1802526
| Question | Answer |
| CF Screening | Offer to all women of reproductive age. Testing panels vary by number of mutations tested for and detection rate based on ethnicity. |
| SMA screening | Caused by mutation in SMN1 gene, 95-98% have homozygous deletion of exon 7. Gene can replicate itself and individuals have 1,2, or 3 copies. SMN2 gene not causative but can affect severity. Carrier screening reports SMN1 exon 7 copy number - 1 copy carrier, 2 copies reduced risk, 3 copies markedly reduced risk. |
| Fragile X Screening | Carrier frequency of premutation ~1/250 Screening recommended for women with POF or family hx POF/FrX Common CGG repeat <45 Intermediate 45-54 Premutation/Carrier 55-200 Full mutation >200 Interrupted repeats can have a decreased risk of expansion. |
| Hemoglobinopathy Screening | CBC and hemoglobin electrophoresis. If anemia with low MCV and normal iron status and southeast Asian ancestry, even with normal hgb electrophoresis evaluate for alpha-thalassemia. |
| Sickle Cell Disease Screening | Normal MCV Decreased HbA Increased HbS/C Normal HbA2 |
| Beta-thalassemia screen | Low MCV Slightly decreased HbA Increased HbA2 |
| Alpha-thalassemia | Low MCV Normal Hgb elctrophoresis Rule out iron deficiency |
| Increased NT | 3 mm (95%) or 3.5 mm (99%) between 10-14 weeks. Normal 50-70% risk reduction from maternal age for aneuploidy. Increased - risk is 1/10 for DS with NT of 3.9 mm, increased for structural anomalies, genetic syndromes, adverse outcome. |
| Open Neural Tube Defect (Spina Bifida) | Very high AFP Normal uE3 Normal hCG |
| 1st trimester screen First look | 11-14 weeks GA NT measurement PAPP-A and hCG 85% for DS, 60% for T18 False positive 5% |
| Down Syndrome | First Trimester Screen: High nuchal translucency, low PAPP-A, high hCG Second Trimester Screen: Low uE3, low AFP, high hCG, high Inhibin A US findings: NT LR 11-18.5, echogenic bowel LR 5.5-6.7, absent/hypoplastic nasal bone LR 80 |
| Trisomy 18 | First Trimester Screen: High nuchal translucency, low PAPP-A, low HCG Second Trimester Screen: very low uE3, low AFP, very low HCG Common US findings: agenesis CC, meningomyelocele, ventriculomegaly, cystic hygroma, cardiac anomalies, diaphragmatic hernia, omphalocele, clenched hands with overlapping digits, IUGR, polyhydramnios |
| 2nd Trimester Screen | Quad Screen: AFP, hCG, uE3, Inhibin A 15-18 weeks GA Risk for DS, T18, neural tube defects 80% detection rate for all 3 5% false positive rate |
| Fetal Demise | Low hCG, low uE3 If recent high AFP. If older, low AFP. |
| Smith Lemli Opitz | Very low uE3 |
| X-linked Ichthyosis | Very low uE3 |
| Congenital Finnish Nephrosis | Very high AFP |
| Placental Mosaicism | 1-2% of placentas can have different chromosome makeup than fetus |
| Blastocyst | Early embryonic stage. The cells on the outer surface of the morula secrete fluid to form a fluid-filled internal cavity within which there is a separate group of cells, the inner cell mass (embryoblast) that will form the embryo, and an outer cell mass (trophoblast) that will form the placenta. |
| Gastrulation | Conversion of the inner cell mass (embryo blast) into a bilaminar and then trilaminar disc. Occurs in the 2-3rd week of gestation. |
| Ectoderm | Forms central nervous system, peripheral nervous system, epidermis (hair and nails, subcutaneous glands, dental enamel. |
| Mesoderm | Forms connective tissue, cartilage and bone, smooth and striated muscle, cardiovascular system, urogenital system. |
| Endoderm | Thymus, thyroid, GI system, liver, pancreas. Linking of pharynx, thyroid, and parathyroids. |
| Neural tube | Formed from neural crest cells that migrate to form the sensory ganglia, sympathetic nervous system, pigment cells, bona and cartilage in parts of the face and branchial arches. |
| BMP (Bone morphogenetic proteins) | Involved in patterning the mesoderm. Signaling involved in dendritogenesis and axonal transport. Part of TGF-beta family of protein signals. |
| TGF family signaling (Transforming growth factor) | Actively involved in broad range of cellular and developmental processes: cell cycle, cell migration, cell size, gastrulation, axis specification, and metabolic processes. |
| Notch-Delta Signaling | 'oscillation clock' - a precise, temporally defined wave of cycling gene expression that sweeps from the tail-bud region in a rostral direction and has a key role in the process of defining somite boundaries. Mutated genes in pathway associated with presenile dementia, spondylocostal dysostosis, Alagille syndrome. |
