Genetic Disorders Flashcards
Down syndrome
-genetics, common characteristics, associations
Genetics: meiotic nondisjunction, robertsonian translocation, mosaicism
Characteristics:
- a/w advanced maternal age
- upslanted eyes, simian crease, general hypotonia
- flat facial profile, mental retardation, atlantoaxial instability, extra neck folds
a/w:
- duodenal artresia, Hirschsprung dz, congenital heart dz (ASD, VSD, PDA)
- increased risk of ALL, hypothyroidism, and early-onset Alzheimers
In utero: low AFP, low estriol, elevated B-hcg, elevated inhibin A
Edwards syndrome
-genetics, common characteristics, associations
Trisomy 18
Common characteristics:
- severe mental retardation
- rocker-bottom feet, low-set ears, micrognathia, clenched hands (overlapping 4th and 5th digit) and prominent occiput
a/w:
- congenital heart dz, horseshoe kidney
- death occurs in one year
In utero: low AFP, estriol, B-hcg, inhibin A
Patau’s syndrome
-genetics, common characteristics, associations
Trisomy 13
Common characteristics
- severe mental retardation
- micropthalmia, microcephaly, holoprosencephaly, polydactyly
- cleft lip/palate, punched out scalp lesions, omphalocele
a/w:
- congenital heart disease
- death occurs in one year
Klinefelter’s syndrome
-genetics, common characteristics, associations
47XXY
Common characteristics:
- characterized by presence on inactivated X chromosome (Barr body)
- testicular atrophy, tall stature, gynecomastia, female hair distribution, long extremities, eunuchoid body shape
Associations:
- advanced maternal age
- one of the most common causes of hypogonadism
Treat w/ testosterone
Turner’s syndrome
-genetics, common characteristics, associations
45, XO
-missing 1 x chromosome
Common characteristics:
- most common cause of primary amenorrhea 2/2 ovarian dysgenesis (decreased estrogen)
- short stature, shield chest, webbed neck, coarctation of the aorta
- may present w/ lymphedema of hands and feet
- may have horseshoe kidney
Double Y males
47, XYY
Observed w/ increased frequency of inmates in penal institutions
Phenotypically normal; patients are very tall w/ severe acne and antisocial behavior
PKU
-genetics, common characteristics, associations
AR dz of decreased phenylalanine hydroxylae or decreased tetrahydrobiopterin cofactor (required for phenylalanine hydroxylase)
Common characteristics:
- tyrosine becomes essential and phenylalanine builds up
- normal at birth, presents in first few months
- mental retardation, fair hair and skin, eczema, blond hair, blue eyes, musty urine odor
Associations:
-increased risk of heart dz
Tx:
-decreasing phenylalanine ingestsion, increasing tyrosine ingestion
Fragile X syndrome
X-linked dominant dz affecting methylation and expression of the FMR1 gene
Clinical characteristics:
- 2nd most common cause of genetic mental retardation
- large jaw, testes, and ears w/ autistic behavior
Triplet repeat disorder that may show genetic adaptation
Cystic Fibrosis
AR dz of the CFTR gene
Hx/PE:
- FTT or chronic sinupulmonary dz
- recurrent pulm infxns (Pseudomonas or S. aureus), digital clubbing, chronic cough, bronchiectasis, nasal polyps
- meconium ileus (bilious vomiting in newborn)
- GI sx: greasy stools/flatulence; pancreatitis, rectal prolapse, hypoproteinemia, biliary cirrhosis, jaundice, esophageal varices
- type 2 DM, salty-tasting skin, male infertility (2/2 agenesis of vas deferens), unexplained hyponatremia
- fat-soluble vitamin deficiency 2/2 malabsorption
Dx:
- sweat chloride >60 or >80
- genetic testing
- ABG = hypochloremic alkalosis
- mandatory newborn screening, occasional false positives
Tx:
- pulm manifestations: chest physical therapy, bronchodilators, corticosteroids, antibiotics (w/ Pseudomonal coverage)
- pancreatic enzymes and fat-soluble vitamins
Risk factors for intussusception
Meckel's diverticulum intestinal lymphoma HSP parasites polyps adenovirus rotavirus celiac dz CF
Hirschsprung disease associations
Down syndrome
male gender
Waardenburg’s syndrome
MEN type 2
Bruton’s agammaglobulinemia
-what cell, genetics, pathophys
B cell disorder
X-linked recessive B cell deficiency
Symptoms begin at 6 months; life threatening dz, 2/2 infxn by encapsulated Pseudomonas because of lack of immunoglobulin’s
Common variable immunodeficiency (CVID)
-what cell, pathophys, tx
B and T cell defect All Ig levels are low Normal B cell numbers, but decreased plasma cells Symptoms present later in life Treat w/ IVIG
IgA deficiency
-transfusions: what happens?
