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7/29/2019 Table of Genetic Disorders
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TABLE of GENETIC DISORDERS
Disease Category Pathogenesis / Heredity Pathology, Cardinal
Symptoms
Cystic Fibrosis Autosomal Recessive. CFTR
gene defect on Chrom 7 ------>
No Cl- transport and failure to
hydrate mucous secretions (no
NaCl transport) ------>
excessively viscous mucoid
exocrine secretions
Meconium ileus (caused by thick,
mucoid meconium), respiratory
bronchiectasis,Pseudomonas pne
umonia, pancreatic insufficiency,
hypertonic (high Cl-concentration)
sweat.
Fanconi Anemia Autosomal Recessivecongenitalpancytopenia. Normocytic anemia withneutropenia.
Short stature, microcephaly,
hypogenitalism, strabismus,
anomalies of the thumbs, radii,
and kidneys, mental retardation,
and microphthalmia.
Hartnup's
Disease
Autosomal Recessive. Defect in
GI uptake of neutral amino
acids ------> malabsorption
oftryptophan (niacin
precursor) ------> niacin
deficiency among other things.
Pellagra-like syndrome (diarrhea,
dementia, dermatitis), light-
sensitive skin rash, temporary
cerebellar ataxia.
Kartagener's
Syndrome
Autosomal Recessive. Defect
in dynein arms ------> lost
motility ofcilia
Recurrent sinopulmonary
infections (due to impaired
ciliary tract). Situs inversus,
due to impaired ciliary motion
during embryogenesis: lateral
transposition of lungs, abdominal
and thoracic viscera are on
opposite sides of the body as
normal. Possible dextrocardia,
male sterility.
PyruvateDehydrogenase
Deficiency
Autosomal Recessive.PyruvateDehydrogenasedeficiency -----
-> buildup of lactate and
pyruvate ------>lactic
acidosis.
Neurologic defects.
Treatment: Increase intake
ofketogenic nutrients (leucine,
lysine) ------> increase
formation of Acetyl-CoA from
other sources.
Xeroderma Autosomal Recessive. Defect in Dry skin, melanomas, pre-
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Pigmentosum DNA repair, inability to
repair thymine
dimers resulting from UV-
light exposure ------>
excessive skin damage and skin
cancer.
malignant lesions, other cancers.
Ophthalmic and neurologic
abnormalities.
Familial
Hypercholestero
lemia
Autosomal
Dominant
Disorders
A group of inherited diseases
associated with
hypercholestrolemia.
Heterozygous: accelerated
atherosclerosis. Homozygous:
accelerated atherosclerosis, MI by
age 35, xanthomas.
Hereditary
Hemorrhagic
Telangiectasia
(Osler-Weber-
Rendu
Syndrome)
Autosomal
Dominant
Disorders
Autosomal Dominant. Telangiectasias of skin and
mucous membranes.
Hereditary
Spherocytosis
Autosomal
DominantDisorders
Autosomal Dominant. Band-
3 deficiency in RBC membrane ------> spherical shape to cells.
Other RBC structural enzyme
deficiencies can cause it, too.
Sequestration of spherocytes in
spleen ------> hemolytic anemia.
Huntington's
Disease
Autosomal
Dominant
Disorders
Autosomal Dominant, 100%
penetrance.
Genetic defect on Chrom 4 -----
-> atrophy of caudate nuclei,
putamen, frontal cortex.
Progressive dementia with onset
in adulthood, choreiform
movements, athetosis.
Marfan's
Syndrome
Autosomal
DominantDisorders
Autosomal
Dominant.Fibrillin deficiency ------> faulty scaffolding in
connective tissue (elastin has
no anchor).
Arachnodactyly, dissecting aortic
aneurysms, ectopialentis (subluxation of lens),
mitral valve prolapse.
Neurofibromatos
is (Von
Recklinghausen
Disease)
Autosomal
Dominant
Disorders
Autosomal Dominant. NF1
gene defect (no GTPase
protein) ------> dysregulation
ofRas tumor-suppressor
protein.
Multiple neurofibromas (Caf?au
Lait spots) which may become
malignant,Lisch
nodules (pigmented
hamartomas of the iris).
Increased risk for tumors:
pheochromocytoma, Wilms
tumor, Rhabdomyosarcoma,
leukemias.
