Disorders Flashcards
Flat facies, upturned palpebra fissures, microphthalmia, clinodactyly, sandal gap deformity, single palmer creases, hypotonia , microcephaly, Bushfield spots
Down Syndrome
Quad screen results: increased hCG, inhibin A; decreased AFP, estriol
Nuchal translucency
Why are people with Down Syndrome more likely to develop Alzheimer’s disease?
C21 has a gene that codes for amyloid precursor protein. Because individuals with DS has three copies of the gene, they generate higher amounts of amyloid.
Cat-like cry, microcephaly, hypertelorism, epicanthal folds, low set ears, microretrognathia, poor feeding, low birth weight
Cru-di-chat; caused by microdeletion of C5
Male, tall, underdeveloped secondary sexual characteristics, gynecomastia, language difficulties
Klinefelter Syndrome
Female, short, webbed neck, lymphedema, broad chest, cubitis valgas, hearing loss, edema of hands/feet, cardiac anomalies, renal abnormalities, delayed puberty
Turner Syndrome
Conotruncal cardiac anomalies (truncus arteriosus, tetralogy of Fallot, interrupted aortic arch), hypoplastic thymus (immunodeficiency), hypocalcemia (underdevelopment of parathyroid glands), variable craniofacial abnormalities (high arched palate, retrognathia, long face with prominent nose, hypertelorism, low-set ears, smooth philtrum), hypernasal speech, intellectual disability
DiGeorge Syndrome (22q11.2 deletion)
Cat eye syndrome
22q11.2 tetrasomy
MicroPhthalmia (small eyes)
Cutis aPlasia (holes in head)
HoloProsencephaly (hemispheres not separated)
Polydactyly
Polycystic kidney disease
Cleft lip and/or Palate
Also: Rocker bottom feet, clenched fists, microcephaly, severe intellectual disability, congenital heart disease (VSD, ASD), micrognathia, omphalocele
Patau syndrome (Trisomy 13)
Quad screen shows: decreased hCG, normal AFP, estriol and inhibin A
Edward Syndrome (Trisomy 18)
PRINCE Edward
Prominent occiput
Rocker Bottom Feet
Intellectual disability
Nondisjunction
Clenched fists with overlapping fingers
Ears, low set
Also: congenital heart disease
Quad screen shows: decreased AFP, hCG and estriol; normal or decreased inhibin A
“Elfin” facies, intellectual disabilities, hypercalcemia, supravalvular stenosis, renal artery stenosis, over-friendly children, problems with attention
Williams Syndrome; microdeletion of C7 - elastin gene
Elfin facies - broad forehead, elongated philtrum, short palpebral fissures, flattened nasal bridge
Hypercalcemia - not common in congenital diseases, due to increased Vit D activity
Paternal disomy, loss of maternal expression
Inappropriate laughter
Angelman Syndrome
Maternal disomy, loss of paternal expression
Uncontrolled hunger
Prader-Willi Syndrome
Fragile X syndrome
X-linked dominant inheritance - caused by CGG repeat expansion in FMR1 gene
Premutation: ataxia, ovarian insufficiency
Full mutation: Long narrow face, prominent forehead and jaw, large everted ears, mitral valve prolapse, above average head circumference, autistic, hyperactivity, language development
Anemic features: fatigue, lethargy, conjunctival pallor
Intermedia: present at birth w/jaundice, anemia
Major: not compatible with life
Target cells
alpha-thalassemia
alpha deletion on C16
Anemic features
hemolytic anemia, prominent skeletal (often facial) deformities
Target cells
Beta-thalassemia
B-gene point mutation on C11
Bernard-Soulier Syndrome
GpIb receptor deficiency - decreases adhesion
GpIb receptors are found on vWF which binds platelets to the injured endothelial cells
Increased BT(PFA), unaffected by Ristocetin (distinguishes BSS from GT)
Mucosal membrane bleeding, menorrhagia, easy bruising
Shows giant platelets on PBS
Glanzmann Thrombasthenia
GpIIB receptor deficiency - decreases aggregation
GpIIb receptors are found on platelets which binds fibrinogen
Increased BT(PFA), normal platelet count
