DOMINANCE PATTERNS Flashcards
Gaucher’s disease
AR
NF type I
AD
Rett syndrome
X linked dominant
Marfan
AD
myoclonic epilepsy with red ragged fibers
Mitochondiral
Gilbert’s
AR
AD diseases: (18)
“Very Powerful Dominant Humans”
AD: HANNAAAHHHH MVMT POV
-VWF
-VHL
-Pseudohypoparathyroidism
-MyoTonic DysTrophia
-Osteogenesis Imperfecta
-Hereditary Hemorrhagic Telangiectasia
-Marfan
-Acute intermittent porphyria
-NF 1/2
-Achondroplasia
-Androgenic Alopecia
-Adult Polycystic Kidney Dz
-Noonan’s Syndrome
-Tuberous Sclerosis
-Hypercholesterolemia
-Huntington’s
-Hereditary Spherocytosis
-Hypertrophic Obstructive Cardiomyopathy
***MEN, FAP,
VWF
dec VWF/defect in platelet plug formation
AD
-each generation affected
-at least one parent of affected person has trait
-males ~ females
-“variable expressivity”
AD diseases
Inc BT, inc/normal PTT, normal PT
-defect in platelet plug formation/dec vwf
TX: desmospressin (ADH) analog, releases VWF from weibel palace bodies in endothelium
DX?
DZ?
Dominance?
Von Willebrand (VWF) disease
DX -abnormal Ristocetin Test- Ristocetin induces platelet agglutination by causing VWF to bind to GP1B
Dominance: AD pattern
Von Hippel Lindau disease
AD pattern
-hemangioblastomas of retina/cerebellum/medulla, bilateral renal cell carcinoma
-deletion of VHL gene (tumor suppressor) on chromosome 3
-loss of VHL gene leads to INCREASE in IGF-1 (promotes growth), and INC HIF transcription factor (inc VEGF and PDGF)
Von Hippel Lindau disease
(3 words, chromosome 3) of tumor suppressor–> so deletion of the VHL gene will lead to a bunch of tumors
AD pattern
-end organ resistance to parathyroid hormone
-“Knuckle knuckle dimple dimple”
Mechanism: G PROTEIN DEFECT
LABS: INCREASED PTH levels, HYPOCALCEMIA
(turners syndrome: knuckle knuckle dimple knuckle)
Pseudohypoparathyroidism
AD pattern
myotonia, cataracts, cardiac arrythmyias, temporal balding, “droopy face”
*UNSTABLE CTG trinucleotide REPEAT in in DMPK gene on chrom 19 or CNBP mutation on chrom 3 (type 2)
*shows anticipation
“T’s in MyoTonic DysTrophy”
Myotonic Dystrophy
AD pattern
*dont get confused with child abuse
-MC form is Type 1
-Multiple fractures, blue sclera, hearing loss, dental probs
-TYPE 1 COLLAGEN DEFECT
Osteogenesis Imperfecta
AD pattern
telangiectasia, recurrent epistaxis, skin discolorations, AV malformations (mainly mouth and GI)
mechanism: not clear
*shows anticipation
Osler Weber Rendu
(Hereditary Hemorrhagic Telangiectasia)
AD pattern
Long arms, pectus excavatum, hyper extensive joints, aortic incompetence, dissecting aortic aneurysm, upward subluxation of lens, MVP
*FIBRILLIN 1 GENE MUTATION, connective tissue disorder affecting skeleton, heart, eyes
Marfans
AD pattern
Porphobilinogen deaminase deficiency
pain in abdomen
**RED WINE COLORED URINE
TX: glucose/heme which inhibit ALA synthase
Acute intermittent porphyria
AD pattern
cafe au lait, lisch nodules,
NF1 defect on long arm of chromosome 17
NF type 1 (17 letters in this, chromosome 17)
AD pattern
Bilateral acoustic schwannomas,
NF2 defect on chromosome 22
NF type 2 (2’s go together, chromosome 22)
AD pattern
short limbs, but head and trunk are NORMAL SIZE.
