Congenital malformations& dysmorphic syndromes Flashcards
How can we classify malformation
- Major: causes significant medical or cosmetic problems( spina bifida) or cleft palette
- Minor: Of no medical significance e.g accessory nipple, single palmar crease
- Single malformation: often multifactorial
- Multiple: often genetic
What is amniotic band syndrome?
- Occurs when the unborn baby (fetus) becomes entangled in fibrous string-like amniotic bands in the womb, restricting blood flow and affecting the baby’s development
- If a band wraps tightly around a limb, the limb can actually be completely amputated. If the band is across the baby’s face it can cause cleft palate.
Outline chromosome rearrangements
- ) Number
- Aneuploidies ( chrom number not divisible by the haploid number)
- Polyploidies (multiple sets of chromosome) - ) Structure
- Balanced translocations
- Unbalanced: deletions;duplications;inversions;translocations
Often associated with problems
Outline trisomy 21
- Downsyndrome
- Intellectual disability: mild to moderate learning difficulties
- Cardiac defects eg AVSD can be primary trisomy 21 or a translocation 46,Xn, der(14;21) (q10;q10) +21
Outline trisomy 18
- Edward syndrome
- Severe mental disability
- Dysmorphic: micrognathia; prominent occiput; clenched overlapping fingers; prominent heels& rocker-bottom feet; cardiac defects
- Primary trisomy 18 47,XX +18 or 47 XY +18
Outline trisomy 13
- Patau syndrome
- Severe mental disability
- Dysmorphic: cleft lip, cleft palate; holoprecencephaly; postaxial polydactyly; renal abnormalities; cardiac defects
- 45% die within 1 months, 85% withing 1 year
- primary trisomy 47,XX+13
- Unbalanced translocation 46, Xn, +13, der(13,14)(q10;q10)
Outline del22q11.2
- deletion of a section of chromosome 22
- CATCH 22/DiGeorge syndrome/ velocardiofacial syndrome
- CHD (conotruncal anomaly)
- Cleft lip and/or palate
- Absent thymus
- Absent parathyroid glands
- Dysmorphic features
- Learning difficulties
What is williams syndrome
- del17q11
- developmental delay
- very happy & sociable
- May have congenital heart problems
Outline the features of del16p11.2
- Learning difficulties
- ASD
- seizures
- schizophrenia, bipolar,depression
- Obesity in young adults
- Also unaffected individuals
- 525kb deletion, containing 25 genes
Using the example of Noonan syndrome, explain how mutations in genes which function within the same pathway may cause similar but distinct clinical phenotypes
-Noonan syndrome is caused by changes in one of several autosomal dominant genes.
-Noonan syndrome is a disorder that involves unusual facial characteristics, short stature, heart defects present at birth, bleeding problems, developmental delays, and malformations of the bones of the rib cage.
Some phenotypic overlap with:
-Neurofibromatosis type 1: especially NF1 & valvular pulmonary stenosis( similar Noonan like facies- aka Watson syndrome)
-Cardio-facial-cutaneous syndrome: more severe learning difficulties & sparse hair/lack of eyebrows
-Costello syndrome: severe developmental delay & learning difficulties& increased risk of malignancy
What factors affect gene expression and penetrance
- Modifier genes
- carcinogens
- Hormonal/reproductive factors
- Response to DNA damage
Outline Duchenne muscular dystrophy
- onset age 3-6yrs
- Progressive weakness
- Pseudohypertrophy of calf muscles
- Spinal deformity
- Cardiopulmonary involvement
- Mild-moderate mental retardation
- X-linked recessive
How does alphafetoprotein reach maternal serum
AFP reaches maternal serum:
- directly across placenta
- Indirectly from amniotic fluid across chorion & amnion
- and uptake by maternal vasculature in uterine decidua
- Levels change with gestation (lower in 2nd than 1st trimester)
- used in the quadruple test to screen for NTDs and downsyndrome
What does the quadriple test involve
screening 0involving
- Alpha-feto protein (high levels=bad)
- unconjugated estriol (low=bad)
- human chorionic gonadotrophin (VERYhigh= bad)
- inhibin A (high= bad)
What is the significance of PAPP-A
- used for screening; 12 week combined screening test
- low levels can be associated with downsyndrome
- Levels less than 0.5 =low
- hormone that is produced by the placenta in pregnancy
