BOOTCAMP 2 Flashcards
What is Turner syndrome?
A genetic condition in which a female is partially or completely missing an X chromosome, commonly with a 45, XO karyotype due to paternal meiotic nondisjunction.
What is mosaic Turner syndrome?
A subtype where some cells have 45, XO and others have 46, XX, usually from mitotic nondisjunction, leading to milder features and increased risk of gonadoblastoma
What is the difference between germline and somatic mosaicism?
Germline mosaicism involves multiple gamete lineages passed to offspring (e.g., in osteogenesis imperfecta), while somatic mosaicism involves multiple cell lineages in somatic cells, not passed to offspring (e.g., in Down syndrome).
How does mosaic Turner syndrome develop?
It arises when the X chromosome is lost during early embryonic cell division, resulting in a mix of 45, XO and 46, XX cells.
Acute myelogenous leukemia (AML) is a malignancy of myeloblasts. Risk factors include prior exposure to alkylating chemotherapeutic agents, radiation, myeloproliferative disorders, and Down syndrome (trisomy 21). Clinical features include
Pancytopenia, with lymphadenopathy and hepatosplenomegaly being less common than acute lymphoblastic leukemia (ALL).
Lynch syndrome, hereditary nonpolyposis colorectal cancer (HNPCC), is an inherited syndrome. It also involves the two-hit hypothesis. A germline mutation in MLH1 and MSH2 DNA mismatch repair genes (increased nucleotide changes and microsatellite stability) is present at birth, and a later mutation inactivates the second allele. Patients may present with a familial history of colorectal cancer. ? is the most common non-colon malignancy in these patients, but the development of ovarian cancer is also common (epithelial serous subtype).
Endometrial cancer
Neuroblastoma is the most common adrenal medullary tumor, frequently occurring in children. It is derived from neural crest cells and involves overexpression of the n-myc proto-oncogene. Clinical features include
Abdominal pain, distension (mass effect), and opsoclonus-myoclonus syndrome (rapid eye movements, rhythmic jerking) +/- ataxia.
Retinoblastoma results from the inactivation of both alleles of the RB1 gene. It classically presents in the first three years of life, with ?. Retinoblastoma involves the two-hit hypothesis; tumor suppressor genes require both alleles to be inactivated (e.g., mutation, imprinting). In affected individuals, one RB1 gene is mutated in all cells at birth (germline mutation), and a second somatic mutation or “hit” occurs after birth.
Leukocoria (white pupillary reflex), strabismus, and a creamy-white mass on fundoscopy.
What is erythema infectiosum, and what are its key clinical features?
Commonly known as fifth disease, it presents with constitutional symptoms (fever, headache) and a “slapped-cheek” rash, usually sparing the nasolabial folds.
What causes erythema infectiosum, and what are its key symptoms?
Caused by parvovirus B19, it starts with a 1-2 week prodrome of congestion, headache, fever, and malaise, followed by a lacy rash on the trunk and extremities.
Describe parvovirus B19
It is a nonenveloped, single-stranded DNA virus that causes various conditions, including hydrops fetalis and arthritis, and attaches to globoside (blood group P antigen) a glycosphingolipid cellular receptor found on erythroid precursors (e.g., erythroblasts, megakaryocytes), erythrocytes, and various other cells (e.g., placental syncytiotrophoblasts, fetal cardiomyocytes, endothelial cells).
How does parvovirus B19 affect the body?
It replicates in the nucleus of erythroid precursor cells in the bone marrow, causing cell lysis and the release of mature virions. Individuals lacking P antigen are resistant to infection.
Individuals who lack P antigen are naturally resistant to
Parvovirus B19 infection
EBV is typically transferred by direct contact via saliva. The virus then enters the bloodstream through the tonsillar crypts and pharyngeal mucosa, preferentially infecting B lymphocytes by binding to ? via a viral envelop glycoprotein called gp350/220. These EBV-infected B lymphocytes can then activate cytotoxic T lymphocytes by presenting viral antigens on MHC class I molecules.
