Epidemiology
Why is the use of Atropine (e.g., in ophthalmology or anesthesia) treated with caution in patients with Down Syndrome?
Individuals with DS exhibit hypersensitivity to cholinergic antagonists, leading to potentially dangerous tachycardia.
A child with Down syndrome has a karyotype 46,XX,der(14;21)(q10;q10),+21.
Question: What is the recurrence risk in the next pregnancy if the mother is the carrier?
~10–15% if mother is Robertsonian translocation carrier (14;21)
Patient A and Patient B comes to the family planning clinic to discuss expanding their families.
Patient is 24 years old. She had her first child 2 years ago and he has Down Syndrome.
Patient B is 40 years old and has never had a baby.
Which patient is most at risk of having a child with Down Syndrome?
Patient A
Non-invasive Prenatal Testing (NIPT)
10
Is there a curative treatment for Down syndrome? If not, what is the cornerstone of management?
No curative treatment; early intervention and multidisciplinary supportive care is the cornerstone.
Which seizure type is most commonly seen in adolescents with Down syndrome?
myoclonic
This is the least common cause of Down Syndrome. It accounts for 1-2% of cases.
Mosaicism
Which congenital heart disease is pathognomonic for Down syndrome and why is it embryologically linked?
Complete atrioventricular septal defect
(Endocardial cushion defect)
How quickly are results available from the FISH test?
24-48 hours
List 2 early intervention and developmental support methods.
Speech therapy
Physical therapy
Occupational therapy
Behavioural therapy
Special education programs
15-20% of people with Down Syndrome develop ____ in middle age.
a) Hypothyroidism
b) Alzheimer's Disease
c) Depression
d) Behavioural problems
b) Alzheimer's Disease
What is nondisjunction and in which of the causes of Down Syndrome is it implicated?
Nondisjunction is the failure of a pair of homologous chromosomes to separate at anaphase so that both chromosomes of the pair pass to the same daughter cell.
Trisomy 21
State a dysmorphic feature of the hands OR feet present in a patient with Down Syndrome.
Sandle-toe deformity (space between big toe and the one beside it)
Short broad hands
Palmar crease
Which ophthalmological finding is considered a common, benign iris feature in children with Down Syndrome?
Brushfield spots
These are small, white-grayish spots on the periphery of the iris caused by connective tissue aggregation.
Why is routine growth hormone therapy not recommended in Down syndrome despite short stature?
Limited cognitive benefit, potential risk of leukemia, and growth failure is largely constitutional.
Key intellectual disability gene:
DYRK1A
In mosaic Down syndrome, which tissue gives the highest diagnostic yield if blood karyotype is normal?
Best tissue for mosaicism detection:
Skin fibroblasts (or buccal mucosa)
In a patient with Down Syndrome and suspected transient myeloproliferative disorder (TMD), which specific genetic mutation is almost universally present in the leukemic blasts?
GATA1 mutations are hallmark features of both TMD and subsequent AMKL in children with Trisomy 21.
Which immunological defect explains recurrent respiratory infections in Down syndrome?
T-cell dysfunction with reduced naïve T cells
A child with Down syndrome and AV canal defect develops early pulmonary hypertension. What is the key treatment strategy?
Early surgical correction of AV canal defect before irreversible pulmonary vascular disease develops.
Which neuropathological change explains early-onset Alzheimer disease in Down syndrome?
APP gene overexpression → β-amyloid deposition
What is the molecular mechanism by which increased maternal age predisposes to nondisjunction?
Cohesin protein degradation → spindle assembly checkpoint failure
According to the AAP guidelines, at what age should a child with Down Syndrome receive their first screening polysomnography (sleep study) regardless of symptoms?
4 yrs, The high prevalence of obstructive sleep apnea (up to 70%) necessitates a baseline study by this age even if the child is asymptomatic.
Hashimoto's thyroiditis is very common in DS, appearing as early as infancy or later in childhood.
What is the mechanism of increased autoimmunity despite immune deficiency?
Autoimmunity in Down syndrome occurs due to defective central and peripheral immune tolerance caused by thymic hypoplasia, impaired regulatory T cells, and interferon-mediated immune dysregulation.
Why must chemotherapeutic drug dosing be modified in children with Down syndrome treated for acute leukemia?
Children with Down syndrome have increased sensitivity to chemotherapy due to altered folate metabolism and increased apoptosis, increasing toxicity risk.