Genetics E1- Congenital Abnormalities

What term refers to the formation of a human being?

Morphogenesis

What stage of embryotic development is from fertilization to implantation?

Pre-embryonic

What stage of embryonic development is from implantation through gestational week 8?

Embryonic

What stage of embryonic development is from week 8 through birth (parturition)?

Fetal

What is a morula?

Solid ball of cells (16-32 cells) formed after zygote undergoes rapid cellular division (cleavage) 3-4 days after fertilization

What is a blastocyst?

Hollow sphere in the morula from fluid accumulation that consists of a clump of cells (inner cell mass or ICM) & a ring of flattened cells (trophoblast)

What part of the blastocyst eventually becomes the embryo?

ICM

What part of the blastocyst further develops into the embryonic portion of the placenta that supplies nutrients to & removes wastes from the embryo?

Trophoblast

When does implantation of the blastocyst to the uterine wall occur?

6-7 days after fertilization

What prevents implantation from occurring?

*unimplanted blastocysts are absorbed by endometrium or expelled during menstruation

Endometrial infx, IUD, morning after pill, certain genetic mutations

What occurs by day 14 after fertilization if implantation does occur?

Endometrium grows over blastocyst → endometrial cells produce paracrines such as PGs to promote local changes in endometrial tissue

After the amnion is formed from a layer of separated cells from the ICM, what do the cells of the ICM then differentiate into?

*marks the beginning of organogenesis

3 distinct germ layers: ectoderm, mesoderm, & endoderm

What is the study of abnormal development?

Teratology

What are teratogens?

Anything capable of disrupting embryonic or fetal development & producing malformations

What is the critical period for teratogenic effects?

3-16 weeks of gestation

What teratogen was used to treat morning sickness in the 1950s but was removed from the market due to causing phocomelia?

Thalidomide

What is phocomelia?

Shortened limbs resembling flippers of a seal due to lack of some or all of the long bones in a fetus

What teratogen is used for the treatment of cystic acne but can cause fetal malformations involving the cranium, face, heart, CNS, and thymus?

Isotretinoin

What is required when a patient is starting Isotretinoin (Accutane)?

hCG before initiation & periodically, and must use 2 forms of birth control

What 5 congenital infections have similar presentations, including rashes, ocular findings, microcephaly, hydrocephalus, and abnormally shaped gyri & sulci?

TORCH: Toxoplasmosis, Other (syphilis), Rubella, CMV, HSV

What virus is an arthropod-borne flavivirus that is transmitted sexually & by mosquitoes and causes miscarriage, microcephaly, developmental delays, myelitis, meningoencephalitis, & GBS?

Zika virus

What abnormalities are seen with fetal alcohol syndrome?

Growth retardation, CNS dysfunction, mental deficiency, emotional disorders, & characteristic facial dysmorphology such as short palpebral fissure length, smooth philtrum, & thin upper lip

Why is the term fetal alcohol effect also used to describe fetal alcohol syndrome?

Not all children adversely affected by maternal alcohol abuse exhibit the entire spectrum of abnormalities

What risks are associated with smoking while pregnant?

Low birth weight (2x risk), SGA newborn (2.5 fold), subfertility, spontaneous abortion, placenta previa & abruption, and preterm delivery

What causes most of the adverse effects to the offspring with maternal cocaine use?

Vasoconstrictive & hypertensive effects of the drug

What is the MC cocaine-related pregnancy complication?

Placental abruption

What causes an isolated limb-reduction defect (ex- absence of a hand)?

Disruption of vascular supply at a critical time during the development of the limb bud

What are 3 factors known to affect the likelihood and extent of teratogenesis?

Dosage, time of exposure, & genotype of the embryo

What is the leading preventable cause of acquired intellectual disability?

Fetal alcohol syndrome