Congenital Anomalies & Birth Defects; Practice Quiz
Phases of birth defects: fetal period
Teratogen exposure produce structural/functional abnormalities particulary of brain & eyes
Phases of birth defects: 3-14 wks organogenetic period
Teratogenic exposure disrupt organogenesis, causing major birth defects
Phases of birth defects: 0-2 weeks of development
Teratogenic exposure kills the embryo (aborted) or have no effects
Principles of embryology, pathology and toxicology to understand & classify developmental defects of malformed embryos and fetuses
Teratology
In the 1950s what drug was given to pregnant women to alleviate morning sickness?
Thalidomide
Major defects occur in early embryos (___%); less in neonates (___%)
- 15% - 3%
Neonates show less defects ___%, but by 5-year the defects are more apparent __%. Later in life (__%), e.g., during surgery, dissection, autopsy, accidents etc. reveal the defects
- 3% - 8% - 2%
Effect of teratogens depend on:
- Critical periods of development - Dose of the drug or chemical - Genetic background of the embryo
47, XXX Sex? Characteristics?
- Female - normal in appearance; usually fertile; 15% to 25% are mildly mentally deficient
Congenital Rubella Syndrome: Triad
- Head: microcephaly - Eye: anophthalmia/microphthalmia (eyeballs missing/small) - Heart: PDA (patent ductus arteriosis); VSD (ventricular septal defect)
Birth defects caused from smoking
- IUGR (<2000 g babies) - chronic fetal hypoxia - carboxyhemoglobin--> smaller brain volumes
Consequences of birth defects in week 3-8
- Most susceptible period; Major birth defects: amelia (absence of limbs), neural tube defects, spina bifida cystica - malformation of embryo may occur (brain & heart defects)
Congenital rubella syndrome: eye anomalies
- cataracts - primary congenital glaucoma (high pressure in eye damages optic nerve) - strabismus (cross-eyed) - nystagmus (dancing eyes) - microphthalmia - iris dysplasia
Down syndrome physical appearances
- flat facial profile and an upward slant to eye - short neck - abnormally shaped ears - single, deep transverse crease on the palm of hand
Where is SHH expressed?
- notochord - neural tube floor plate - brain - developing limbs - gut
Turner syndrome features
- short, webbed neck and prominent ears - lymphedema of hands & feet - no sexual maturation - broad chest (widely spaced nipples)
Trisomy 13 is also known as
Patau syndrome; 1:12000 incidence; usually die early in infancy
Sonic Hedgehog Pathway (SHH)
Perturbations in SHH-PTCH-GLI signaling pathway lead to several birth defects
Neural tube defect is an example of which type of birth defect?
congenital abnormaility
Mutant gene defect assoc with excessive androgens; causes masculinized external genitalia
congenital suprarenal (adrenal) hyperplasia
A partial terminal deletion from the short arm of chromosome 5 causes
cri du chat syndrome
Birth defects caused by streptomycin
deafness
Birth defects caused by lithium
defects in the heart and great vessels
Trisomy 21 is also known as
down syndrome; represent 10%-15% of institutionalized individuals with severe mental retardation; 1:800 incidence
Consequences of birth defects in the first 2 wks of development
embryonic death & spontaneous abortion
Birth defects caused by tetracycline
enamel hypoplasia, tooth defects, short bones
Result of nondisjunction
extra chromosomal pair or chromatids in one daughter cell and missing chromosome in other daughter cell
Birth defects caused by rubella virus
eye defects (glaucoma & cataracts), deafness, & cardiac defects
Abnormalities in 3-4 gene loci can cause
facial clefts or CLP (cleft-lip-palate)
Fetal toxoplasmosis is an example of which type of birth defect?
fetal disease
Sporadic/ inherited SHH gene mutations leads to
holoprosencephaly
Cri du chat diagnosis
infants have weak cat-like cry, microcephaly, severe mental deficiency, congenital heart disease
Birth defects caused by thalidomide
limb, cardiac and kidney defects
Fragile x syndrome characteristics
long face, prominent ears, learning disability, strabismus
Environmental agents (teratogens) cause developmental defects (7-10%) in the fetus after
maternal exposure
Fragile X syndrome: expansion to >55-200 CGG repeats gets _____ and the gene is silenced
methylated
Mutant gene defect in which infants are grossly mentally deficient bc brain is underdeveloped; 25,000 infants diagnosed annually
microcephaly neurodevelopment disorder
Birth defects caused by alcohol consumption
microcephaly, fetal syndrome or FASD, heart defects
Birth defects can be classified into what 5 categories?
