Karyotypic Abnormalities Flashcards
How many cells does a karyotype typically analyze?
so it looks at living, dividing cells that are stopped in the middle of cell division
looks at chromo of 20 cells, deeply analyzing 5
What is the range for good band counts? poor band counts?
good = 550-650
poor = 350-450
(can dep on cell type, so like amniocytes will have weaker band count)
What ype of FISH can use cells that are not dividing?
Interphase FISH
(3-5 day turnaround time)
When is chromosomal disorder our first thought that comes to mind?
when you see a disorder that involved multiple unrelated systems + mult congenital anomalies
What is the suspected critical region os chr21?
21q21.22
but multiple regions are suspected; this is not quite known yet
What are 3 major anomalies in Tri21 taht we want to look for right away?
- heart defect
- duodenal atresia
- Hirshsprung disease
What are some abnormal labs taht are associated with Tri21?
- transient myelopoiesis (20-30% risk leukemia)
- hypothyroidism
What are common cardiac findings in Tri21?
50% have heart anomalies:
40% AVSD
32% VSD
10% ASD
TOF 6%
Describe duodenal atresia and prevalence in Tri21
this is when the duodenum (C curve) has a blockage or discontinuity so that nothing can move through it –> baby cannot eat and stomach blows up w gas –> double bubble
25-40% kids w duo atresia have Tri21
5% kids w Tri21 have duo atresia
Describe Hirschsprung and its prevalence in Tri21
the ganglion cells (resp for squeezing + forward movement of stool) do not migrate to the rectum —> means absense of ganglion cells –> that area is small and v tight
leads to vomit + repeat –> baby needs surgical repair
this is V dangerous to send a child home w this
- present in 2% Tri21
- 12% w Hirsch have Tri21
What are some major physical findings in Tri21?
low tone (noticable right away)
microcephaly
brachycephaly
upslanting palpebral fissures
epicanthal folds
flat nasal bridge
tongue thrusting
small cupped ears
redundant nuchal skin
single palmar crease + clinodactyly 5th finger
sandal gap
What are some ENT + Vision problems we see in Tri21?
82% w frequent ear infections w conductive hearing loss (due to abnorm of eustachian tube bc absent nasal bone does not allow that pressure to equalize between the nose + the ear)
56% visual problems, usu near sighted
What are some autoimmune findings in Tri21?
risk of autoimmune disorders w thyroid + Celiac (bc have problems w absorption)
If patients w Tri21 are particularly active, what is something we want to look for?
they can have Atlanto-axial instability (base of skull to spine), so want to look at flexion and extension x-rays to make sure neck is ok
What is the avg age of development for Tri21?
2nd grader
Why is premature Alzheimer’s in adults common in Tri21?
the precursor protein in on Tri 21 (APP (amyloid precursor protein))
What are the fertility risks assoc w Tri21?
males = usu infertile
females = subfertile (15030% fertile)
What is risk for someone w Tri21 to have an affected child?
empirical data says 35-50%
What is approximate risk for woman age 40 to have child w Tri21?
1/100
What are the most common to least common causes for Tri21?
95% nondisjunction
- 90% maternal, 10% paternal
- 77% Mei I, 23% Mei II
- Mei I - usu maternal
- Mei II - usu paternal
4% Rob translocation
1% mosaicism
<1% partial dup
What are the recurrence risks of Tri21 w respect to the genetic cause?
- Nondisjunction –> ~1-4% if <30y (then age related risk for >30y)
- Rob trans –> empirically derived:
— t(14:21) 10-15% maternal, <5% paternal
—21q21a isochromosome: 100%
Causes of Tri18?
- 94% maternal nondisjunction (usu Mei II) + association w mat age
- 5% mosaicism
- ~1% transloc or partial dup
What is the general prognosis for Tri18?
50% died w/in 1w birth
90% die by 1y (even w intervention) –> usu bc heart defect, primary apnea (stop breathing)
if they survive past 1y, then they are more likely to live longer
What are common physical findings in Tri18?
remember that everything is v small
- char craniofacial features
- overriding fingers
- nail hypoplasia
- short hallux
- rocker bottom feet
- short sternum
- prominent occiput
What % of babies w Tri18 die in labor?
38%
also, 1/3 = premature
What is the most common major congenital anomaly we see in Tri18?
90% heart defects (VSD, mult valve anomalies)
What are major anomalies we see in Tri18 when thinking of Cardiac, Pulm, Opthalm, and ENT?
- heart defects
- respiratory problems (laryngomalacia, trachoebronchomalacia, apnea, pulm HTN)
- opthalmology (10% cataract, corneal opacities, photophobia)
- ENT (mod-severe sensorineural hearing loss bc v small ears)
What are major anomalies we see in Tri18 when thinking of limbs, skeletal, renal, CNS?
- Limb anom (5-10%, radial aplasia, club foot)
- Skeletal (scoliosis - more when older)
- Renal (2/3 w horseshoe kidney, UTI more common)
- CNS (5% brain anom; 25-50% seizures)
Also - inc risk for neoplasia: Wilms tumor (1% risk), hepatoblastoma
What is the avg age for Tri18 developmentally?
older kids function at 6-8mo
What are some speech + motor skills that are lacking in Tri18?
most have no expressive language
most cannot walk indep
CAN recognize fam + smile at them
older kids can maybe understand words, crawl, follow command, interact a bit w others
Can parents always opt for surgical intervention for Tri18?
