DOMINANCE PATTERNS Flashcards by Alexis McKay

Gaucher’s disease

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NF type I

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Rett syndrome

X linked dominant

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Marfan

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myoclonic epilepsy with red ragged fibers

Mitochondiral

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Gilbert’s

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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,

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VWF
dec VWF/defect in platelet plug formation

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-each generation affected
-at least one parent of affected person has trait
-males ~ females
-“variable expressivity”

AD diseases

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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

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Von Hippel Lindau disease

AD pattern

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-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

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-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

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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

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*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

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telangiectasia, recurrent epistaxis, skin discolorations, AV malformations (mainly mouth and GI)
mechanism: not clear
*shows anticipation

Osler Weber Rendu
(Hereditary Hemorrhagic Telangiectasia)
AD pattern

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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

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Porphobilinogen deaminase deficiency
pain in abdomen
**RED WINE COLORED URINE

TX: glucose/heme which inhibit ALA synthase

Acute intermittent porphyria
AD pattern

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cafe au lait, lisch nodules,
NF1 defect on long arm of chromosome 17

NF type 1 (17 letters in this, chromosome 17)
AD pattern

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Bilateral acoustic schwannomas,
NF2 defect on chromosome 22

NF type 2 (2’s go together, chromosome 22)
AD pattern

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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

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MC baldness in men and women
AD pattern

Androgenic Alopecia

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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

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Male version of turners syndrome

Noonan syndrome
AD w/ variable expression

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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

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

Hemophilia A / B

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