Genetics and prenatal diagnosis Flashcards
1) What is the most common trisomy in abortuses?
a) Tri 16
b) Tri 18
c) Tri 13
d) Tri 21
A. Trisomy 16 is the most common triploidy in abortuses. 45,XO is the most common aneuploidy in first trimester abortion. Trisomy 21 is the most common in liveborn fetuses.
2) Which is seen with holoprosencephaly and midline facial defects?
a) Tri 13
b) Tri 21
c) Tri 18
A. Trisomy 13 is characterized by holoprosencephaly and midline facial defects.
3) Triple screen test shows a normal AFP, normal hCG, and a low E3. What condition is this associated with?
a) Down syndrome
b) Ichthiosis
c) Triploidy
B. Ichthiosis. Very low or absent estriol levels suggest placental steroid sulfatase deficiency, Smtih-Lemli-Opitz, congenital adrenal hypoplasia, ACTH deficiency, hypothalamic corticotropin deficiency, and anencephaly. Placental steroid sulfatase deficiency is an X-linked recessive disorder – prevents removal of sulfate molecule from DHEAS, preventing conversion to estriol. Greater than 90% of cases present as X-linked congenital ichthyosis – treated with topical keratolytic agents. 5% of cases have deletion of contiguous genes causing mental retardation, Kallman syndrome, or chondrodysplasia punctata. Prenatal diagnosis with karyotype or FISH.
Smith-Lemli Opitz syndrome is autosomal recessive resulting from 3-beta-hydroxysteroid reductase deficiency, alters cholesterol levels. Characterized by low birth weight, failure to thrive, MR, microcephaly, ptosis, syndactyly, and typical facies.
4) What is the most common cause of CAH?
4) 21-hydroxylase deficiency accounts for 90-95% of congenital adrenal hyperplasia.
5) How do you treat fetus if the mother has CAH?
Dexamethasone to prevent virilization of female fetus. Mother requires cortisol replacement.
6) When do you start treatment if the mother has CAH?
a) Prepregnancy
b) 7-8 weeks
c) 18-20 weeks
d) 14-16 weeks
e) After the CVS
B. 7-8 weeks. Dexamethasone is administered in at risk pregnancy before the end of the 7th week of conception (9 weeks EGA) to prevent virilization and can be stopped after CVS confirms male fetus or unaffected.
7) What karyotype is suggestive of uniparental disomy?
a) Tri 13
b) Triploidy
A. Trisomy 13. Uniparental disomy occurs when a disomic (euploid) cell line contains 2 chromosomes inherited only from one parent. Examples are Prader-Willi, Angelman, and Beckwith-Wiedemann (chromosome 11). It also occurs from a trisomic rescue – i.e. you’ll see a trisomy 13 in CVS, the fetus tries to save itself by losing a chromosome 13 but loses the wrong one and gets a uniparental disomy. Triploidy occurs when there is an entire extra chromosome set, usually from paternal origin.
8) Which maternal karyotype has the highest risk of Down syndrome?
Although 21 q21q (translocation composed of 2 chromosome 21 long arms) accounts for only a few percent of Down syndrome, when a parent carries this translocation all of their gametes must either convey trisomy 21 or monosomy 21.
9) The incidence of a disease is 1/6400, what is the carrier rate?
a) 1/20
b) 1/40
c) 1/80
d) 1/160
e) 1/320
B. 1/40. If incidence of disease=1/6400, this represents q2. q=1/80. p+q=1, so p=79/80, which is approximately equal to 1. So 2pq, which represents carrier frequency, is 21/80 * 79/80 ~ 1/801=2/80=1/40.
10) What is the risk of cystic fibrosis if a first-degree relative has the disease and if the carrier rate is 1/25?
a) 1/150
b) 1/25
c) 1/100
d) 1/300
10) A. 1/150. Let’s assume the first degree relative is a sibling. Then the parent has a 2/3 chance of being a carrier (¼ will be normal, ½ will be a carrier, ¼ will be affected, but we know that this person is not affected, so that leaves only 3 options: 1/3 will be normal, 2/3 will be a carrier). The parent has ½ chance of passing on their CF gene. The other parent has a 1/25 chance of being a carrier (per the question) & ½ chance of passing that gene on: 2/3 * ½ * 1/25 * ½ = 1/150.
13) What is the most common finding on a term infant with Down syndrome?
a) Simian crease
b) Hypotonia
c) LBW<2500gms
B. Hypotonia. Hypotonia is almost always present in trisomy 21 infants. Simian crease is present in only 30% of infants. The mean birth weight is 2900g.
14) What syndrome has coarctation of the aorta?
a) Turners
b) Marfans
c) Tetrology of Fallot
Turner’s
15) What condition with cystic fibrosis carries a poor prognosis?
a) Cor pulmonale
b) Recurrent pneumonia
c) Pancreatitis
Cor pulmonale
16) Which fetal syndrome has absent radius, polyhydramnios, and hydronephrosis?