| Sonic Hedgehog gene (SHH) | Produced by the notochord and floor plate of developing neural tube generating a gradient that induces and organizes the types of cells and tissues in the developing brain and spinal cord. Produced by limb bud creating zone of polarizing activity establishing posterior side of developing limb and asymmetrical pattern of digits. After cleavage and modification by adding cholesterol moiety, the protein binds with receptor patched (ptch), a transmembrane protein. Once ptch is bound by shh, it stops inhibiting transmembrane protein smoothened (smo) and signaling cascade is activated with intracellular targets in the GLI family of transcription factors |
| Homeobox (HOX) Genes | Encode transcription factors with a conserved DNA-binding homeodomain. 40 Human HOX genes in 4 clusters on 4 chr Function: Specify anterior-posterior axis, determine identity of individual vertebrae and somites, determine regional identity along axes of developing limbs. Genomic organization within clusters correlates with function during development. Incorrect expression results in major structural abnormalities. |
| Paired-box (PAX) Genes | Highly conserved sequence 9 PAX genes Role in developing nervous system, vertebral column |
| SRY-Type HMG Box (SOX) Genes | Family of genes with homology with SRY by sharing 79 AA domain known as high-mobility group (HMG) box. HMG domain activates transcription by bending DNA so regulatory factors can bind with promoter regions. Expressed in specific tissues during embryogenesis. |
| T-box (TBX) Genes | TBX genes dispersed throughout the human genome, some in small clusters. Role in specification of the paraxial mesoderm and notochord differentiation. |
| Fibroblast growth factor (FGF) receptors | FGFs play key roles in embryogenesis - cell division, migration, differentiation. FGF receptors are transmembrane tyrosine kinase receptors with 3 components (extracellular region with Ig-like domains, transmembrane segment, 2 intracellular TK domains) |
| 1st Pharnygeal arch, cleft, pouch | Arch - Jaw and muscles of mastication Cleft - external auditory meatus Pouch - middle ear apparatus |
| 2nd Pharnygeal arch | hyoid apparatus, muscles of facial expression |
| 3rd Pharnygeal Pouch | Thymus parathyroids |
| 4th pharyngeal pouch | parathyroids |
| Apical Ectodermal Ridge (AER) | Thickened ectoderm at limb tip. Produces growth signals such as FGF4 and FGF8 which maintain further growth and establish proximo-distal axis. Requires TP63 expression to sustain. |
| Zone of Polarizing Activity | Posterior margin of developing limb bud Determine tha anterior posterior axis. Signals SHH, FGF genes, GLI3, CBP |
| Partial Hydatidiform Mole | 69 Chromosomes Fertilization by two sperm (dispermy) or duplication of the haploid sperm chromosome set by endoreduplication. Rarely survive to term. Placenta consists of proliferating disorganized mass. |
| Complete Hydatidiform Mole | 46 chr exclusively paternal in origin. Fertilization of an empty ovum by two sperm or by a single sperm that undergoes endoreduplication. Abnormal pregnancy with placenta of proliferating disorganized mass. Potential to undergo malignant change into invasive choriocarcinoma. |
| Monozygotic Twinning | 1 in 300 births Division before 3 days - dichorionic Division 3-7 days - monochorionic diamniotic Division after 7 days - monoamniotic twins Division after 14 days - can result in conjoined twins (75% female) |
| ACE Inhibitors | Renal Dysplasia |
| Chloroquine | Chorioretinitis, Deafness |
| Diethylstilbestrol | Uterine malformations, vaginal adenocarcinoma |
| Lithium | Cardiac defects (Ebstein anomaly) |
| Phenytoin Teratology | Cardiac defects, cleft palate, digital hypoplasia. Higher risk of craniofacial anomalies with maternal EPHX1 polymorphisms |
| Retinoids | Ear and eye defects, hydrocephalus |
| Streptomycin | deafness |
| Tetracycline | dental enamel hypoplasia |
| Valproic acid Teratology | Increased risk of spina bifida, cleft lip/palate, craniofacial abnormalities. |
| Warfarin | nasal hypoplasia, stippled epiphyses |
| Thalidomide Teratology | Previously used as sedative. Greatest sensitivity days 20-34 post-fertilization. Patterns of malformations: duane's anomaly, coloboma, anophthalmia, microtia, extra teeth, renal agenesis,, duodenal and anal atresia, phocomelia, deficiency of thumb, hemangioma |
| Rubella Teratology | Damages 15-25% of all babies infected during 1st trimester Microcephaly, cataracts, retinitis, cardiac defects (PDA, peripheral pulmonary artery stenosis) Greatest sensitive less than 8 weeks. |
| Cytomegalovirus | Infection in 1st trimester causes damage in 5% of infected pregnancies. Chroioretinitis, deafness, microcephaly. |
| Toxoplasmosis | maternal infection during 1st trimester leads to 20% risk that fetus will be infected. Hydrocephalus, microcephaly, cataracts, chorioretinitis, deafness |