Tuberous
Sclerosis
Autosomal
Dominant
Disorders
Autosomal Dominant. Tubers (glial nodules), seizures,
mental retardation. Associated
with adenoma sebaceum (facial
lesion), myocardial
rhabdomyomas, renal
angiomyolipomas.
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Von Hippel-
Lindau
Syndrome
Autosomal
Dominant
Disorders
Autosomal Dominant, short arm
of chromosome 3. Same genetic
region is associated with
incidence ofrenal cell
carcinoma.
(1) Hemangioblastomas of
cerebellum, medulla, or retina,
(2) adenomas, (3) cysts in
visceral organs. High risk for
renal cell carcinoma.
CongenitalFructose
Intolerance
Carbohydrate
Metabolis
m Defect
Autosomal Recessive.AldolaseB deficiency ------> buildup
ofFructose-1-Phosphate in
tissues ------> inhibit
glycogenolysis and
gluconeogenesis.
Severe hypoglycemia.Treatment: Remove fructose from
diet.
Galactosemia Carbohydr
ate
Metabolis
m Defect
Autosomal Recessive. Inability
to convert galactose to glucose
------> accumulation of
galactose in many tissues.
(1) Classic form: Galactose-1-
phosphate
Uridyltransferasedeficiency.
(2) Rarer
form:Galactokinase deficiency.
Failure to thrive, infantile
cataracts, mental retardation.
Progressive hepatic
failure, cirrhosis, death.
Galactokinase-deficiency:
infantile cataracts are prominent.
Treatment: in either case,remove
galactose from diet.
Angelman
Syndrome
Chromoso
mal
Deletion of part of short arm
ofchromosome 15, maternal
copy. An example ofgenomic
imprinting.
Mental retardation, ataxic gait,
seizures.Inappropriate
laughter.
Cri du Chat
Syndrome
Chromoso
mal
5p-, deletion of the long arm of
chromosome 5.
"Cry of the cat." Severe mental
retardation, microcephaly, cat-
like cry. Low birth-weight, round-
face, hypertelorism (wide-seteyes), low-set ears, epicanthal
folds.
Down Syndrome
(Trisomy 21)
Chromoso
mal
Trisomy 21, with risk
increasing with maternal age.
Familial form (no age-
associated risk) is
translocation t(21,x) in a
minority of cases.
Most common cause of mental
retardation. Will see epicanthal
folds, simian
crease, brushfield spots in
eyes. Associated
syndromes: congenital heart
disease, leukemia,premature
Alzheimer's disease (same
morphological changes).
Edward'sSyndrome
(Trisomy 18)
Chromosomal
Trisomy 18 Mental retardation,micrognathia, rocker-bottom
feet, congenital heart disease,
flexion deformities of fingers.
Death by 1 year old.
Patau's
Syndrome
Chromoso
mal
Trisomy 13 Mental retardation,
microphthalmia, cleft lip and
palate, polydactyly, rocker-
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(Trisomy 13)
bottom feet, congenital heart
disease. Similar to and more
severe than Edward's Syndrome.
Death by 1 year old.
Prader-Willi
Syndrome
Chromoso
mal
Deletion of part of short arm
ofchromosome 15, paternalcopy. An example ofgenomic
imprinting.
Mental retardation, short stature,
hypotonia, obesity and hugeappetite after infancy. Small
hands and feet, hypogonadism.
Fragile-X
Syndrome
Chromoso
mal
Sex
chromoso
me
Progressively longertandem
repeats on the long arm of the
X-chromosome. The longer the
number of repeats, the worse
the syndrome. Tandem repeats
tend to accumulate through
generations.
Second most common cause
ofmental retardation next to
Down Syndrome. Macro-
orchidism (enlarged testes) in
males.
Klinefelter's
Syndrome (XXY)
Chromoso
mal
Sex
chromoso
me
Non-disjunction of the sex
chromosome during Anaphase I
of meiosis ------> Trisomy(47,XXY)
Hypogonadism, tall stature,
gynecomastia. Mild mental
retardation. Usually notdiagnosed until after puberty.
One Barr body seen on buccal
smear.
Turner's
Syndrome (XO)
Chromoso
mal
Sex
chromoso
me
Non-disjunction of the sex
chromosome during Anaphase I
of meiosis ------> Monosomy
(45,X)
Streak gonads, primary
amenorrhea, webbed neck, short
stature, coarctation of Aorta,
infantile genitalia.No mental
retardation. No Barr bodies
visible on buccal smear.