Mucous membrane bleeding, easy bruising
Bernard-Sourlier Syndrome and Glanzmann Thombasthenia inheritance pattern
X-linked recessive
Hemophilia A (patho, tests, clinical, inheritance)
Factor VIII deficiency
Increased aPTT, normal platelet, BT(PFA), PT
Hemophilic arthropathy - hallmark for hemophilia
Melena (bloody stool), hematuria
X-linked recessive, Materal FHx
von Willebrand disease (patho, tests, clinical, inheritance)
Decreased vWF levels, decreased function of vWF, or no vWF at all
Increased BT(PFA), increased PTT, normal PT, normal platelet count
Autosomal dominant
Hemophilia B (patho, tests, clinical, inheritance)
Factor IX deficiency
Increased aPTT, normal platelet, BT(PFA), PT
Hemophilic arthropathy - hallmark for hemophilia
Melena, Hematuria
X-linked recessive, Maternal FHx
Pathogenesis, clinical presentation and diagnosis of ITP
Antibodies target GpIIb receptors on platelets - target platelets for destruction in the spleen
Clinical presentation: Epistaxis (nosebleeds), menorrhagia, petechiae, mucous membrane bleeding
Testing shows low platelet quantity, elevated bleeding time, increased megakaryocytes, giant platelet
Name the condition and cytogenic nomenclature
Trisomy 18 - Edwards Syndrome
47, XY, +18
Name the condition and cytogenic nomenclature
Deletion of C5 - Cru di chat
46, XY, del(5p)
Name the condition and cytogenic nomenclature
Additional X chromosome - Kleinfelter Syndrome
47, XXY
Name the condition and cytogenic nomenclature
Missing sex chromosome - Turner Syndrome
45, XO
Name the condition and cytogenic nomenclature
Trisomy 21 - Down Syndrome
47, XY, +21
Name the condition and cytogenic nomenclature
Trisomy 13 - Patau Syndrome
47, XX, +13
Name the condition and cytogenic nomenclature
Monosomy 14 - deletion C6
45, XX,-14,del(6q)
Poor prognosis - spontaneous abortion
What is the mode of inheritance?
Autosomal dominant
This shows autosomal dominant inheritance, what other factor could be involved?
Incomplete Penetrance
What is the mode of inheritance?
X-linked dominant
What is the mode of inheritance?
X-linked recessive
What medication can be used for vWF disease and what is it’s MOA?
Desmopressin
It increases vWF and factor VIII levels in the plasma by increasing the release of vWF from the endothelial cells
Neurofibromatosis type 1 (NF1) etiology and clinical presentation
What type of gene expression does it exhibit?
Mutation in NF1 gene
Development of Lisch nodules, cafe au lait spots, neurofibromas, and pheochromocytomas
Pleiotropy - a gene affecting multiple phenotypic traits
Clinical presentation and lab findings for Vitamin K deficiency
Hypovolemic - less volume in blood
Tachycardia - compensatory mechanism for low blood volume
Petechiae or ecchymosis
Low Hgb
Low MCV
Low Iron
Low Ferritin
High TBC
Showing Iron deficiency anemia
Prolonged PT, PTT, normal platelet count, Factor levels normal but function low
Why are patients with atherosclerosis at risk of arterial thrombus formation?
Build up of plaque can cause vessel occlusion which can cause venous stasis, or the turbulence going through the vessels can cause vWF to unwind.
Venous system is more fibrin rich, lower pressure and flow = more clots
Arterial system is more platelet rich, higher pressure and flow = more activation of platelets
Xeroderma Pigmentosum
Caused by defective Nucleotide excision repair
UV radiation causes thymidine dimers in the DNA which can’t be removed due to defective NER –> leads to other mutations
Autosomal recessive
Familial Adenomatous Polyposis
Defective Base Excision Repair
Autosomal Dominant defect of APC gene (WNT pathway)
or
Autosomal recessive defect in DNA glycosylase enzyme
Lynch Syndrome
Mismatch Repair Defect
Autosomal dominant mutation in MLH1 or MLH2 –> microsatellite instability, unstable number of repeating nucleotides
Leads to hereditary non-polyposis colorectal cancer
