Biochem - Genetics (Special genetic disorders) Flashcards
Pg. 89-91 in First Aid 2014 Sections include: -Trinucleotide repeat expansion diseases -Autosomal trisomies -Robertsonian translocation -Cri-du-chat syndrome -Williams syndrome -22q11 deletion syndromes
What are 4 examples of trinucleotide repeat expansion diseases?
(1) Huntington disease (2) Myotonic dystrophy (3) Friedreich ataxia (4) fragile X syndrome; Think: “Try (trinucleotide) Hunting for My Fried Eggs (X)”
What is the trinucleotide repeat sequence of Fragile X syndrome?
Fragile X syndrome = (CGG)n
What is the trinucleotide repeat sequence of Freiderich ataxia?
Friedreich ataxia = (GAA)n
What is the trinucleotide repeat sequence of Huntington disease?
Huntington disease = (CAG)n
What is the trinucleotide repeat sequence of Myotonic dystrophy?
Myotonic dystrophy = (CTG)n
What genetic term/property may apply to trinucletoide repeat expansion diseases?
May show genetic anticipation (disease severity increases and age of onset decreases in successive generations)
Name the 4 trinucleotide repeat expansion diseases and give the specific repeat sequence of each.
(1) Fragile X syndrome = (CGG)n (2) Friedreich ataxia = (GAA)n (3) Huntington disease = (CAG)n (4) Myotonic dystrophy = (CTG)n; Think: “X-Girlfriend’s First Aid Helped Ace My Test”
Name 3 Autosomal trisomies.
(1) Down syndrome (trisomy 21) (2) Edwards syndrome (trisomy 18) (3) Patau syndrome (trisomy 13)
What is the genetic defect in Down syndrome? What are the chances of a patient having this condition?
Down syndrome (trisomy 21), 1:700; Think: “Drinking age (21)”
What is the genetic defect in Edwards syndrome? What are the chances of a patient having this condition?
Edwards syndrome (trisomy 18), 1:8000; Think: “Election age (18)”
What is the genetic defect in Patau syndrome? What are the chances of a patient having this condition?
Patau syndrome (trisomy 13), 1:15,000; Think: “Puberty (13)”
What are 9 clinical findings of Down syndrome?
Findings: (1) intellectual disability (2) flat facies (3) prominent epicanthal folds (4) single palmar crease (5) gap between 1st 2 toes (6) duodenal atresia (7) Hirschsprung disease (8) congenital heart disease (most commonly ostium primum-type atrial septal defect [ASD]) (9) Bruschfield spots.
What are 3 conditions for which Down syndrome patients have an increased risk?
Associated with increased risk of ALL, AML, and Alzheimer disease (> 35 years old).
What chromosomal event causes most Down syndrome cases? What percentage of cases does it cause? With what factor is this event associated, and what are the related statistics?
95% of cases due to meiotic nondisjunction of homologous chromosomes (associated with advanced maternal age; from 1:1500 in women < 20 to 1:25 in women > 45 years old).
What are 2 less frequently occurring (than meiotic nondisjunction of homologous chromosomes) events that cause Down syndrome? What percentage of cases does each of these cause?
4% of cases due to Robertsonian translocation; 1% of cases due to mosaicism (no maternal association; post-fertilization mitotic error)
What is the most common viable chromosomal disorder? Of what else is this the most common cause?
Down Syndrome; Most common viable chromosomal disorder and most common cause of genetic intellectual disability
What does first-trimester ultrasound of Down syndrome baby commonly show?
Increased nuchal translucency and hypoplastic nasal bone
What are 2 lab findings associated with Down syndrome in the first-trimester?
(1) serum PAPP-A is low (2) free beta-hCG is high
What 4 findings does second-trimester quad screen show in Down syndrome?
Second-trimester quad screen shows: (1) low alpha-fetoprotein, (2) high beta-hCG, (3) low estriol, (4) high inhibin A
What are 7 clinical findings associated with Edwards syndrome?
