Week 2 Borch Flashcards
What is the use of oligo arrays?
Can probe down to the level of resolution of a SNP (ie SNP array, extremely high density oligo array). Can use relative strength of signal to detect copy number. Oligo array – provides copy number SNP array (ie, extremely high density oligo array) – provides code info
Differentiate Analytical Validity, Clinical Validity, and Clinical Utility
Analytical validity – accuracy, reliability
Clinical validity – degree of true association between having mutation and increased risk relative to population
Clinical Utility – the ability of the test results to improve patient outcomes
Minor malformation
<4% population, but does not require intervention
Major malformation
has significant medical consequences, requires intervention
Malformation
did not form correctly
Deformation
formed correctly, but outside forces altered shape, etc
Disruption
formed correctly, but outside forces destroyed it partially or completely (ie amniotic bands)
Malformation syndrome
group that “goes together,” due to single underlying cause
Malformation sequence
single malformed structure causing one or more secondary malformations as a consequence
Omphaloceole
abdominal wall malformation causing extrusion of viscera into peritoneum covered sack associated with ombilicus
Gastroschisis
abdominal wall malformation causing extrusion of viscera without any membranous covering, without association with ombilicus
Triploidy
Microsomia (small body, head is normal size)
Syndactyly of 3rd and 4th digits
Cystic placenta
Trisomy 21
Face/head: upslanting palpebral fissures, epicanthal folds, hyperglossia (big tongue), flat occiput (brachycephaly), brushfield spots in eyes
Body: redundant neck skin
Hands: single palmar creases, pinky clinodactyly
General: Hypotonia
What is the leading cause of death in Down Syndrome babies <1 y/o?
Cardiac Complications
Trisomy 18
Face/Head – prominent occiput, micrognathia
Extremities – overlapping digits, rocker bottom feet
Body – omphaloceole is common
Trisomy 13
Face/Head: scalp defects, micropthalmia (and/or hypotelorism), cleft palate defects, holopresencephaly
Other: polydactyly, rockerbottom feet
Turner Syndrome
Single X chromosome
General: Small stature, gonadal dysgenesis
Body: Neck webbing, shield chest
Cardiac and renal abnormalities (horseshoe kidney)
Intellectual impairment NOT a prominent feature
Klinefelter Syndrome
XXY phenotype
Phenotype is general “feminization” of the male form
Tall, gynecomastia (growth of breast tissue), microorchidism (small testes)
Intellectual impairment more common
XYY
Phenotype is variant of normal; maybe taller
Aggressive/antisocial behavioral tendencies???
XXX
Phenotypic variant of normal; taller, with some fertility problems
Possibly some learning/intellectual problems
Cri du Chat
5p deletion Shrill cry Microcephaly Downslanting palpebral fissures Hypertelorism Mental retardation
Wolf-Hirshorn
4p deletion Frontal bossing (Roman Helmet) Micrognathia Hypospadius Cardiac defects Extreme MR (Wolf-Hirshorn – I think of a Germanic warrior, covered in a Wolf pelt with a Horned Viking helmet fighting a Roman Centurian (frontal bossing))
Prader-Willi
Loss of expression of PATERNAL allele of ch. 15 (parental imprinting)
Neonatal hypotonia
Propensity to morbid obesity
Mental retardation
Small gonads/genitals
(Phenotype ~ Little Billy from the Gary Larson cartoons)
Angelman
Loss of expression of MATERNAL allele of ch. 15 (parental imprinting)
Happy puppet on strings
Seizures and jerky ataxic movements
Severe MR
Williams Syndrome
7q deletion
Uncanny musical propensity (at expense of diminished mathematical/spatial ability)
“Elfin” facies
Cocktail party personality
Describe the typical findings in the 22q deletion syndromes.
CATCH 22
Cardiac defects Abnormal Facies Thymic Aplasia Cleft Lip Hypocalcemia
Why? Because 22q is important for pharyngeal arch development, note these structures are all from pharyngeal arches.
DiGeorge Syndrome
22q deletion
CATCH 22 symptoms
Small at birth
Velocardiofacial Syndrome
22q deletion
CATCH 22 symptoms
More common to have cleft palate abnormalities
Broad nose
Miller-Dieker
17p deletion
Thin upper lip
Lissencephaly (poor brain formation – no gyri and sulci, just smooth cortex)
Severe MR
What is the big disadvantage of a Microarray analysis?
Balanced translocations are NOT detected
In general, when do we suggest diagnostic testing?
When the risk of significant abnormalities exceeds the risk of the procedure. Note: this may not be 35 y/o.
Give the typical malformations/defects seen in the following maternal health conditions:
Diabetes Mellitus
Seizure disorders
Congenital Adrenal Hyperplasia
DM ONTDs, Sacral agenesis
Seizure disorders ONTDs (not accounted for solely by meds)
Congenital Adrenal Hyperplasia virilization
First Trimester screening tests for Down Syndrome?
Nuchal translucency US
Beta HCG, PAPP-A
Second Trimester screening tests for Down syndrome?
Quad screen: AFP Beta HCG Unconjugated Estriol 3 Inhibin A (note: these will all be decreased in other trisomies)
What is the role of cell-free fetal DNA in testing?
Useful, but not yet gold standard.
On a test, go with the gold standard (1st and 2nd trimester screenings)
