Genetics 8: monosomies and trisomies Flashcards
Describe these in terms of ratios. Meta centric chromosome Submetacentric Acrocentric Telocentric
Metacentric is 50/50
Submetacentric is 60/40
Acrocentric 80/20
Telocentric 100/0
Give example of a monosomy and a partial monosomy
Monosomy: Turner syndrome, XO
Partial monosomy: cri du chat, deletion of the short arm of chromosome 5
Name 3 main trisomies
Trisomy 13 : patau
Trisomy 18: Edwards
Trisomy 21: downs
What is the MC cause of Turner syndrome?
Non disjunction
What is going on In Turner’s syndrome?
One X chromosome is missing
In turners ysndrome, 30% of people are mosaics, that means what genotypes?
Some cells are 46 XX, others are 45 X0
Short stature, webbed neck, low set hairline, ovarian dysgenesis (streak ovaries) because fatty tissue has replaced the ovaries, no menarche or ovulation in females , horshoe kidney, shortened 4th metacarpal
Turner’s Syndrome
Lymphedema of hands and feet in the neonate is suggestive of
Turner’s Syndrome
The ovaries of a patient with Tuner syndrome cannot make these two hormones
Estrogen and progesterone
Three cardiac afflictions that can affect patients with Turner syndrome
Predictable coartación of the aorta. PRE ductal
Bicuspid aortic valve
Aortic dissection in adulthood
What is the main sx of coartación of the aorta ?
Diminished femoral pulses compared to brachial pulses
How to treat turners syndrome?
Surgery to fix webbed neck
Fix her coartación
Estrogen for second characteristics
Could do IVFertulization for having kids
Partial deletion of short arm in chromosome 5. Most commonly seen as sporadic mutation.
Cri du chat syndrome
Abnormal development of the larynx and the nervous system,
Cri du chat
One year old with feeling problems, low birth weight, cognitive and speech delays,
Motor delays, aggression, hyperactivity, tantrums, excessive drooling, wide eyes, small head and jaw, cat-like squeal.
Cri du chat
Chromosome 5
MCC sporadic mutation
Chromosomes that can undergo robertsonian translocations
13, 14, 15, 21 and 22
Sx of patau, chromosome?
Low set ears. Polydactyly, abnormal palm patterns, clef palate, lip palate. Coloboma (hole in the eye)?, malformed or absent nasal septum (nose), ringers overlapping thumb, rocker bottom feet (not just seen in Edwards syndrome), abdominal wall defects like omohalocele (extruded but covered intestinal organs),
Chromosome, 13, trisomy 13
Second most common trisomy?
Trisomy 18, Edwards Syndrome
Most common trisomy?
Trisomy 21, downs.
Sx in Edwards Syndrome? Chromosome?
Trisomy 18
Sx: Low set and malformed ears, prominent occiput, micrognathia, microstomia, microcephaly, Arnold chiari y malformatio, severe mental retardation, delayed psychomotor development, clenched hands with overlapping fingers (fists), rocker bottom feet, short sternum, hypertonia, VSD, PDA in heart, in GI- meckels diverticulum, malrotation .
Most common chromosomal abnormality, 1 of 3 most common causes of mental retardation, meotic II non disjunction (increased risk with matarla age)
Down’s syndrome
Triple test for Down’s syndrome during weeks 16-18 of gestation looks for low levels of which tree substances?
Low AFP
Low B- hCGH
Low estradiol
If low AFP found, then next step to Dx Down syndrome is to do what?
Amniocentesis is gold standard then karyotype
What is a mosaic Down syndrome patient?
Their IQ is said to be 10-30 points higher. They will probably be able to function on their own, and Hold a simple job.
Sx in Down’s syndrome
Low set ears, palpebral fissure (eyes), flat nasal bridge, muscle hypotonia, Simeon crease (single palmar fold), protruding tongue (due to small mouth), joint laxity (Atlanto- axial joint), wide space between the big and the second toe.
Cardiac sx in Down’s syndrome
Present in up to 50% of patients.
Endocardium cushion defect (ASD is most common)
VSD is second most common.
What two hematologic/cancer conditions are patients of Down’s syndrome most at risk?
AML (M7) after 12 years old, I,e, sometime in their lifetime
And
From birth to 12 years old, ALL (10 to 20x increased risk)
What immunological maladies are patients with Down’s syndrome most prone to?
Impaired cellular immunity
High incidence of infections
High incidence of autoimmune disorders and malignancies
What type of cells are seen most in AML?
Auer rods
What organ specific findings are seen in Down’s syndrome?
Atherosclerosis risk is increased leading to neuropathies.
What endocrine maladies am Down syndrome patients have?
MOs common is hypothyroidism. Buy hyper is also possible. Also
Type 1 DM
Infertility in males
subfertility in females 30-50%
What are the most important neurological risks in patients with Downs syndrome?
They have an extra copy of the APP gene on chromosome 21. So they are at risk for early Alzheimer’s. Early means before 60. So accumulation of A beta amyloid in brain tissue and vessels.
And
Mental retardation, hearing impairment.
What are the GI afflictions most likely in a patient with Down’s syndrome? Name 6
Hirschsprung disease. Duodenal atresia Annular pancreas Imperforate anus GERD Celiac disease
What’s the most common karyotype of kilnefelters disease?
47 XXy
What is the physical appearance in a person with klinefekter?
Eunuchoid body habitus : tall, gynecomastia, no secondary characteristics male , mild mental retardation. But majority have NORMAL intelligence, Absence of body hair, absence of facial hair, muscle mass is decreased.
What are two variations of klinefeter karyotype?
48 XXXY
46XY/46 XXY mosaic
Phenotypically this neonate is normal. Signs of this disease are evident in liberty. Hyooginadism. Reduced soermatigenesis, male infertility
Klinefekter Syndrome
47 XXY
Klinefekter sx: Testicular? FSH? LH? Testosterone? Size of testes? Sexual characteristics?
Testicular failure No testosterone synthesis FSH and LH are increased Testes Small, firm Azoospermia, infertility, No secondary characteristics
In Klinefelter syndrome the more —- the patients have, the more severe the retardation.
The more X chromosomes the more severe the mental retardation.
Deletion of long arm of chromosome 22
DiGeorge Syndrome
Sx of di george
Thrymic aplasia, failure of parathyroid, cardiac afflictions
Sx in di George are caused by defective embryonic development of
3rd and 4th pharyngeal pouches
Immunological consequence of thymus aplasia
No T cells, viral infections risk increases a lot.
Hypocalcemia tetany, recurrent viral and fungal infections, y cardiac defects such as tetralogy of fallot, Clift palate
Di george
Mental delays, hand flapping, frequent smiling, happy de años, genes maternally inherited
Angelman, chromosome 15
Short stature, hypotonia, marrow temples, elongated face, thing upper lip, prominent nose, hyperphagia, severe obesity, increased risk for DM, hypodevelooment of sxual organs, 50-70 IQ, imprinting or deletion of paternal all chromosome
Chromosome 15, Prader willi syndrome
What is early onset Alzheimer’s?
Less than 60 years old
Three mutations associated with EARLY Alzheimer’s disease?
- APP gene on Chr 21
- Presenillin 1 gene on chr 14
- Presenillin 2 gene in chr 1
Mutation associated with LATE Alzheimer’s disease?
APO e4 allele of the Apoprotein E - causes senile plaques
Senile plaques are ——- the cell
Extra cellular
Neurofibrillary tangles are —— the cell
Intro cellular
