Prenatal Genetics Flashcards
Specific segments of DNA that are required for the production of a functional product.
Gene
Structural units consisting of chromatin and DNA that transmit genetic material from parent to offspring
Chromosome
structure, number, and inheritance, in relation to medical genetics.
Approximately 1:160 live births results in a chromosome abnormality, while approximately 1:2 spontaneous miscarriages results from a chromosome abnormality.
Chromosome disorders account for a substantial subset of prenatal, pediatric and adult complications, including but not limited to miscarriage, stillbirth, birth defects, unusual facial characteristics and other dysmorphic features, cognitive deficiencies, and tumor development.
Clinical Cytogenetics
•___= Normal number of chromosomes
_____ = Most human somatic (body) cells carry two copies of each chromosome.
23 chromosomes x 2 = 46 chromosomes (2n = 46)
Euploid
Diploid
Reproductive cells carry half of the chromosomes within a somatic cell: 46 chromosomes / 2 = 23 chromosomes (n = 23)
Haploid
• A numerical deviation involving an exact multiple of the haploid number (n = 23).
- Triploid (69 chromosomes)
- Tetraploid (92 chromosomes)
Polyploid
• A numerical deviation not involving an exact multiple of the haploid
number (n = 23).
• Trisomy 18 (47 chromosomes) • Monosomy (45 chromosomes)
Aneuploid
(3n) is a euploid complement of the standard diploid (2n) chromosome number, in which there is a third extra set of chromosomes equally 69 chromosomes instead of 46.
*occurs in 1-3% of pregnancies; however, it is lethal in virtually all cases. The prognosis depends on the parent of origin contributing to the extra set of chromosomes.
Triploidy
extra set of chromosomes of MATERNAL origin
small placenta
often spontaenous abort
• Digynic triploidy
Extra set of paternal chromosomes, type of triploidy
enlarged placenta while the fetus often is not growth restricted. This is referred to as a partial hydatidiform mole.
Diandric pregnancy
Risk associated with diandric triploidy
the risk to the fetus, women with partial molar pregnancies are at risk for severe early onset preeclampsia, hyperthyroidism, multiple theca lutein cysts, and gestational trophoblastic disease.
risk factors of aneuploidy
- The risk for aneuploidy increases with maternal age.
- Defined as 35 years of age or older at the estimated date of
delivery (EDD) in a singleton pregnancy.
- The risk of Down syndrome at live birth is 1:385 for a woman who is 35 at the EDD, while the risk for any major aneuploidy at live birth is 1:204 at this age.
- In a twin pregnancy, advanced maternal age is defined as 33 years of age or older at the EDD. This risk of Down syndrome is 1:347 for at least one twin, while the risk for any major chromosome abnormality is 1:176 at the EDD.
• Cognitive deficiencies, vision problems, hearing loss, thyroid dysfunction, increased risk for early onset dementia or cancer, and congenital anomalies (i.e. heart malformations, gastrointestinal abnormalities). The prevalence is 1:800 live births.
Trisomy 21 (Down syndrome)
Limited to severe psychomotor delays, growth restriction, microcephaly, micrognathia, distinctive hand/finger posturing and rocker bottom feet, and congenital anomalies (i.e. heart malformations, omphalocele, oral clefting, clubfoot). The prevalence is 1:3,000 live births
Trisomy 18 (Edwards syndrome)
• Limited to severe psychomotor delays, microphthalmia, polydactyly, and congenital anomalies (i.e. oral clefting, holoprosencephaly, brain abnormalities, heart malformations, diaphragmatic hernia). The prevalence is 1:10,000 live births.
Trisomy 13 (Patau syndrome)
Growth retardation, infertility with only 5% of patients experiencing spontaneous menstruation, hearing loss, possible cognitive disabilities, and congenital anomalies (i.e. heart malformations, cystic hygroma, horseshoe kidney and other renal abnormalities). The prevalence is 1:2,500 live born females.
Monosomy X (Turner syndrome)
Tall/lean build, infertility, slightly delayed motor and language milestones, possible cognitive disabilities, increased risk to develop extragonadal germ cell tumors, male breast cancer, autoimmune disorders. The prevalence is 1:500-1,000 live born males.
XXY syndrome (Klinefelter syndrome)
Chromosome material is exchanged equally (balanced) or unequally (unbalanced).
Reciprocal translocation
The short arms (p) of two chromosomes are lost and the remaining long arms (q) are joined.
Robertsonian translocation
A balanced translocation involves the exchange of chromosome segments, in which these chromosome segments are not deleted (lost) or duplicated (gained) and carriers have a_____ phenotype, but they have on average a _____ risk of passing on an unbalanced chromosome complement to offspring.
normal
5-10%
• An unbalanced translocation involves chromosome segments that are deleted or duplicated, carriers have an_____ phenotype including birth defects, unusual facial characteristics, hearing/vision loss, mental retardation.
abnormal
the loss of a segment of chromosome, which may include any chromosome and any length/size.
occur in approximately 1:7,000 live births.
Deletion
Individuals with a deletion have a chromosomal imbalance (partial monosomy) and therefore the phenotype generally results from haploinsufficiency =
, or the inability of a single copy of a genetic unit to perform the function of two copies.
A duplication is the gain of a segment of chromosome, which may include any chromosome and any length/size: are much more uncommon as compared to deletions.
Similarly to deletions, individuals with a duplication have
a chromosomal imbalance (partial trisomy).
First Trimester Screen
• A routine test for risk assessment of
fetal Down syndrome, trisomy 13, and trisomy 18. Indicated for all pregnant patients regardless of fetal aneuploidy risk.