A/W advanced paternal age, results in dwarfism
-defect of FGF, over expression of FGFR3= inhibits growth
types of bone:
-endochondral (cartilage matrix turns into bone–> how long bones are made) affected***
-intramembranous- (bone forms without preexisting cartilage matrix, flat bones) NOT AFFECTED HERE***
Achondroplasia
AD pattern
MC baldness in men and women
AD pattern
Androgenic Alopecia
always bilateral
hypertension (from INCREASING renin)
hematuria
**ASSOCIATED WITH Polycystic liver disease (MCC extra renal association-liver cysts)
**Berry aneurysms (MCC death)
MVP
**majority are due to PKD1 MUTATION ON CHROMOSOME 16
Adult Polycystic Kidney Disease
AD pattern
*polycystic kidney is 16 letters, PKD1 on ch 16
Male version of turners syndrome
Noonan syndrome
AD w/ variable expression
facial lesions
HYPOPIGMENTED ASH LEAF SPOTS ON SKIN
corical/retinal hematomas
seizures, retard, renal cysts
renal angiomyolipomas, cardiac rhabdomyomas, increase incidence of astrocytomas
INcomplete penetrance, variable expression
Tuberous sclerosis
AD pattern
**kid with seizures with ash leaf spots–> think tuberous sclerosis
xanthomas (tendons, classically achilles)
MI develops BEFORE AGE 20–> die
**HIGH LDL CHOLEST, TOTAL CHOL BUT NORMAL TRIGLYCERIDES
*ELEVATED LDL DUE TO DEFECT OR ABSENT LDL RECEPTOR
*if homozyotic= 700+
Hypercholesterolemia
AD pattern
depression, progressive dementia,
choreiform movements,
CAUDATE ATROPHY,
decrease levels of GABA and Ach in the brain
Associated with anticipation
***CAG trinucleotide repeat, chromosome 4
Huntington’s disease
(hunt has 4 letters, CAG)
AD pattern
**flailing arms, jerky choreiform movement
hemolytic anemia
splenomegaly
jaundice with UNCONJUG bilirubin
**INCREASE MCHC
**spectrin/ankyrin defect
-spherocytes cant navigate thru spleen and are eaten by macrophages
TX: SPLENECTOMY
Hereditary Spherocytosis
AD pattern
(giant circles purple)
SOB, but most are asymptomatic, sudden death
**mainly a DIASTOLIC problem, defect in SACROMERE proteins
**ECHO IS GOLD STAND DX
Hypertrophic Obstructive Cardiomyopathy
AD pattern
(large red heart)
**sacromere defect, sudden death in athletes
-most ENZYME deficiencies follow this pattern
-disease is in homozygotes
-more UNIFORM expression than AD
-Complete penetrance
-Onset is Early in life
-Proteins show LOSS OF FUNCTION
-Much more common than AD
Autosomal recessive
“Skips a generation”
Autosomal Recessive (14)
-Albinism
-ARPKD
-Beta Thalassemia
-Cystic fibrosis
-Deafness
-Emphysema
-Friedrich’s Ataxia
-Gaucher’s
-Galactosenmia
-Glycogen storage DZ =
-von gierke-(severe hypoglycemia)
-pompe (cardiomegaly)
-Cori
-Anderson
-McArdle (m for muscle- musclecramps)
-Hers (H for hepatic-hepatomegaly)
-Hemochromatosis
-Mucopolysaccharides/hurlers (except hunter-XR)
-Lysosomal storage diseases (except Fabry’s)
-PKU
**SCD, gilbert, crig
deficiency in TYROSINASE
impairs MELANIN production
at risk from UVB
Variable inheritance due to locus heterogeneity
Albinism
AR pattern
*Associated with congenital hepatic fibrosis