Structural, Functional, Metabolic, Behavioral, Hereditary
PDA and VSD result in
mixing of blood and cyanosis
Birth defects caused by varicella virus (chicken pox, shingles)
muscle atrophy, short limbs/digits, eye/brain damage
Failure of a chromosomal pair or two chromatids of a chromosome to disjoin during mitosis or meiosis
nondisjunction
Birth defects caused by multifactorial inheritence
nonsyndromic orofacial clefts
Birth defects caused by hepatitis b virus
preterm birth or fetal macrosomia (large baby; >4000g)
Holoprosencephaly: Failure of cleavage of:
prosencephalon (rostral neural tube) into right and left cerebral hemispheres, telencephalon and diencephalon, and olfactory bulbs and optic tracts
If two nonhomologous chromosomes exchange pieces, it is called a
reciprocal translocation
Thalidomide side effect
severe limb defect, cardiac & kidney defects
Birth defects caused by zika virus
severe microcephaly, retinal abnormalities, clubfoot
Achondroplasia characteristics
short stature, short limbs & fingers, bowed legs, large head, a prominent forehead, and a depressed nasal bridge
Fetal alcohol syndrome characteristics
thin upper lip, poorly formed philtrum (vertical groove on upper lip), short palpebral fissures (corners of eye), flat nasal bridge, short nose
Birth defects caused by toxoplasma gondii (endoparasite)
uncooked meat & cats --> infection --> microcephaly, microphthalmia and hydrocephaly
Common x-linked disorders (1:4000 in males) associated with mental impairment & Autism spectrum disorders (ASD) & Strabismus
Fragile x syndrome
Cystic fibrosis is an example of which type of birth defect?
Genetic disease
47, XYY Sex? Characteristics?
Normal in appearance, usually tall, and often exhibit aggressive behavior
Malfunctioning in mitosis or meiosis cause
chromosomal aberrations
Fragile X syndrome diagnosis
chromosome lesion at Xq27.3 and expansion of CGG nucleotide repeats in a specific region of the FMR1 (fragile x mental retardation 1) gene required for cognitive development
Birth defects caused by Warfarin
NASAL CARTILAGE DEFECTS, mental deficiency, optic nerve atrophy, microcephaly
Four clinically significant types of birth defects
1) malformation 2) disruption 3) deformation 4) dysplasia
Stages less sensitive to teratogens (minor functional defects/anomalies
Fetal period (week 9-38) - mental deficiency
Mutant genes causes approx what fraction of all birth defects?
1/3
The medical belief that baby's are protected in the womb by sterile environment changed in what year?
1941; Rubella virus infection in pregnant mothers cause German measles which lead to "congenital rubella syndrome"
Critical period for brain and heart development
3-16 weeks
___% of infants with down syndrome have translocation trisomies; extra chromosome is attached to another chromosome
3-4%
How many children worldwide have a serious birth defect?
8 million
A highly specialized cellular layer of theca folliculi produces the hormone estrogen. Which one of the following layer is this? A) Vascular theca interna B) Glandular theca externa C) Zona pellucida D) None of the above
A) Vascular theca interna
Which of the following embryonic week does the embryo show first spontaneous movements in the trunk and the limbs? A) Fourth week B) Sixth week C) Eight week D) Eighteenth week
B) Sixth week
Both copies of gene (homozygous mutations) are mutated for a phenotype. A parent (heterozygous defective gene) is a carrier with no phenotype.
