DIT review - Reproduction 3 Flashcards
1
Q
Most common #1 and #2 cause of genetic intellectual disability + most common cause overall
A
1 genetic cause = Trisomy 21
Most common cause overall = Fetal alcohol syndrome
2
Q
Quad screen values in trisomy 21
A
- Decreased alpha-fetoprotein
- Increased b-hCG
- Decreased estriol
- Increased Inhibin A
3
Q
Genetic causes of trisomy 21
A
- 95% due to meiotic nondisjunction
- 4% due to unbalanced Robertsonian translocation (between chromosome 14 and 21)
- 1% due to mosaicism
4
Q
Presentation of Edwards Syndrome
A
Trisomy 18
- Prominent occiput
- Rocker-bottom feet
- Intellectual disability
- Clenched fists
- Low set ears
- Micrognathia (small jaw)
- Death usually by age 1
5
Q
Quad screen values in trisomy 18
A
- Decreased alpha-fetoprotein
- Decreased b-hCG
- Decreased estriol
- Normal Inhibin A
6
Q
Presentation of Patau syndrome
A
Trisomy 13
- Intellectual disability
- Rocker bottom feet
- Microphthalmia
- Microcephaly
- Cleft lip/palate
- Holoprosencephaly
- Death usually by age 1
7
Q
Abnormal values of first trimester pregnancy screen in Trisomy 13
A
- Decreased b-hCG
- Decreases PAPP-A (pregnancy-associated plasma protein A)
- Increased nuchal translucency
8
Q
Trinucleotide repeat and gene involved in Fragile X
A
- Trinucleotide repeat – CGG
- FMR1 gene (THINK: Fragile Mental Retardation)
9
Q
Presentation of Fragile X
A
- Macroorchidism
- Long face
- Long everted ears
- Autism
- Mitral valve prolapse
- Intellectual disability
10
Q
Chromosome abnormality and presentation of Klinefelter syndrome
A
- 47, XXY
- All male
- Testicular atrophy, eunuchiod body shape, tall, long extremities, gynecomastia, female hair distribution
- THINK: Charlie
- Presence of barr body (inactivated X chromosome)
- Dysgenesis of seminiferous tubules à decreased inhibin B à increased FSH
11
Q
Chromosome abnormality and presentation of Turner syndrome (what is the cardiac abnormality?)
A
- 45, XO
- All female
- Short stature, broad (shield) chest, webbed neck, streak ovary (lack of paternal X chromosome causes loss of follicles within the ovary by age 2), bicuspid aortic valve, coarctation (femoral < brachial pulse), horshoe kidney
- Most common cause of primary amenorrhea
- Decreased estrogen will cause increased LH and FSH
12
Q
Presentation of Double Y Males (XYY)
A
- 47, XYY
- Phenotypically normal
- Very tall, severe acne
- May have antisocial behaviors
13
Q
Mutation and presentation of Cri-du-Chat syndrome
A
- Microdeletion of short arm of chromosome 5 (45, XX or 45, XY, 5p-)
- Microcephaly, intellectual disability, high pitched crying/mewing, cardiac abnormalities
- THINK: Cry of the Cat
14
Q
Mutation and presentation of Williams syndrome
A
- Microdeletion of long arm of chromosome 7 (deletion includes elastin gene)
- “Elfin” facies, intellectual disability, hypercalcemia, well-developed verbal skills, extreme friendliess with strangers
- THINK: Will Ferrel in the movie elf
15
Q
What is the defect in Li-Fraumeni syndrome
A
- Defective p53 (tumor suppressor) - multiple malignancies at an early age
16
Q
What is the mutaiton in Neurofibromatosis type 1
A
- Caused by mutation in NF1 gene on chromosome 17
- This gene is responsible for control of cell division
17
Q
Presentation of NF Type 1
A
- Neurocutaneous disorder characterized by café-au-lait spots, cutaneous neurofibromas, optic gliomas, pheochromocytomas, Lisch nodules (pigmented iris hamartomas)
18
Q
What is the mutation of neurofibromatosis type 2
A
- Due to mutation of NF2 gene on chromosome 22
19
Q
Presentation of Neurofibromatosis type 2
A
- Presentation:
- Hearing loss, tinnitus, balance problems, hyperpigmented skin lesions, cataracts
- REMEMBER 2’s:
- Chr 22
- Bilateral hearing loss
- NF Type 2
- Cataracts
20
Q
Mutation in Autosomal Dominant Polycystic Kidney Disease (ADPCKD)
A
- Due to mutation in APKD1 on chromosome 16
21
Q
Presentation of ADPCDK
A
- Numerous cysts in cortex and medulla causing bilateral enlarged kidneys
- Presentation:
- Flank pain, hematuria, HTN, UTI, progressive renal failure
- Also associated with Berry aneurysms, mitral valve, prolapse, and liver disease
22
Q
Mutation in achondroplasia
A
- Defect of FGFR3 (gain-of-function)
- Normally responsible for inhibition of cartilage proliferation
- Associated with advanced paternal age
23
Q
Presentation of achondroplasia
A
- Failure of longitudinal (endochondral) bone growth à short limbs
- Intramembranous bone (forms without preexisting cartilage matrix) is fine
- Normal skull and chest
24
Q
Mutation in familal adenomatous polyposis (FAP)
A
- Due to mutation of APC tumor suppressor on chromosome 5q
25
