Hummel- Clinical Genetics x 2- Leah Flashcards
What makes an anomaly “congenital”?
How common are congenital anomalies?
#1 congenital malformation in the US?
Why is the incidence of NTD decreasing in the US?
- congenital defects: present (not necessarily detected) at birth
- 3% of newborns, up to 7% diagnosed by kindergarten
- # 1 US malformation: club foot
- NTD lowering due to supplementation of all grain products with folic acid
Period during which fetus is most susceptible to anomaly formation?
What percentage of anomalies are actually due to some teratogen?
-Embryonic period (weeks 3-8)
-only 5% due to known teratogens!
(remaining = 25% mendelian, 30% chromosomal, 40% unkown)
What is the term for “the study of abnormal form”?
What three fields of science are involved?
- Dysmorphology
- genetics + embryo + clinical medicine
What is the difference between major and minor anomalies? How common are each?
_____ minor anomalies should raise suspicion for a major anomaly.
- major (effects health, intervention required; 3-5%)
- minor (intervention unecessary; less than 4%)
- 3 or more
What are five kinds of “abnormal” births?
- single defect
- syndrome
- complex
- sequence
- association
Why is the incidence of cleft lip/ palate high in WV?
smoking
Single palmar crease, brushfield spots, epicanthal folds, and clinodactylyl are all _____ that may be assc with _____.
- minor anomalies
- may or may not be assc with DOWNS!
Flat nasal bridge, hydrocele, and syndactyly are all examples of ____.
normal variants (fall to the far end of the spectrum of normal, can serve as clues to other underlying malformation)
What is it called when two toes look like they are stuck together?
What is it called when a digit (usually the pinky) is curved inwards?
- syndactyly (toes)
- clinodactyly (jacked pinky)
What are the three types of problems in morphogenesis?
Which can often be easily reversed?
- malformation
- deformation (easily reversed, i.e. clubfoot)
- disruption
Define malformation.
Give two examples.
Four possible etiologies?
- intrinsically abnormal development
- cleft lip; polydactyly
- genetic, chromosomal, teratogenic, unknown
Define deformation.
Five two examples
- mechanical compression leading to malformation
- club foot, plagiocephaly (abnormally curved head from laying on it)
Define disruption.
Give two examples.
- breakdown of normal development; often caused by ischemia
- amniotic band amputation (missing finger, toes, hand etc), porencephaly (giant stroked out hole in head)
Compare and contrast encephalocele and anencephaly:
these slides are not in ppt, but she had slides on this in lecture…
-anencephaly (no skull; jacked brain; mostly brain stem left)
-encephalocele (small skull defect, part of brain and meninges protrude)
^^ AFP in anencephaly due to leaking fetal fluids.
not ^^ in encephalocele beause membrane = no leaking.
Least severe spina bifida?
moderate?
most severe?
Which is usually NOT due to low folic acid?
(these slides are not in ppt, but she had slides on this in lecture…)
- least: spina bifida occulta (lower spine, not typically caused by low folate, see tuft of hair)
- moderate: myelomeningocele (spinal cord + meninges)
- rachischisis (missing part of spinal cord –> paralysis below that level, often no control of bowel and bladder)
What occurs as a result of MTHFR gene loss?
- ^^ homocysteine (^^ risk clotting, CVD)
- low folic acid (^^ risk NTD if mom is preggos)
Give an example of each of these mutation types:
- lack of development
- hypoplasia
- incomplete closure
- incomplete separation
- incomplete septation
- incomplete migration
- incomplete rotation
- incomplete resolution of early form
- persistence of early location
- lack of development: renal agenesis
- hypoplasia: microcephaly
- incomplete closure: cleft palate
- incomplete separation: syndactyly
- incomplete septation: VSD
- incomplete migration: bladder extrophy
- incomplete rotation: malrotation of gut
- incomplete resolution of early form: Meckels
- persistence of early location: low set ears
What is cloana atresia?
Example of?
How common?
What does it cause at birth?
- narrowing or blockage of the nasal airway by tissue
- incomplete resolution of early form
- most common nasal abnormality in newborn infants
- causes respiratory distress
What is an example of redundant morphogenesis?
Aberrant morphogenesis?
redundant: polydactyly
aberrant: mediastinal thyroid
What may cause deformations in utero?
- uterine pathology i.e. big fibroids –> breech baby –> hip dislocation
- multiple fetuses –> crowding
- uterine malformation i.e. bicornate uterus –> varus legs
What is plagiocephaly again?
Why is the incidence ^^?
How is it corrected?
