Fetal Genetic, Metabolic, Drug Exposures Flashcards
Advanced paternal age
- Autosomal dominant (achondroplasia; Apert, Waardenburg, Crouzon, Pfeiffer, and Marfan syndromes; Neurofibromatosis; Osteogenesis imperfecta)
- Microdeletions
- More copy number variants
- X-linked (“grandfather effect” more de novo spontaneous germline mutations in X’s there but daughters unaffected and instead affects daughter’s male offspring)
- Aneuploidy —— sooooooome effect but nothing like mom. Why not? Aneuploid sperm not likely to be the one that wins out at fertilizing the egg
- Nonetheless slight assoc in Tri21 and Klinefelter’s
Microarray misses
- Balanced rearrangements
- Translocations / inversions
- Single gene mutations
- Uncommon ethnicity combinations? (Don’t know what that note meant)
Genetic heterogeneity vs pleitropy
More than one gene causes same phenotype
VS
Single gene causes multiple phenotypic expressions
Mitochondrial inheritance
- Leber’s Hereditary Optic Neuropathy
- Leigh Syndrome
- Myoclonic epilepsy with ragged red fibers
- Pigmentary retinopathy
Repeat diseases
- Fragile X
- Huntington’s
- Myotonic dystrophy
- Friedrich Ataxia
- X-linked spinal/bulbar muscular atrophy (Kennedy Disease)
- Machado-Joseph
- Spino-cerebellar ataxia
Trisomy 21; how many extra chromosome vs robertsonian vs mosaic
95% trisomy, 4% robertsonian, 2% mosaic
Deformation vs sequence vs association vs syndrome vs disruption
- Deformation
- Genes: normal
- Environment: abnormal
- Sequence
- One insult => everything
- Association
- Anomalies occur together, but don’t know why
- Syndrome
- Disruption
- Specific insult to genetically normal tissue
Prader Willi
- 15 is maternally / paternally imprinted?
- Due to maternal / paternal UPD?
- Genetic material that is present is entirely maternal / paternal?
- % due to UPD vs due to deletion?
Maternally imprinted
Maternal UPD
Maternal is all that’s present
Only 20-30% actually UPD; most of the time just a big deletion on the paternal chromosome 15.
Angelman
- 15 is maternally / paternally imprinted?
- Due to maternal / paternal UPD?
- Genetic material that is present is entirely maternal / paternal?
- % due to UPD vs due to deletion?
Paternally imprinted
Paternal UPD
Paternal is all that’s present
Only 5% actually UPD; most of the time just a big deletion on the maternal chromosome 15.
CF carrier frequency. Highest (and how much)? Lowest (and how much)?
Europeans and Ashk Jewish 1/25. Asian 1/90.
Residual CF risk after negative result. Highest and lowest?
S Europeans 1/80 still. Lowest Ashk Jewish 1/833! (Middle of the road N Euro 1/240)
Detection rates Trisomy 21 by screen
1st tri serum 60% NT only 66% 1st tri combo 82% 2nd tri serum 81% Serum integrated 86% FULL integrated (report only after ALL done) 95% Stepwise sequential (offer dx for 1st tri >1:50) 95% Contingent sequential (High/Intermed/Low) 92%
Trisomy 18 detection rate
90% with 1st tri screen
Enzyme deficiency Canavan Gaucher Neimann Pick Tay-Sachs ...plus which one's treatable?
Metabolic Disorder Mnemonics
- Pick my Nose with my Sphinger!
- tAy sachs = beta hex A
- Gaucher = Glucocerebrosidase which can be Grown (in a lab)
- CanAAvan = AspartoAcylase
Williams
- Facies description
- CV finding
- Microdeletion 7q11.23
- Broad forehead, short nose, broad full cheeks, wide mouth full lips
- CV problems: supra-valvular aortic stenosis
Osler-Weber-Rendu
telangiectasia, epistaxis, AV malformations
Treacher-Collins
Mandibulofacial dysostosis + EARS
Myotonic dystrophy
- Also a repeat issue (CTG)
- LOW penetrance
- Fetus: POLYHYDRAMNIOS. Myotonia is absent in congenital form. Talipes also common.
- Mom: PTB, prolonged labor. Poor voluntary assistance 2nd stage.
- AVOID DEPOLARIZING MUSCLE RELAXANTS
Thrombocytopenia Absent Radii (TAR) syndrome
- Inheritance?
AutoR
Pentalogy of Cantrell
- (speak in CODES mnemonic)
- Cardiovascular Malformations
- Omphalocele
- Diaphragmatic defect
- Ectopia cordis
- Sternal defect
