DEVELOPMENTAL GENETICS AND DYSMORPHOLOGY

What is dysmorphology?

Study of congenital birth defects that alter the shape or form of one of more parts of the body of a child

What are the three major categories for birth defects?

Malformations, deformations, and disruptions

What is a malformation?

due to INTRINSIC abnormalities in one of more genetic programs operating in development

What are deformations?

Due to EXTRINSIC factors impinging physically on the fetus during development 

What are disruptions?

Due to destruction of normal fetal tissue

What is an example of a malformation?

Greig cephalopolysyndactyly

What causes greig cephalopolysyndactyly?

Loss of function mutation in GLI3

What is the most common cause of birth defects?

Multifactorial

What are the 5 main causes of birth defects in order?

Multifactorial, chromosome imbalance, single gene defects, copy number variants, and teratogen

What is an example of a deformation?

Arthrogryposes

What is the cause of arthrogryposes?

Constraint of fetus dude to twin or leakage of amniotic fluid

What is an example of a disruption?

Amnion disruption

What causes amnion disruption?

Trauma, constriction rings

What is pleiotropy?

Birthday effect resulting from underlying causative agent than may result in abnormality in more than one organ system 

What is a syndrome?

Causative agent causes multiple abnormalities at the same time

What is a sequence?

Causative agent affects one single organ and then a domino effects occurs

What is an example of a syndrome?

Branchio-oto-renal dysplasia syndrome

What is the cause of Branchio-oto-renal dysplasia syndrome?

Mutation in EYA1

What is an example of a sequence?

Robin sequence

What causes robin sequence?

Restriction of jaw growth before 9 week gestations causes tongue to lie more back interferes with normal closure of mouth, causing cleft palate

What is an example of embryological development?

Proteius syndrome?

What causes proteius syndrome?

Somatic mosaicism for de novo activates mutations in AKT1

What happens days 7-12 od human embryogenesis?

Implantation in endometrial wall and gastrulation

What is the endoderm?

Cells lining

What is the mesoderm?

Supportive functions

What is the ectoderm?

Central and peripheral nervous systems and skin

What happens during weeks 4-8 of embryogenesis?

Imitation of nervous system and establishment of basic body plan

What is a stem cell?

Cell capable of both self renewal and proliferation and differation

What is specification?

Get characteristics due to influence of environment

What is determination?

Irreversible acquires

What is fate?

Ultimate destination

What is regulative development?

Early in development, cells are equivalent

What is mosaic development

later in development, loss of portion causes failure of development

What happens to development plasticity of the embryo with time?

declines

What causes conjoined twins?

Later embryo cleaves events that occur during mosaic development

What controls development by controlling expression of other genes?

Transcription factos

What is an example of regulation by transcription factors?

Synpolydactyly

What causes synpolydactyly?

Complete dominance, gain of function

What is a morphogen?

substance in a localized region that diffuses out to form concentration gradient

How must cells organize themselves?

With respect to position and polarity in their microenvironment

What is an example of how cells must organize themselves and why?

Polycystic kindey disease, loss of function of protein to form cilia so cells can sense fluid flow

What is an example of programmed cell death?

DiGeorge syndrome