Findings: (1) severe intellectual disability (2) rocker-bottom feet (3) micrognathia (small jaw) (4) low-set ears (5) clenched hands (6) prominent occiput (7) congenital heart disease
What is the usual prognosis/outcome of Edwards syndrome?
Death usually occurs within 1 year of birth
What are 8 clinical findings associated with Patau syndrome?
Findings: (1) severe intellectual disability (2) rocker-bottom feet (3) microphthalmia (4) microcephaly (5) cleft liP/Palate (5) holoProsencephaly (6) Polydactyly (7) congenital heart disease
What is the usual prognosis/outcome of Patau syndrome? What other autosomal trisomy condition shares this?
Death usually occurs within 1 year of birth; Edwards syndrome
What is the second most common trisomy resulting in live birth? What is the first?
Edwards syndrome is the Most common trisomy resulting in live birth after Down syndrome
What are 2 key lab findings in first trimester with Edwards syndrome?
PAPP-A and free beta-hCG are decreased in first semester
What are 4 key findings of Edwards syndrome in quad screen?
Quad screen shows: (1) low alpha-fetoprotein (2) low beta-hCG (3) low estriol (4) low or normal inhibin A
What 3 findings does first-trimester pregnancy screen show in Patau syndrome?
First-trimester pregnancy screen shows: (1) low free beta-hCG (2) low PAPP-A and (3) high nuchal translucency.
Draw visuals depicting nondisjunctions in meiosis I versus meiosis II.
See p. 90 in First Aid 2014 for visuals at bottom of page
What is Robertsonian translocation? What 5 chromosome pairs does it commonly involve?
Nonreciprocal chromosomal translocation that commonly involves chromosome pairs 13, 14, 15, 21, and 22.
In general, how common is Robertsonian translocation?
One of the most common types of translocation
What causes Robertsonian translocation?
Occurs when the long arms of 2 arocentric chromosomes (chromosomes with centromeres near their ends) fuse at the centromere and the 2 short arms are lost
What phenotype results from balanced Robertsonian translocation?
Balanced translocations normally do not cause any abnormal phenotype
What are 3 consequences unbalanced Robertsonian translocation?
Unbalanced translocations can result in miscarriage, stillbirth, and chromosomal imbalance (e.g., Down syndrome, Patau syndrome).
What causes Cri-du-chat syndrome?
Congenital microdeletion of short arm of chromosome 5 (46,XX or XY, 5p-)
What are 5 clinical findings of Cri-du-chat syndrome?
Findings: (1) microcephaly (2) moderate to severe intellectual disability (3) high-pitched crying/MEWING (4) epicanthal folds (5) cardiac abnormalities (VSD); Think: “Cri du chat = cry of the CAT”
What causes Williams syndrome?
Congenital microdeletion of long arm of chromosome 7 (deleted region includes elastin gene)
What are 6 clinical findings of Williams syndrome?
Findings: (1) distinstinctive “elfin” facies (2) intellectual disability (3) hypercalcemia (high sensitivity to vitamin D) (4) well-developed verbal skills (5) extreme friendliness with strangers (6) cardiovascular problems
Describe the presentation of 22q11 deletion syndromes. Give 5 examples of signs/symptoms.
Variable presentation, including Cleft palate, Abnormal facies, Thymic aplasia –> T-cell deficiency, Cardiac defects, Hypocalcemia secondary to parathyroid aplasia, due to microdeletion at chromosome 22q11; Think: “CATCH-22”
What are the genetic and embryological causes of 22q11 deletion syndromes?
Due to microdeletion at chromosome 22q11; Due to aberrant development of 3rd and 4th branchial pouches
Give 2 examples of 22q11 deletion syndromes.
(1) DiGeorge syndrome (2) Velocardiofacial syndrome
What are 3 signs/symptoms in the presentation of DiGeorge syndrome?
DiGeorge syndrome - thymic, parathyroid, and cardiac defects
What are 3 signs/symptoms in the presentation of Velocardiofacial syndrome?
Velocardiofacial syndrome - palate, facial, and cardiac defects