XXX Syndrome Chromoso
mal
Sex
chromoso
me
Trisomy (47,XXX) and other
multiple X-chromosomeabnormalities.
Usually phenotypically normal.
May see menstrual abnormalitiesor mild mental retardation in
some cases.
Ehlers-Danlos
Syndrome
Connectiv
e Tissue
disease
Various defects in collagen
synthesis.
Type-I: Autosomaldominant, mildest form.
Type-IV: autosomaldominant. Defect in
reticular collagen (type-III)
Type-VI: autosomal-recessive.
Type-VII: Defect incollagen type I
Type-IX: X-linkedrecessive
Laxity of joints, hyperextensibility
of skin, poor wound healing,
aneurysms.
Type-I: Diaphragmatichernia. Common, normal
life-expectancy.
Type-IV: Ecchymoses,arterial
rupture. Dangerousdue to
rupture aneurysms.
Type-VI: Retinaldetachment, corneal
rupture
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Osteogenesis
Imperfecta
Connectiv
e tissue
disease
Defects in Collagen Type
Iformation.
Multiple fractures after
birth, blue sclerae, thin skin,
progressive deafness in some
types (due to abnormal middle
ear ossicles).
Type-I is most common;Type-II is most severe;Type-IV is
mildest form.
Cori's Disease
(Glycogen
Storage Disease
Type III)
Glycogen
Storage
Disease
Autosomal
Recessive.Debranching
enzymedeficiency (can only
break down linear chains of
glycogen, not at branch points)
------> accumulate glycogen in
liver, heart, skeletal muscle.
Stunted growth, hepatomegaly,
hypoglycemia.
McArdle's
Disease
(Glycogen
Storage Disease
Type V)
Glycogen
Storage
Disease
Autosomal Recessive.muscle
phosphorylasedeficiency
(cannot utilize glycogen in
skeletal muscle) ------>
accumulation of glycogen in
skeletal muscle.
Muscle cramps, muscle
weakness, easy fatigability.
Myoglobinuria with strenuous
exercise.
Pompe's Disease
(Glycogen
Storage Disease
Type II)
Glycogen
Storage
Disease
Autosomal Recessive.alpha-
1,4-Glucosidasedeficiency
(cannot break down glycogen) -
-----> accumulate glycogen in
liver, heart, skeletal muscle.
Cardiomegaly, hepatomegaly,
and systemic findings, leading to
early death.
Von Gierke's
Disease
(Glycogen
Storage Disease
Type I)
Glycogen
Storage
Disease
Autosomal Recessive.Glucose-
6-Phosphatasedeficiency
(cannot break down glycogen) ------> accumulate glycogen in
liver and kidney.
Severe fastinghypoglycemia,
hepatomegaly from lots of
glycogen in liver.
Hemophilia A
(Factor VIII
Deficiency)
Hemophili
a
X-Linked Recessive. Factor
VIII deficiency
Hemorrhage, hematuria,
hemarthroses. Prolonged PTT.
Hemophilia B
(Factor IX
Deficiency)
Hemophili
a
X-Linked Recessive. Factor
IX deficiency.
Milder than Hemophilia A.
Hemorrhage, hematuria,
hemarthroses. Prolonged PTT.
Von WillebrandDisease Hemophilia Autosomal dominant andrecessive varieties. Von
Willebrand Factordeficiency --
----> defect in initial formation
of platelet plugs, and shorter
half-life of Factor VIII in blood.
Hemorrhage, similar tohemophilia.
Type-I: Most mild. Type-II:
Intermediate. Type-III: most
severe, with recessive inheritance
(complete absence).
Ataxia- Immune Autosomal Recessive. Unknown. Cerebellar ataxia, telangiectasia
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Telangiectasia deficiency
Combined
Deficiency
Numerous chromosomal breaks
and elevated AFP is found.
Symptomatic by age 2 years.
(enlarged capillaries of face and
skin),B and T-Cell deficiencies,
IgA deficiency.
Ch?iak-Higashi
Syndrome
Immune
deficiency
Phagocyte
Deficiency
Defect in polymerization of
microtubules in neutrophils ------> failure
in neutrophilmigration and
phagocytosis. Also results in
failure in lysosomal
function in neutrophils.
