high with appropriate support and management
Factors affecting prognosis include:
- Severity of associated medical conditions
- Access to comprehensive healthcare and early interventions
- Family and community support
- Educational and vocational opportunities
Down Syndrome
- What is the most common chromosomal cause of Down syndrome?
Trisomy 21 (an extra copy of chromosome 21) - What percentage of Down syndrome cases are caused by trisomy 21?
Approximately 95% - What is the term for Down syndrome caused by a translocation involving chromosome 21?
Translocation Down syndrome - What percentage of Down syndrome cases are caused by translocation?
About 3-4% - What is the term for Down syndrome where some cells have trisomy 21 and others are normal?
Mosaic Down syndrome - What percentage of Down syndrome cases are mosaic?
About 1-2% - What is the approximate incidence of Down syndrome in live births?
1 in 700 to 1 in 1,000 - Which maternal age group has the highest risk of having a child with Down syndrome?
Women over 35 years old - What is the name of the extra fold of skin at the inner corner of the eye commonly seen in individuals with Down syndrome?
Epicanthal fold - What physical feature of the hands is often associated with Down syndrome?
Single transverse palmar crease (simian crease) - What is the most common congenital heart defect in individuals with Down syndrome?
Atrioventricular septal defect (AVSD) - What gastrointestinal condition is more common in newborns with Down syndrome?
Duodenal atresia - What endocrine disorder is more prevalent in individuals with Down syndrome?
Hypothyroidism - What is the average IQ range for individuals with Down syndrome?
50-70 (mild to moderate intellectual disability) - What chromosome abnormality technique was first used to identify trisomy 21?
Karyotyping - Who first described Down syndrome as a distinct condition in 1866?
John Langdon Down - What is the life expectancy for individuals with Down syndrome in developed countries today?
60 years or more - What type of leukemia has a higher incidence in children with Down syndrome?
Acute myeloid leukemia (AML) - What neurodegenerative condition often develops in individuals with Down syndrome as they age?
Alzheimer's disease - What gene on chromosome 21 is associated with the increased risk of Alzheimer's disease in Down syndrome?
APP (Amyloid Precursor Protein) gene - What is the term for the increased space between the first and second toes often seen in Down syndrome?
Sandal gap - What facial feature is often described as "flattened" in individuals with Down syndrome?
Nasal bridge - What is the term for decreased muscle tone commonly observed in infants with Down syndrome?
Hypotonia - What visual impairment is more common in individuals with Down syndrome?
Refractive errors (myopia, hyperopia, astigmatism) - What hearing problem is more prevalent in individuals with Down syndrome?
Conductive hearing loss - What skeletal condition affecting the upper cervical spine is more common in Down syndrome?
Atlantoaxial instability - What sleep disorder is more prevalent in individuals with Down syndrome?
Obstructive sleep apnea - What autoimmune disorder affecting the thyroid is more common in people with Down syndrome?
Hashimoto's thyroiditis - What is the name of the screening test that combines ultrasound and blood tests to assess the risk of Down syndrome during pregnancy?
First trimester combined screening - What non-invasive prenatal test can detect fetal DNA in maternal blood to screen for Down syndrome?
Cell-free DNA screening (cfDNA) - What invasive diagnostic test can confirm Down syndrome during pregnancy by analyzing fetal cells?
Amniocentesis - What is the recurrence risk for parents who have had one child with Down syndrome due to trisomy 21?
About 1% (slightly higher than the general population risk) - What chromosome region contains the "Down Syndrome Critical Region" (DSCR) thought to be responsible for many Down syndrome features?
21q22 - What is the name of the mouse model used to study Down syndrome, which has three copies of mouse chromosomal regions syntenic to human chromosome 21?
Ts65Dn mouse - What international awareness day is observed on March 21st to raise public awareness of Down syndrome?
World Down Syndrome Day
