Pathophysiology
Maternal age at which risk for Down Syndrome in offspring increases
What is pregnancies after 30
Name 3 phenotypic changes commonly seen in patients with Down Syndrome
- single palmar crest
- small, low set ears with overfolded upper helices
- short stature
- brushfield spots
- flattened occiput
- hypotonia
- flattened nasal bridge
etc.
Explain karyotype of our patient
- 46, XX/47, XX +21
- mosaicism
Identify the prevalence of Down Syndrome
- 1 in 700 live birth
- 95% affected have 47, XX or XY 21+
Identify pertinent ultrasound findings
- edema in nuchal fold
- excess amniotic fluid
- splaying toes
- femur length decreased
Identify GI complications associated with Down Syndrome
- atresia of small bowel
- atresia of esophagus
Explain the result of trisomy from meiosis nondisjunction v trisomy from early embryonic development
- full trisomy 21 from meiosis or gametogenesis error
- early embryonic development is more likely to result in mosaicism
Explain the significance of Robertsonian Translocation carrier parent
Maternal carriers of Robertsonian translocations are at a higher risk for producing gametes with extra gene dosage chromosome with translocation.
Identify risks associated with amniocentesis
- spontaneous abortion
- misdiagnosis
Identify cardiac defects associated with Down Syndrome
- atrioventricular septal defects
- ventricular septal defects
- atrial septal defects
- tetralogy of Fallot
Describe or draw gametogenesis
Image
Describe timeline and significance of each of the screening and tests done for diagnosis (fetal ultrasound, cell free DNA, amniocentesis, quad screen)
- 10 week Cell Free DNA
- 18 week quad screen
- 20 week ultrasound
- after 15 weeks amniocentesis
Identify the neurological/intellectual deficits associated with Down Syndrome
- after the age of 40 neuropathologic changes similar to Alzheimer's develops
- intellectual deficits of varying degree
Identify what step gametogenesis is likely to fail in each parent and which parent usually passes on the extra chromosome
- maternal meiosis is cause in 90% of cases
- occurs in meiosis I
- paternal meiosis is cause in about 10% of cases; nondisjunction occurs in meiosis II
Describe or draw nondisjunction
Image
- Down Syndrome: Low AFP, low estriol, high Hcg, high inhibin A
- Turner's: Decreased AFP, Decreased estriol, very high Hcg, very high inhibin A
- Edward's: normal AFP, low estriol, very low hCG, normal inhibin A
- Patau's: Increased AFP, Normal estriol, normal hCG, normal Inhibin A
Identify types of cancer patients with Down Syndrome are most likely to develop
- 20-fold increased risk of developing lymphoblastic leukemia
Compare likelihood and phenotype of mosaicism v full trisomy 21
- only 1% are mosaics
- mosaicism phenotype is more variable and less severe