CD21 (also called CR2)
Rhinovirus is a nonenveloped, single-stranded, positive-sense, acid-labile, linear RNA virus. It binds to ?, found on nasopharyngeal and adenoid epithelial cells.
Intracellular adhesion molecule-1 (ICAM-1)
Cytomegalovirus (CMV) is a human herpesvirus that can spread via sexual transmission, direct contact, blood or tissue exposure, or perinatally. Cellular integrins function as entry receptors for this virus. Binding results in the activation of
Integrin-specific signal transduction pathways.
Rabies virus is an enveloped, single-stranded, negative-sense, linear RNA virus that contains a bullet-shaped envelope. Its envelope has knob-like glycoproteins that allow it to attach to the ? at the neuromuscular junction.
Nicotinic acetylcholine receptor
Positive if Induration is:
> 5 mm: Immunosuppressed, HIV positive, recent contact with active TB, signs of prior TB on CXR.
10 mm: Immigrated from endemic areas, works in high-risk environments, intravenous drug users, children < 4 years, certain chronic medical conditions.
15 mm: Positive for all other individuals not falling into groups A or B.
PPD Skin Test Positivity Criteria
Process:
Injection of tuberculin protein into the skin.
Reevaluation 48-72 hours later to measure induration (not erythema).
PPD Testing Procedure
Type of Reaction:
- Type IV Cell-Mediated Hypersensitivity Reaction:
Pre-sensitized T cells respond to tuberculin antigens.
T cells release cytokines, activating macrophages and causing local inflammation.
Mechanism of PPD Test
- A positive test suggests likely infection with tuberculosis (active or latent).
- Does not differentiate between active and latent TB infection.
Interpretation of PPD Test Results
Examples Include:
- Contact dermatitis
- Stevens-Johnson syndrome
- Toxic epidermal necrolysis
- Drug reaction with eosinophilia and systemic symptoms (DRESS)
- Multiple sclerosis
- Type I diabetes mellitus
- Hashimoto’s thyroiditis
Other Type IV Hypersensitivity Reactions
Type I: Anaphylaxis (mediated by IgE).
Type II: Hemolytic transfusion reactions, Graves’ disease (antibody-mediated).
Type III: Post-streptococcal glomerulonephritis (immune complex-mediated).
Comparison to Other Hypersensitivity Types
What are the common symptoms and laboratory findings associated with poststreptococcal glomerulonephritis (PSGN) in children?
Symptoms include dark urine, facial and periorbital edema, and hypertension. Laboratory findings typically show brown urine, proteinuria (< 3.5 g/day), RBC casts, elevated anti-streptolysin O titers, and decreased complement (C3) levels.
What is the underlying mechanism of poststreptococcal glomerulonephritis (PSGN) and how does it present on immunofluorescence?
PSGN is a type III hypersensitivity reaction occurring 2-4 weeks after a group-A streptococcal infection. On immunofluorescence, it shows a “lumpy-bumpy” pattern due to subepithelial immune complexes (IgG, IgM, C3) with normal serum C4 levels.
Can be seen during, or immediately after, a respiratory or gastrointestinal infection. Additionally, it is mostly seen in males in their second or third decade of life.
IgA nephropathy (Berger disease)
Chronic Myeloid Leukemia (CML) Overview
CML is commonly caused by the t(9;22) translocation, leading to an abnormal tyrosine kinase protein. Clinical features include constitutional symptoms (fatigue, weight loss, myalgias) and splenomegaly. CML can transform into acute leukemia (AML, ALL) during a blast crisis.
Neurofibromatosis Type II
Results from a mutation in the NF2 tumor suppressor gene on chromosome 22, coding for the protein merlin. Patients are at risk for bilateral acoustic neuromas and meningiomas.
Von Hippel-Lindau Disease
An autosomal dominant condition due to a mutation in the VHL tumor suppressor gene on chromosome 3, affecting hypoxia-inducible factor ubiquitination. Patients are at risk for cerebellar and retinal hemangioblastomas, pheochromocytoma, and renal cell carcinoma (clear cell subtype).