Decreased IgA, most common immunodeficiency
a/w recurrent Giardia infection
Anyphalactic response to transfusions 2/2 anti-IgA abs
DO NOT GIVE IVIG (can sensitize)
DiGeorge syndrome
-what cell, constellation of sx, common infections, treatment
Absent thymus = decreased T cells
CATCH22
-Congenital heart defects, abnormal facies, thymic hypoplasia, cleft palage, hypocalcemia, 22q11 deletion
Common infections: virus, fungi, PCP
Tx: IVIG, PCP ppx, bone marrow transplantation
Ataxia-telangiectasia
-pathophysiology, associations
Cerebellar ataxia and oculocutaneous telangiectasias
2/2 DNA repair defect
a/w increased incidence of malignancies (NHL, leukemia, gastric cancers)
SCID
-what cells, what enzyme
Lack of B and T cells 2/2 defect in stem cell maturation
Enzyme: decreased adenosine deaminase
Tx: BM transplant, IVIG, PCP ppx
Wiskott-Aldrich syndrome
-genetics, immunodeficiency, presentation
X-linked recessive disorder, only in males
Increased IgE and IgA, but decrease in IgM and platelet count
Classic presentation: bleeding, eczema, recurrent otitis media. WIPE = Wiskott-Aldrich, Infections, pupura (2/2 thrombocytopenia), and eczema
-increased risk of atopic disorders, lymphoma/leukemia, and encapsulated infxns
Patients rarely survive to adulthood
Chronic granulomatous disease
-genetics, what enzyme, what organisms are common, common infected systems, diagnostic test, tx
X-linked or AR dz. Missing superoxide Infecting organisms are catalase + -S. aureus, Candida, E. coli, Klebsiella, Pseudomonas, Aspergillus Commonly infects skin, GU, GI, plum -granulomas of skin may be seen
Dx: nitroblue tetrazolium test is diagnostic
Tx: daily TMP-SMX, IFN-gamma can decrease incidence
Leukocyte adhesion deficiency
-defect, common sites of infection
Defect in chemotaxis of leukocytes
Recurrent skin, mucosa, and pulm infxns
-can have ophmalitis in newborn w/ delayed separation of umbilical cord (CLASSIC)
Chediak-Higashi syndrome
-genetics, defect, clinical manifestations, common infections, dx
AR dz. Defect in neutrophil chemotaxis/microtubule polymerization
Clinical: oculocutaneous albinism, peripheral neuropathy, neutropenia
Increased risk of pyogenic infxns w/ GAS, S. aureus, and Psuedomonas
Dx: giant granules in nuetrophils
Job’s syndrome
-defect, clinical manifestations, infections
Defect in neutrophil chemotaxis
FATED:
-coarse Facies, Abscesses, retained primary Teeth, hype-igE (eosinophilia), Dermatologic (severe eczema)
C1 esterase deficiency
Complement deficiency: common in congenital aspenia or splenic dysfxn
aka hereditary angioedema
AD disorder w/ recurrent angioedema for 2-72 hours (2/2 increased bradykinin and C2b)
-provoked by stress or trauma
-can be life threatening if it causes laryngeal edema
Dx: total hemolytic complement (CH50) to assess quantity and function
-purified C1 esterase and FFP can be used prior to surgery
Terminal complement deficiency
Complement deficiency: common in congenital aspenia or splenic dysfxn
C5-C9
inability to form MAC
Recurrent Neisseria infections (both meningococcal and gonococcal)
-rarely causes SLE or glomerulonephritis