- assymetric head; example of DEFORMATION
- caused by “back to sleep” campaign
- babies sleep on head a lot –> head gets funny shape
- correct with helmet while babies still have malleable skulls
How is a club foot repaired?
What is it an example of?
- Casting
- deformation
Three etiologies of abnormalities caused by “disruption”
- vascular
- compressive
- tearing
Occlusion of the omphalomesenteric artery causes _____.
What lab abnormality is observed?
What is this an example of?
- gastrochisis
- disruption
- ^^AFP (as opposed to omphalocele, which has a closed membrane = no leakage of fetal fluids)
Drug that commonly causes vascular disruption –> fetal anomalies?
cocaine
A vascular accident leading to disruption in the brain is called?
-The presents similar to what other disease?
-porencephaly
-presents a lot like cerebral palsy
(not fatal)
Describe poland anomaly:
What is it an example of?
-example of disruption
-subclavian artery disruption –> no pectoral muscle
–> smaller boob on that side + ipsi limb defect
(MC on RT side)
Describe a “sequence” in terms of multiple anomalies:
-single abnormality –> CAUSES OTHERS
Classic: POTTERS
Describe the holoprosencephaly “sequence”:
- holoprosencephaly (one brain lobe, no R/L division)
- -> result = close eyeballs or possible cyclopia, midline cleft lip and palate
Sonic hedgehog gene is required for brain development. What activates this gene and what implication does this have on daily practice?
- CHOLESTEROL ACTIVATES SHH.
- If you put a young woman on cholesterol reducing agent, you must also put her on birth control!!!!!
Describe the “robin sequence”
- collagen defect = small chin
causes: abnormal tongue, u shaped cleft palate, airway obstruction
What STARTS the POTTER sequence?
What are the other parts of the sequence?
- Triggered by renal agenesis –> olighydramnios –> fetal compression
- P : pulmonary hypoplasia
- O: oligohydramnios
- T: twisted facies
- T: twisted limbs
- E: low FAT ears
- R: renal agenesis
A combination of anomalies which occur together more frequently than by chance alone:
what is this?
whats the most commonly tested example?
- association
- VATER
What are the components of the CHARGE assc?
- C: coloboma of eye (missing tissue piece)
- H: heart defects
- A: atresia of choanne (nasal passage blocked)
- R: retardation of growth
- G: genital anomalies
- E: ear anomalies
She says these have now been linked to “one chromosome…. so I am assuming this is now a “syndrome” but she talked too fast for me to get the point.
What are the components of VATER assc?
V- vertebral defects
A- anus = imperforate
TE- TE fistula
R- renal defects
What are the components of the MURC assc?
- MU: MUllerian duct anomaly
- R: renal defect
- C: cervical verebral defects
What are: anomalies of several structures that lie in the same body region?
-complex
What is the “OEIS” complex?
- omphalocele
- ecstophy of bladder
- imperforate anus
- spina defect
What are: multiple defects due to a particular chromosomal change?
syndrome
What are the four components of Cornealia de Lange Syndrome?
Whats the cause?
- short
- mentally retarded
- limb
- characteristic facies (i.e. unibrow)
-NIPBL mutation
Retinoic acid:
- before prescribing what should you do?
- what defects does retinoic acid cause?
- two preggo tests each a month apart + be sure the patient has two forms of BC (true story, my derm did this.)
- ear, facial, and CNS abnormalities
What was thalidomide prescribed for?
What kind of deformities can it cause?
- morning sickness
- phocomelia (limb agenesis)
- midline hemangiomas
What do you NEVER EVER tell a patient in genetic counseling?
-That they should not have a baby.
Three types of histories that should be taken at genetic appt?
- Family history (include three generations + any miscarriages/ death + consanguinity)
- Pregnancy history (timing, illness, weight gain, fetal movement, any testing, drugs/exposures)
- Medical history of patient (labor + delivery, milestones, etc)
2 Key components of PE at genetics appt?
- Observe/ look for ASSYMETRY.
- Measure anything that can be measured.
2 genetic disorders that involve defective “methylation”?
- Prader Willi
- Angelmans
Gingival Hyperplasia and corneal clouding are assc with?
-Hunters
Telephone reciever femurs and inadequate lungs are assc with? Gene involved?
- Thanatophoric Dwarfism
- FGFR3= most common gene involved in all types of dwarfism
When should a family or individual be referred for genetic counseling?
- Prior to conception
- A soon as possible for newly diagnosed patients
Key component to communication in genetic counseling?
-provide family with written report after the session to be sure they can review