- dep on institution
- some will not provide surg intervention, some will for VSD for ex
- want to respect parents wishes + also being realistic
Why do those w Tri18 need an abdominal US every 6 months?
- want to check for renal malformation + Wilms tumor + hepatoblastoma
3rd most common trisomy?
Tri13 (Patau syndrome)
What are 2 big features that you want to think about when thinking of Tri13?
holoprosencephaly
cutis aplasia (think of that region on scalp that has no skin closure)
What are other main physical features of Tri13 other than holoprosencephaly + cutis aplasia?
- polydactyly
- renal anomalies
- eye anomalies (anophthalmia, microphthalmia)
What are som congenital anom assoc w Tri13?
CNS: holoprosencephaly, Dandy Walker (cerebellum)
Heart: VSD, ASD, TOF, transposition of the great arteries
GU: polycystic kidneys, uterine agenesis
What is the prognosis for Tri13?
- 50% die w/in 1month
- 90% die w/in 1year (recent studies say maybe survival of 20%)
What are genetic causes of Tri13?
91% nondisjunction, usu Mei I
What are 3 prenatal indications for Turner syndrome?
hydrops, cystic hygroma, heart defect
What are some findings that might present in childhood/puberty to make the dx of Turner syndrome?
childhood
- isolated short stature
puberty
- primary amenorrhea
- lack of secondary sex char
also, hypothyroidism
What are some birth anomalies associated with Turner syndrome?
- webbed neck
- downslanting eyes
- low set ears, posteriorly rotated
- wide chest (w widely spacednipples)
- puffy hands and feet (edema)
- hyperconvex nails
What explains the short stature in Turner syndrome?
SHOX deficiency
- can also see Madelung deformity (radius shortened w curvature of the arm)
of note, can be responsive to growth hormone bc can overcome the signaling pathway
What explains the amenorrhea in Turner syndrome?
streak gonads –> since they are resp for providing estrogen for secondary sex devel
subfertility to infertility = typical
POF
Why might we see weight gain in Turner syndrome?
if they have hypothyroidism, then there may be poor metabolism in the muscles
What are common endocrine disorders associated with Turner syndrome?
95-100% w growth failure + red adult ht
90-95% w hypergonadotropic hypogonadism (gonads not resp well to the gonadotropins (FHS, LH) –> then they tell ovaries to release hormones, which cannot happen in this case)
15-50% glucose intolerance
Type I diabetes
10% Type II diabetes
What are some main features of Klinefelter syndrome (47,XXY)?
hypergonadotropic hypogonadism (pituitary is great, then testes do not respond)
male factor infertility
tall stature
low tone
difficulties in school (w ELA)
trouble regulating emotions
Why do those w Klinefelter syndrome (47,XXY) have tall stature?
they have an extra copy of SHOX
How are Klinefelter and Triple X simialr in presentation?
- speech dev delays
- motor dev delays
- mild reduction in IQ, usu more so bc of immaturity
- tall stature
- low tone
What trisomy had been historically ties to inc risk of imprisonment?
XYY Jacob’s syndrome
those were biased though, we know now that they usu have inc risk of autism, ADHD, emotional control
What causes Wolf-Hirschhorn?
4p-
55% w terminal del
Ring 4 chromo
4p- mosaicism
unbalanced transloc
What was a historical way to describe Wolf-Hirschhorn?
Greek warrior helmet facies
What are the most common findings in Wolf-Hirschhorn? (>75%)
- IUGR/postnatal growth def
- ID
- hypotonia
- muscle hypertrophy (become small and skinny)
- seizures
- feeding difficulties
- abnormal ears
What are the less common findings in Wolf-Hirschhorn? (<75%)
50-75%:
- EEG abnorm
- skeletal anom
- craniofacial asymm
- abnormal teething
- ptosis
- antibody def
25-50%:
- heart defects
- hearing defects
- eye/optic nerve defects (like coloboma)
- cleft/lip palate
- structural brain anom
- GU tract defects
- renal anom
What causes cri du chat?
5p-
80-90% paternal in origin
10-15% due to unbal parental transloc
80-90% term del
3-5% bc interstitial del
uncommon=mosaicism, inversions, ring chromo
What are the main findings associated with cri du chat?
laryngeal malformation resulting in high pitched monotone cry (hear meowing sound in nursery)
dev delay/ID
craniofacial findings
other congen anom
What are some facial features associated with cri du chat?
- round face
- prominent metopic bossing
- broad nasal bridge, lateral downslanting palpebral fissures
- hypertelorism
- epicanthal folds
- strabismus divergent/convergent
- short philtrum
- down turned corners of mouth
- low-set ears
of note, high arched palate is a big one
dysm feat are not a dead giveaway for this one
What are some medical features associated with cri du chat?
35% congenital heart disease
30% abnormal MRI
- absense corpus callosum
- small cerebellum
18% renal abnorm
- small kidneys, ectopic
gential abnorm
- cryptorchidism
- inguinal hernia
dev delay
- mod to sev (dep on the del)
What is the cause of cat-eye syndrome?
isodicentric marker 22q11 –> tetrasomy
q region gets dup around centromere
What are main findings in cat-eye syndrome?
- coloboma = “cat eye” (due to the defect in dev of the optic nerve)
- preauricular anom (pits, tags)
- hearing loss
- heart defect
- renal anom
- anal atresia
- ID (mild)
What are the causes of Turner syndrome?
40-50% = 45,X
15-25% = mosaicism 45,X/46,XX
20% = isochromosome
ring X = present in a few women
10-12% women have some Y material
(~3% present 45,X/46,XY)