Cell-free fetal (cff) DNA / Non-invasive Prenatal Screening (NIPS)
• _______ test for risk assessment of fetal Down syndrome, trisomy 13, trisomy 18, and sex chromosome abnormalities. Indicated for high-risk pregnant patients.
A non-routine
High-risk factors include advanced maternal age, previous pregnancy or positive family history of common aneuploidy, abnormal fetal ultrasound or screening blood test suggestive of a chromosome abnormality:
what test could they get?
Cell-free fetal (cff) DNA / Non-invasive Prenatal Screening (NIPS)
• A non-routine test for risk assessment of fetal Down syndrome, trisomy 13, trisomy 18, and sex chromosome abnormalities
A routine test for risk assessment of fetal Down syndrome, Trisomy 18, neural tube defects (spina bifida, anencephaly) and abdominal wall defects (gastroschisis). Indicated for all pregnant patients regardless of fetal aneuploidy risk.
Maternal Serum Quad Screen
Tested in Maternal Serum Quad Screen
• A routine test for risk assessment of fetal Down syndrome, Trisomy 18, neural tube defects (spina bifida, anencephaly) and abdominal wall defects (gastroschisis)
Chorionic villus samplin, amniocetesis adn cordocentesis or percutaneous umbilical blood sample are all examples of:
Prental diagnostic testing
• Prenatal diagnosis of fetal aneuploidy, other chromosome, abnormalities (i.e. deletion), and single gene disorders. Does not screen for neural tube defects.
Indicated for increased fetal aneuploidy risk
Chorionic Villus Sampling (CVS)
A sample of placental chorionic villi is obtained by trans-abdominal/cervical biopsy.
Female pregnant and had prior birth with Trisomy 18. What testing can she do?
Chorionic Villus Sampling (CVS) ; ndicated for increased fetal aneuploidy risk
• Prenatal diagnosis of fetal aneuploidy, other chromosomal abnormalities, single gene disorders, and abnormal biochemical levels. Amniotic fluid AFP analysis and acetyl cholinesterase (AChE) for detection of open neural tube defects and abdominal wall defects.
Indicated for pregnancies with increased risk
Amniocentisis
How do you perform amniocentisis, who should get it?
sample of amniotic fluid is obtained via trans-abdominal biopsy, and floating fetal cells are used for culture, chromosomal and DNA analysis.
for pregnancies with increased risk
• Used as follow-up when amniocentesis culture fails or yields ambiguous results, or when biochemical tests of fetal plasma or blood cells, or infection need to be confirmed.
Cordocentesis/Percutaneous Umbilical Blood Sampling (PUBS
How id PUBS performed?
• A sample of fetal blood directly from umbilical vein with ultrasound guidance or infusion of blood products.
Alcohol effect on fetus
- Maternal consumption of 8-10 alcoholic drinks or more per day most often has been reported among infants with fetal alcohol syndrome; however, effects also have been reported with lower maternal consumption quantities.
- Alcohol generally affects the cellular pathways primarily related to the development of the central nervous system and craniofacial structures.
an oral medication for treatment of severe acne, has been found to be associated with an increased risk for congenital anomalies, including CNS abnormalities, craniofacial abnormalities, and heart defects, in addition to cognitive deficiencies.
Retinoic Acid (Isotretinoin)
• Maternal use of isotretinoin (Accutane),
Retinoic acid is a natural component in ____; however, excess levels are unlikely, as to whether the ingested dose is enough to cause suppression of bone growth and staining of the teeth in the nursing infant. Caution still is recommended
breast milk
oral anticonvulsant medication, associated with an increased risk for congenital anomalies, including neural tube defects, oral clefts, craniofacial abnormalities, heart defects, in addition to cognitive deficiencies.
Maternal use of valproic acid, an anticonvulsant
* should still breast feed
SSRI and birth defects
not associated with increased genetic defects
–> babies may have withdraw when mom takes them during 3rd trimester
are excreated into breastmilk but still shuld breast feed
lso known as complex inheritance, is the type of non-mendelian inheritance involving a trait or phenotype that results from an unclear combination of genetic and environmental factors.
• Affected individuals may cluster or aggregate in families because relatives are more likely to share predisposing alleles. Greater concordance for traits or disease within families is expected among close relatives as opposed to distant relatives.
Multifactorial Inheritance
Multifactorial Inheritance
• The population-based incidence of a trait or disease and the degree of relationship within a family of affected and non-affected individuals often are
the only sources available for risk assessment.
• Multifactorial traits and diseases include
pyloric stenosis, spina bifida, oral clefts, diabetes mellitus, mental illness.
If one parent is affected, each child will be a carrier.
If one parent is a carrier, there is a 50% chance for a child to be a carrier.
If both parents are carriers, there is a 25% chance for a child to be affected, a 50% chance for the child to be a carrier, and a 25% chance for a child to be unaffected in every pregnancy.
Autosomal Recessive Inheritance
mild to profound mental retardation
behavior abnormalities/autistic tendencies
macrocephaly and other subtle facial characteristics
increased risk for premature ovarian failure among females
increased risk for adult-onset cerebellar ataxia/intention tremors.
Fragile X syndrome
Fragile X syndrome is caused by
abnormal repeats of DNA code within the X chromosome and therefore it is inherited in an X-linked pattern.
- An affected father has a 50% chance to pass on the variant allele in every pregnancy.
- If the affected father has a has a daughter, she has a 100% chance to be a carrier. If the affected father has a son, he has a 100% chance to be normal.
- A carrier mother has a 50% chance to pass on the variant allele in every pregnancy resulting in carrier daughters or affected sons.
X-Linked Inheritance
