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)