| Varicella Zoster | microcephaly, chorioretinitis, skin defects |
| Syphilis | hydrocephalus, osteitis, rhinitis |
| Ionizing Radiation | Microcephaly, ocular defects Most sensitive 2 to 5 weeks post-conception. |
| Amniocentesis | 10-20 mL of amniotic fluid. Done at 16-20 weeks GA. Pellet of cells and supernatant fluid. Supernatant fluid - alpha fetoprotein. Cell pellet - fetal skin, urinary tract epithelium. 0.5-1% risk of miscarriage. |
| Chorionic Villus Sampling | 11-13 weeks gestation. Aspiration of chorionic villus tissue. 1-2% risk of miscarriage. small risk hemangioma and limb reduction defects |
| Nuchal Translucency | Accumulation of fluid at back of the neck. Leads to detailed fetal heart scanning and fetal karyotype. 3 mm -> 17% have aneuploidy >5.5 mm -> 15% Cardiac anomalies 6mm -> inc risk fetal death |
| Echogenicity of fetal bowel | Likelihood ratio 5.5-6.7 for trisomy 21 Association with 1-2% risk of cystic fibrosis (prenatal equivalent of meconium ileus) |
| Prenatal Anencephaly | Very high AFP Very low uE3 Normal hCG |
| Genetic Causes Infertility | CF - Congenital bilateral absence of vas deferens (1-2% infertile men), obstructive azoospermia, usually 1 severe & 1 mild mut Myotonic dystrophy - male infertility with oligoazoospermia from sclerosis of seminiferous tubule Kennedy disease Kartagener Syndrome - immotile cilia Balanced Translocations - 3+ SAB 9.2%, 10+ failed IVF cycles 3.2% |
| Maternal hyperphenylalaninemia Teratology | Teratogenic effects differs with higher exposure. Mental retardation, microcephaly, congenital heart disease, low birth weight. |
| Accutane Teratology (Isotretinoin; 13-cis-retinoic acid) | 35% major malformations: conotruncal heart defects, cranial nerve palsies, absence of the cerebellar vermis, moderate to severe MR. 25% no malformations with MR |
| Coumadin Teratology | Increase in - defects in nasal cartilage - stippling epiphyses - shortened fingers |
| Fragile X Infertility | Fragile X - premutation females (55-199 repeats) leads to premature ovarian insufficiency/failure Hypergonadotrophic hypogonadism, diminished follicle recruitment and growth Toxic effect increased mRNA. Among sporadic POI 2-5% premutation, with one relative with POI 12-14% 5% spontaneous conception rate. |
| Methotrexate Teratology | Period of greatest sensitivity: weeks 6-8 |
| Ovarian Dermoid | 46,XX Ovarian tumor trying to develop all cell lines of fetus All maternal imprinting. |
| Choroid Plexus Cysts | Marker for Trisomy 18 |
| Morula | A compact ball of 16 cells produced after four cell divisions of the zygote. |
| Alpha-fetoprotein | Fetal glycoprotein produced mainly in the liver secreted into the fetal circulation and excreted through the kidneys. Enters the maternal blood stream. Need to compare to normal range for gestational age. Elevation - open neural tube defect, fetal blood contamination, fetal death, twin pregnancy, ventral wall defects, congenital nephrosis, incorrect GA |
| Trisomy 13 | First trimester Screen: high nuchal translucency, low PAPP-A, low HCG Second trimester screen: low uE3, low AFP, low hCG Common US findings: CNS (holoprosencephaly, agenesis of CC, meningomyelocele, microcephaly), cleft lip/palate, midface hypoplasia, cyclopia, microophthalmia, nuchal thickening, cardiac anomalies, omphalocele, echogenic bowel, echogenic kidneys, radial aplasia, polydactyly |
| cell-free fetal DNA | 2-10% cell free DNA in maternal blood is derived from placental trophoblasts. Used for aneuploidy, fetal sex, Rh locus |
| Trisomy 21 | Only 20% conceptus trisomy 21 liveborn Common US findings: ventriculomegaly, brachycephaly, nuchal thickening, CHD, duodenal atresia, echogenic bowel, renal pyelectasis, shortened femur/humerus, clinodactyly of the 5th digit, sandalfoot |
| Azoospermia | No sperm in ejaculate 1-2% infertile men: Congenital bilateral absence of the vas deferens (CBAVD) - obstructive azoospermia. CBAVD with renal abnl - get renal US, nl sweat chloride. 10-15% AZF (azoospermia factor) |
| Oligospermia | Sperm count <20x10^6/mL; Severe <10x10^6/ml 4.6% abnormal karyotype (XXY, robertsonian, or reciprocal translocation) |
| Assisted Reproductive Technologies | ICSI: 8.6% major anomaly by 1 yo 1.6% multiple anomalies by 1 yo IVF: 9% major anomaly by 1 yo 2% multiple anomalies by 1 yo Gen Pop: 4.2% major anomaly by 1 yo 0.5% multiple anomalies by 1 yo |
| Cystic Hydroma | >50% risk aneuploidy Most common 45,X |
| Percutaneous Umbilical Blood Sampling (PUBS) | US guidance. Fetal umbilical vessel sampled with 22 gauge needle. Advantage: fetal hematology and serology. Disadvantages: 1-2% risk of fetal loss, later in gestation >18 weeks. |
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