*renal failure in utero can lead to POTTER’S
*HTN
ARPKD
AR pattern
anemia due to decreased synthesis of GLOBIN CHAINS
-Hgb= heme + globin (thalassemia)
**TARGET CELLS
BETA thalassemia (target cells)
AR pattern
**(Heme= Fe + Protoporphyrin (sideroblastic))
salty taste on skin
thick VICOUS mucus
dec absorption of vitamins/enzymes
cystic fibrosis
AR pattern
deafness
AR pattern
Alpha 1 antitrypsin deficiency
Loss of elastic recoil
emphysema
AR pattern
degenerative disorder of cerebellum and spinal cord
loss of cerebellum gives ataxia
loss of multiple spinal cord tracts lose vibratory sense and DTR’s
**DUE TO EXPANSION OF UNSTABLE TRINUCLEOTIDE REPEAT GAA IN FRATAXIN GENE
**frataxin is essential for mitochondrial iron regulation
(loss results in iron buildup - free radical)
***ASSOCIATED WITH HYPERTROPHIC CARDIOMYOPATHY
Friedreich’s ataxia
AR pattern
(GAA frataxin gene mutation)
Gaucher’s (big stomach pic)
AR pattern
body is unable to process galactose (sugar present in milk)
*builds up in liver damage, brain damage, cataracts, jaundice
Galactosenmia
AR pattern
Glycogen storage diseases
1= Von Gierke (Glucose 6 phosphatase)
2= Pompe (a1, 4- glucosidase)- cardiomegaly
3= Cori (Glycogen debranching)
4= Anderson (branching enzyme)
5= McArdle (muscle glycogen phosphorylase)
6= Hers (hepatic glycogen phosphorylase)
Brown skin
Hemochromatosis
AR
group of metabolic disorders caused by absence or malfunctioning of lysosomal enzymes needed to breakdown molecules called glycosaminoglycans (GAGs)
**alpha 1 iduronidase def
**CORNEAL CLOUDING
Mucopolysaccharides/ Hurlers (except hunter -XR)
-Alpha L Iduronidase def
Lysosomal storage diseases
“Fabulous Goucho’s at Niemanns Makes Tay Krabbe”
Fabry’s (XR)
Gaucher’s (AR)
Niemann-Pick (AR)
Metachromatic Leukodystrophy (AR)
Tay Sachs (AR)
Krabbe (AR)
Tay: NO hepatosplenomegaly
Niemann- HEPATOSPLENOMEGALY
MUSTY body odor
AROMATIC AMINO ACID disorder
mental retard, growth retard
**DEC in Phenylalanine Hydroxylase, dec in tetrahydrobiopterin, tyrosine becomes essential
Inc Phenylalanine leads to INC phenylketones in urine
TX: dec phenylalanine (contained in aspartame, nutrasweet) and increase in tyrosine in diet
PKU
AR pattern
X Linked Recessive
“Be Wise, Fools GOLD Hurts High Hopes”
Bruton’s agammaglobulinemia
Wiskott Aldrich Syndrome
Fabry’s Syndrome
G6PD def
Ocular Albinism
Lesch Nyhan Syndrome
Dystrophy (duchenne’s and brecker’s)
Hunter’s Syndrome
Hemophilia A (8)
Hemophilia B (9)
disordered B cell maturation
*mutated tyrosine kinase
*presents after 6 months of life
-Recurrent bacterial, entroviral (polio, coxs), and Giardia infections
-avoid live vax
Bruton’s agammaglobulinemia
XR
Wiskott aldrich
(WAITER)
“WAITER”
WASP gene mutation
HYPER IGA, DEC IGM
dIes by Bleeding
Thrombocytopenia
Eczema
Recurrent infections
XR
Fabry’s disease
(fabry’c)
Foam cells/febrile episodes
Alpha galactosidase, A deficiency, Angiokeratomas
Burning pain hands/feet, “peripheral neuropathy”/Boys
Renal failure **THINK kidney
YX genotype (Male, x linked recessive)
Ceramide Trihexoside ACCUMULATION /CV disease
