Chromosomal Defects Flashcards
What do ~20% of infant deaths in US results from?
Birth defects
When is the maternal serum screen (MSS) done?
15-20 wks gestation
What three malformations does MSS look for?
Trisomy 21
Trisomy 18
Neural tube defects
What levels of AFP, uE2 and hCG show in Trisomy 21?
AFP - low
uE2 - low
hCG - high
What levels of AFP, uE2 and hCG show in Trisomy 18?
Low in all
What levels of AFP, uE2 and hCG show in Neural Tube Defects?
AFP - high
uE2 - normal
hCG - normal
Define anomaly.
A structural defect of any type
Define malformation.
Intrinsic; genetic
Define deformation.
Extrinsic; mechanical
Define disruption.
Extrinsic; teratogen exposure
Define syndrome.
Multiple anomalies that occur independently, but are cause by a single defect
Define sequence.
When a structural or mechanical factor leads to multiple secondary effects
What are some general characteristics of multifactorial disorders?
Disorders that tend to run in families
No single gene or chromosomal abnormality is responsible
Usually a combination of genetics & environmental factors required for phenotypic expression
Do not follow Mendelian patterns of inheritance
What are some general characteristics of whole chromosome disorders?
Usually incompatible with life Rarely reproduce Most directly linked to maternal age May occur in autosomes or sex chromosomes Detectable via karyotype analysis
What are some examples of Multifactorial disorders?
Coronary artery disease IDDM Hypertension Some forms of cancer Some developemental defects including: Congenital heart defects Spina bifida Anencephaly Cleft palate
What is XXX?
A common abnormal karyotype also known as super female.
What is XO?
Turner syndrome
The only recognized monosomy
What is XXY?
Klinefelter syndrome
What is XYY?
A common abnormal karyotype also known as super male.
What are some symptoms of Klinfelter Syndrome?
47, XXY 1st recognized sex chromosome abnormality Tall Low IQ Infertile Hypogonadism Gynecomastia
What are some symptoms of Turner Syndrome, the only true monosomy?
45, XO Short Infertile Normal IQ Webbed neck Broad chest/wide set nipples 25% mosaics
What is fragile X syndrome?
An X-linked disorder that about 1/1500 males get
What is fragile X syndrome characterized by?
Mild connective tissue dysplasia
Macro-orchidism
Dental crowding
What is fragile X syndrome caused by?
By GCC repeats in 5’ UTR of FMR1 gene
What are the normal, submutation and Fragile X values for the GCC repeats?
Normal = 29 repeats
Submutation = 29-230 repeats
Fragile X = >230
What gene is silenced in fragile X syndrome and how?
FMR1 silenced via methylation
What is trisomy 21, 18 and 13?
21 = Down syndrome 18 = Edward syndrome 13 = Patau syndrome
What are the clinical features of trisomy 21?
Mental retardation Epicanthic folds Hypotonia Simian creases Short stature Furrowed tongue Heart defects Predisposed for leukemia Brush field spots on iris Gap b/w 1st and 2nd toes Neurofibrillary tangles Duodenal obstruction
What is the incidence of trisomy 18?
1:8000
What are the clinical features of trisomy 18?
Mental retardation Rocker-bottom feet Malformed ears Hypoplastic nails Rarely survive past infancy
What is the incidence of trisomy 13?
1:25000
What are the clinical features of trisomy 13?
Lethal by 6 mo
Severe CNS malformations
Often cleft lip/cleft palate
70% have holoprosencephaly
What are the features of Cri du chat syndrome?
5p deletion Microcephaly Micrognathia Hypertelorism Malformed ears Severe retardation
What are Robertsonian Translocations?
Translocations between 2 acrocentric chromosomes
What translocation is associated with a familial form of Down Syndrome?
14q;21q
What are teratogens?
Drugs, chemicals & infectious agents that may adversely affect fetal development
What are important factors that affect the outcome of teratogen exposure?
Time of exposure
Dosage
Fetal/Maternal genotype
What are some examples of drugs/chemicals that act as teratogens?
Thalidomide
Retinoic acid (Accutane)
Alcohol
Hydantoin (Dilatin)
What do ACE inhibitors do as teratogens and at what point do they cause these problems in pregnancy?
kidney defects; in the 2nd and 3rd trimester
How bad are antineoplastic agents as teratogens?
Severe
What type of effects does mercury have as a teratogen?
Neurotoxin with cerebral-palsy like syndrome
What is an example of a lack of a morphogen?
Folate which is critical for neural tube development
What does a maternal deficiency in Vitamin A (Retinoid Acid) lead to?
Small eyes (microphthalmia)
Cleft palate/lip
Cardiovascular & urogenital anomalies
Malformed limbs
What are the clinical features of Fetal Alcohol Syndrome?
Major cause of mental retardation Skeletal defects Growth retardation Heart Defects Smooth philtrum 1 in 6 have cleft palate
What are the clinical features of Fetal Hydantoin Syndrome?
Craniofacial anomalies
Growth retardation
Mental retardation
Limb defects
What is the degree of severity linked to in fetal hydantoin syndrome?
Low activity form of epoxide hydrolase in mother
What are the teratogenic infections?
TORCH Toxoplasmosis Other: HIV, Syphilis, VZV Rubella CMV HSV
What symptoms may come from maternal diabetes mellitus?
Cardiovascular defects
CNS defects
What symptoms may come from maternal phenylketonuria?
Microcephaly
Congenital heart defects
Retardation