Autosomal recessive disorder
At what fetal age the developing eyes turn from anterolateral to anterior position? A) 30-38 weeks B) 13-16 weeks C) 21-25 weeks D) 8-12 weeks
B) 13-16 weeks
Lack of gonadotropins in women can cause a unique pathological condition. Which of the following represents this condition? A) Mittelschmerz B) Anovulation C) Acute vaginal bleeding D) None of the above
B) Anovulation
Congenital Suprarenal Adrenal Hyperplasia causes which one of the following congenital abnormality? A) Short stature and short limbs B) Masculinized external genitalia in female C) Mental retardation D) Hypertelorism
B) Masculinized external genitalia in female
Early transvaginal ultrasonography can detect which of the following conditions? A) Downs Syndrome B) Spina Bifida C) Tubal pregnancies D) Polydactyly
C) Tubal pregnancies
Birth defects caused by high levels of ionizing radiation
CNS defects (brain & spinal cord) & eyes
Which of the following combination reflects the five extraembryonic structures formed by embryonic day 8? A) Amnion, Amniotic cavity, Hypoblast, Umbilical Vesicle, Connecting stalk B) Amnion, Amniotic cavity, Hypoblast, Umbilical Vesicle, Syncytiotrophoblast C) Syncytiotrophoblast, Amnion, Amniotic cavity, Hypoblast, Cytotrophoblast D) Amnion, Amniotic cavity, Chorionic Sac, Umbilical Vesicle, Connecting stalk
D) Amnion, Amniotic cavity, Chorionic Sac, Umbilical Vesicle, Connecting stalk
Spina bifida cystica is a congenital abnormality. It occurs due to which one of the following reasons? A) fetal alcohol syndrome B) The mother has consumed the sedative Thalidomide C) The mother is infected with Rubella Virus D) Neural tube fails to fuse in the 4th week of embryo development
D) Neural tube fails to fuse in the 4th week of embryo development
Multiple genes of variable expression hypothesis:
Dominant gene with high & low penetration defines the phenotype
Trisomy 18 is also known as
Edwards syndrome; 1:8000 incidence; usually die early in infancy
Birth defects caused by polychlorinated biphenyls (FISH)
IUGR and skin discoloration
Birth defects caused by cytomegalovirus
IUGR, microphthalmia, blindness, microcephaly, deafness & cardiac defects
Hypertelorism
Increased distance between orbits (seen in cri du chat)
47, XXY Sex? Characteristics?
Male; Klinefelter syndrome: small testes, hyalinization of seminferous tubules; aspermatogenesis; often tall with disproportionately long lower limbs. Intelligence of siblings is less than normal. Approx 40% of males have breast (gynecomastia)
Why is fragile x syndrome more severe in males?
Males only have one X chromosome; in females it is a milder disease since they have XX
Trisomy
Meiotic nondisjunction of autosomes; three chromosome copies in a chromosome pair
Autism is an example of which type of birth defect?
Mental disorders
Birth defects caused by methylmercury (FISH)
Minamata disease; symptoms of cerebral palsy
Condition in which two or more cell types contain different numbers of chromosomes (normal or abnormal), leading to a less severe phenotype, with normal IQ
Mosaicism
(T/F) Translocation does not necessarily cause abnormal development
True
45,XO due to chromosomal nondisjunction
Turner syndrome
Birth defects caused by oral contraceptives
VACTERL syndrome (vertebral, anal, cardiac, tracheal, esophageal, renal, and limb anomalies
Spina bifida cystica
Vertebral defect (neural tube fails to fuse at 4th week); causes a cleft in the lumbar region with a visible cystic mass on the back; nerve damage is permanent; paralysis of lower limbs
At which one of the following embryonic age are the primary ossification centers in the cranium and limbs established? a) 12 weeks b) 9 weeks c) 7 weeks d) 18 weeks
a) 12 weeks
Holoprosencephaly
abnormal CNS septation, facial clefting, single central incisor, hypotelorism, or a single cyclopic eye
Birth defects caused by lead
abortions, fetal defects, IUGR and functional/cognition deficits
Birth defects caused by cocaine
abortions, prematurity, IUGR, microcephaly, urogenital and neurologic abnormalities
G-to-A transition mutation in FGFR3 (fibroblast growth factor receptor 3) gene on chromosome 4p
achondroplasia
Which acellular glycoprotein layer surrounds the primary oocyte during oogenesis? a) antrum b) zona pellucida c) follicular cell layer d) corpus luteum
b) zona pellucida
Persons with reciprocal translocation but no phenotype; gametes have abnormal translocation chromosome
balanced translocation carriers
Leading cause of infant mortality
birth defects
Embryogenesis is regulated by multiple
cell-signaling cascades. (Therefore, aberrant cell-signaling leads to birth defects)