Thrombocytopenia absent radius (TAR) syndrome is characterized by bilateral absence of the radii with the presence of both thumbs and thrombocytopenia (<50 platelets/nL) that is generally transient. Thrombocytopenia may be congenital or may develop within the first few weeks to months of life; in general, thrombocytopenic episodes decrease with age. Cow’s milk allergy is common and can be associated with exacerbation of thrombocytopenia. Other anomalies of the skeleton (upper and lower limbs, ribs, and vertebrae), heart, and genitourinary system (renal anomalies and agenesis of uterus, cervix, and upper part of the vagina) can occur. The diagnosis of TAR syndrome is primarily clinical: the combination of thrombocytopenia and absent radius with presence of thumbs suggests the diagnosis. In addition, individuals with TAR syndrome have a minimally deleted 200-kb region at chromosome band 1q21.1 which is necessary but not sufficient to cause the phenotype. Thus, identification of the 200-kb minimally deleted region confirms the diagnosis of TAR syndrome in individuals with bilateral absence of the radius and presence of thumbs.
17) Which is not related to non-disjunction in the mother?
a) Turners
b) Klinefelters
c) XXX
A. Turner’s. The single X is maternal in origin in about 70% of cases, i.e. the sex chromosome lost is paternal in origin. Klinefelters (XXY) results from errors in paternal meiosis I about ½ the time and from maternal meisosi about ½ the time. Almost all cases of XXX result from errors in maternal meiosis.
18) What other anomaly is most commonly seen with a diaphragmatic hernia?
a) Cardiac
b) Renal
c) Neuro
) A. Cardiac
20) What is increased with paternal age?
a) Achondroplasia
b) Cystic Fibrosis
c) Down Syndrome
A. Achondroplasia. Advanced paternal age results in increased risk of autosomal dominant, single gene disorders with spontaneous mutations.
21) What is the risk of Down syndrome with a prior effected child?
a) 1%
b) 5%
c) 16%
d) 20%
A. 1% or the age related risk, whichever is higher.
22) What is seen with Meckles syndrome?
a) Renal agenesis
b) Polycystic Dysplastic kidneys
c) Normal kidneys
B. Polycystic dysplastic kidneys. Meckel Gruber syndrome is characterized by polycystic dysplastic kidneys, encephalocele, polydactyly, pulmonary hypoplasia. It is an autosomal recessive disorder characterized as a celiopathy.
24) Which maternal cardiac lesion is associated with the greatest fetal risk?
a) AS
b) VSD
c) TOF
d) MS
A. Aortic stenosis with a 15-18% risk of transmission to the fetus.
25) 45,XX,der(13,21)(q10q10) associated with?
a) Normal
b) Lab error
c) Down syndrome
d) From father
) A. Normal. This is a balanced robertsonian translocation of 13q21q.
26) Which is associated with uniparental disomy?
Uniparental disomy occurs when a disomic (euploid) cell line contains 2 chromosomes inherited only from one parent. Examples are Prader-Willi, Angelman, and Beckwith-Wiedemann (chromosome 11). It also occurs from a trisomic rescue – i.e. you’ll see a trisomy 13 in CVS, the fetus tries to save itself by losing a chromosome 13 but loses the wrong one and gets a uniparental disomy.
27) Imprinting is?
Imprinting is the phenomenon of differnet expression of alleles depending on the parent of origin. May be due to methylation.
28) Most likely to transmit to fetus?
a) ASD
b) VSD
c) Coarctation
Coarctation
Most likely associated with aneuploidy?
a) Cardiac defect
b) Omphalocele
The risk of aneuploidy in omphalocele is 30-40%; the risk of chromosomal defects in live births with congenital heart disease is 5-15%.
31) CDH in term infant?
a) Cardiac
b) Stillbirth
c) CNS
Congenital heart diseease constitutes the majority of associated anomalies seen in CDH (Callen does not give a percentage). The incidence of abnormal karyotype is 10%, but may rise to 20% if multiple anomalies are present. Polyhydramnios occurs in 75%.
32) AF acetylcholinesterase least helpful in?
a) Omphalocele
b) Gastroschisis
c) Congenital nephrosis
d) Anencephaly
C. Congenital nephrosis. Amniotic fluid acetylcholinesterase is not elevated in congenital nephrosis but is elevated in open neural tube defects, gastroschisis, and omphalocele.
Timing of midgut herniation
Physiologic midgut herniation occurs during the 6th week of development & the intestin returns to the abdominal cavity by the 10th week. Normal herniation is observed in 64% of fetuses at 8 weeks, 100% at 9-10 wks, & 25% at 11 weeks, & 0% at 12 weeks.
36) Triple screen with really high AFP , no NTD:all except
a) chorioangioma
b) umbilical cord cyst
c) subchorionic hemorrhage
d) velamentous cord insertion
D. Velamentous cord insertion – found an article that stated velamentous cord insertion associated with slightly decreased MSAFP & increased hCG. Umbilical cord cysts can be associated with trisomies or abdominal wall defects, which would be associated with elevated AFP. (Disclosure – other people have answered umbilical cord cyst with some consistency in the study materials, but I can’t find any support for that answer)