X linked Recessive
X linked recessive disorder
RBC hemolysis after exposure to oxidative drugs (aspirin, sulfa, nitro, dapsone, primaquine, quinidine), fava beans or infection
**BITE cells and HEINZ bodies
**Mediteranean descent
(oxidative drugs should be avoided)
G6PD
MORFHI BITES w/ G6PD (morph w/ F)
M: Mediterranean descent
O: oxidative drugs exposure, should be avoided
R: RBC hemolysis
P: g6Pd
F: fava beans
H: HEINZ bodies
I: infection. anemia
BITE CELS
XR
Eyes lack melanin
Skin/Hair show normal coloration
(black baby with blue eyes)
Ocular Albinism
XR
Lesch-Nyhan
“Men Suck Self Hand- LESCH”
XR
Mental retardation
Self mutilation
HGPRT
Lesch Nyhan
deletion of dystrophin gene
INC creatine kinase
Duchenne’s XR
Mutated dystrophin gene (milder form)
Becker’s XR
Hunter’s
XR
Hemophilia A / B
XR
X Linked Dominant
*at least one parent of either sex is affected and ALL female offspring of affected males have the disease
-Vitamin D/Ricketts
-Fragile X
too much CGG leads to hypermethylation and gene inactivation
*prominent/long ears
*long face, delayed speech
*large testes, macroorchidism
*autistic like behavior
Fragile X - CGG
XD
Mitochondrial Inheritance: transmitted to ALL by MOM
*during meiosis determines which offspring get a more severe or less severe version
MLL
Myoclonic epilepsy w/ ragged red fibers (MERRF)
Leigh Syndrome
Lebers Hereditary Optic Neuropathy
DOWNS
-trisomy 21 on chromosome 21, assoc with maternal age, duodenal artesia, ALL, Early alzheimer’s dementia, AB amyloid, Hirschsprung dz
DEC alpha feto protein
INC beta HCG
DEC Estriol
INC Inhibit A
meiotic non dysfunction, robertsonion translocation
DX: karyotyping of fetal cells
**if you see young kid, repeated sinus infections, ear aches, membrane potential probs in nasal/lung/sweat glands, fam hx, THICK VICOUS FLUID, absence of vas deferens
**most likely to die from respiratory infection
CYSTIC FIBROSIS, ATP GATED CHANNELS, CFTR MUTATION
sweat glands/epithelial surfaces:
CL GETS OUT (INC CL SECRETION, NA SECRETION)
lung/nasal/etc: CL CANT GET OUT (INC CL ABSORT, NA ABSORPTION), big ^^ in membrane potential diff, THICK VICOUS FLUID
DX: CHLORIDE IN THE SWEAT
TX: PANCREATIC LIPASE
achondroplasia
**homozygotes leads to death
AD
FGFR3 gene
**if you see
epicanthal folds
flattened facial profile and nose
older woman giving birth
duodenal atresia
ALL
early alzheimers
downs “down up down up”
Meiotic non disjunction: 3 copies of ch 21
if they say its not ^, then its robertsonian translocation and part of it becomes attached to another
if you see GOMORI TRICHROME stain: Mitochondrial Myopathy, mitochondrial inheritance
what % of their kids will get it
100% of children will get it if mom has it
0% of children will get it if dad has it
DEFICIENCY OF TRYPTOPHAN
***may lead to NIACIN DEFICIENCY
**ELEVATED 5HIAA SEROTONIN LEVELS IN URINE
carcinoid syndrome
HIGH unconjug bili
UGT1A1 GENE MUTATION
dec UDPGT
Gilberts
(episodic jaundice, resolves)
ABSENT UDPGT
HIGH unconj bili
early baby, death
TX: liver transplant
Crigler -Najjar