Presentation of FAP
* Thousands of polyps presenting after puberty
* 100% progression to colorectal cancer without colectomy
26
Presentation of Gardner syndrome
* Familial adenomatous polyposis + tumors outside the colon
* Osteomas / soft tissue tumors
* Supernumerary teeth
* THINK: Gardener from the Kaposi sketchy
* Digging through haustra-shaped planters à FAP
* Digs up a bone à osteoma
* Old lady smiles with extra teeth à supernumerary teeth
27
Defect in Familial Hypercholesterolemia
* Increased LDL due to defective or absent LDL receptor
28
Presentation of familial hypercholesterolemia
* Accelerated atherosclerosis (early MI), tendon xanthomas, corneal areus
29
Presentation of Hereditary hemorrhagic telangiectasia
* Aka Osler-Weber-Rendu syndrome
* Inherited disorder of blood vessels
* Presentation:
* Telangiectasias, recurrent epistaxis, skin discoloration, arteriovenous malformations, Gi bleeding, hematuria
30
Defect in hereditary spherocytosis
* Due to defect in spectrin or Ankyrin (defect in structural framework for RBC)
* Loss of membrane blebs causes spherocytes
* Spherocytes cannot maneuver through spleen so are consumed by splenic macrophages
31
Presentation, diagnosis, and treatment of hereditary spherocytosis
* Presentation:
* Spherocytes, splenomegaly, jaundice, aplastic crisis, increased MCHC
* Diagnosis:
* Abnormal osmotic fragility test
* Treatment:
* Splenectomy
32
Main characteristics of Huntington disease
* C’s of disease:
* Cognitive decline
* Caudate atrophy
* Chorea
* CAG repeat
* Chromosome cuatro (4)
* Cuarents (40 y/o)
* Decreased AcetylCholine
33
Mutation in Marfan syndrome
§ Due to mutation in fibrillin gene (FBN1) which codes for a protein responsible for the production and maintenance of elastin fibers
34
Presentation of Marfan
· Arachnodactyly
· Lens dislocation (upward)
· Floppy mitral valve (regurgitation)
· Thoracic aortic dissection
· Hyperflexible joints
35
Mutation in Tuberous Sclerosis
* Due to mutated hamartin (or tuberin) gene
* TSC1/TSC2 mutation on chromosome 16
* Incomplete penetrance and variable presentation
36
Presentation of Tuberous sclerosis
* Triad:
* Angiofibromas, mental retardation, seizures
* Other symptoms: Ash-leaf spots, hamartomas of CNS and skin, angiomyolipoma
37
Mutation of von Hippel-Lindau disease
* Deletion of VHL gene on chromosome 3p
38
Presentation of VHL disease
* Presentation = HARP
* Hemangioblastoma (retina, brainstem, cerebellum)
* Angiomatosis
* bilateral Renal cell carcinoma
* Pheochromocytoma
39
Most common benign tumor of the breast
Fibroadenoma
40
Most common breast tumor
Invasive ductal carcionma
41
Presentation of fibrocystic change of the breast
* Most common change in premenopausal breast
* “Lumpy bumpy” breast, often bilateral
* Hormone sensitive – presents with premenstrual breast pain
* Cysts have a blue dome appearance on gross exam
42
Presentation of fibroadenoma of the breast
* Small, well-defined, mobile mass
* Hormone sensitivity – increased size and tenderness with estrogen
Mostly in women \< 35 y/
43
Describe sclerosing adenosis of the breast
* Too many glands in the terminal duct + fibrosis in between
* Often calcified
44
Describe intraductal papilloma of the breast
* Too many glands in the terminal duct + fibrosis in between
* Often calcified
45
Describe Phyllodes tumor
* Large mass of connective tissue and cysts with “leaf-like” projections on biopsy
* Some may be malignant
46
Most important prognostic factor of breast cancer?
Axillary lymph node involvment
47
Describe ductal carcinomal in situ
* Malignant proliferation of cells in ducts with no invasion of basement membrane
* Often presents as calcification of mammography
* Often progresses to invasive ductal carcinoma
48
Describe comedocarcinoma of the breast
* DCIS with central necrosis
49
Presentation of invasive ductal carcinoma of the breast
* Most common of all breast cancers
* Firm, fibrous, immobile, “rock hard” mass with sharp margins
* Distinguish from fibroadenoma due to immobility
50
Describe Paget disease of the breast
* Presents as eczematous patches on nipple
* Almost always results from underlying DCIS or invasive breast cancer
51
Describe lobular carcinoma in situ of the breast
* Malignant proliferation of cells in lobules
* Characterized by dyscohesive cells lacking E-cadherin
* Often does not progress to invasive lobular carcinoma
52
Describe invasive lobular carcinoma of the breast
* Grows in a single file pattern
* Cells may exhibit signet ring morphology
53
Describe inflammatory carcinoma of the breast
* Invasion of dermal lymphatics
* Peau d’orange (breast resembles an orange peel - dimpling)