Recurrent pyogenic
infections, Staphylococcus,Streptococcus.
Chronic
Granulomatous
Disease
Immune
deficiency
Phagocyte
Deficiency
X-Linked (usually) NADPH
Oxidase deficiency ------> no
formation of peroxides and
superoxides ------> no oxidative
burst in phagocytes.
Failure of phagocytes leads to
susceptibility to infections,
especially Staph
Aureus andAspergillus spp. B
and T cells usually remain
normal.
Chronic
Mucocutaneous
Candidiasis
Immune
deficiency
T-Cell
Deficiency
T-Cell deficiency specific
toCandida.
Selective
recurrent Candidainfections.
Treat with anti-fungal drugs.
Job's Syndrome Immune
deficiency
Phagocyte
Deficiency
A failure to producegamma-
Interferon by T-Helper cells,
leading to an increase in TH2
cells (no negative feedback) ----
--> excessively high levels
ofIgE.
High histamine levels,
eosinophilia. Recurrent cold(non-
inflammatory)
Staphylococcal abscesses(resulti
ng from high histamine), eczema.
Selective IgADeficiency
Immunedeficiency
B-Cell
Deficiency
IgA deficiency may be due to afailure of heavy-chain gene
switching.
The most common congenitalimmune deficiency. There also
exists selective IgM and IgG
deficiencies, but they are less
common.
Severe
Combined
Immunodeficien
cy (SCID)
Immune
deficiency
Combined
Deficiency
Autosomal
Recessive.Adenosine
Deaminasedeficiency ------>
accumulation ofdATP ------>
inhibit ribonucleotide reductase
------> decrease in DNA
precursors
Severe deficiency in both humoral
and cellular immunity, due to
impaired DNA synthesis. Bone
marrow transplant may be helpful
in treatment.
Thymic Aplasia
(DiGeorge
Syndrome)
Immune
deficiency
T-Cell
Deficiency
Failure of development of
the 3rd and 4thPharyngeal
Pouches ------> agenesis of
the thymus and parathyroid
glands.
T-Cell deficiency from no
thymus. Hypocalcemic
tetany from primary parathyroid
deficiency.
Wiskott-Aldrich
Syndrome
Immune
deficiency
Inability to mount
initial IgMresponse to the
capsular polysaccharides of
In infancy, recurrent pyogenic
infections, eczema,
thrombocytopenia, excessive
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Combined
Deficiency
pyogenic bacteria. bleeding. IgG levels remain
normal.
X-Linked
Agammaglobulin
emia (Bruton'sDisease)
Immune
deficiency
B-Cell
Deficiency
X-Linked. Mutation in gene
coding for tyrosine
kinasecauses failure of Pre-Bcells to differentiate into B-
Cells.
Recurrent pyogenic infections
after 6 months (when maternal
antibodies wear off). Can treatwith polyspecific gamma globulin
preparations.
Fabry's Disease Lysosomal
Storage
Disease
X-Linked Recessive. alpha-
Galactosidase A deficiency ----
--> buildup ofceramide
trihexoside in body tissues.
Angiokeratomas (skin lesions)
over lower trunk, fever, severe
burning pain in extremities,
cardiovascular and
cerebrovascular involvement.
Gaucher's
Disease
Lysosomal
Storage
Disease
Autosomal
Recessive.Glucocerebrosidase
deficiency ------> accumulation
of glucocerebrosides(gangliosides, sphingolipids) in
lysosomes throughout the body.
Type-I: Adult form. 80%of cases, retain partial
activity.
Hepatosplenomegaly,erosion of femoral head,
mildanemia. Normal
lifespan with treatment.
Type-II: Infantile form.Severe CNS involvement.
Death before age 1.
Type-III: Juvenile form.Onset in early childhood,
involving both CNS and
viscera, but less severe
than Type II.
Niemann-Pick
Lipidosis
Lysosomal
Storage
Disease
Autosomal
Recessive.Sphingomyelinased
eficiency ------> accumulation
of sphingomyelin in phagocytes.
Sphingomyelin-containingfoamy
histiocytes in reticuloendo-
thelial system and spleen.
Hepatosplenomegaly,anemia,
fever, sometimes CNS
deterioration. Death by age 3.
Hunter's
Syndrome
Lysosomal
Storage
Disease
X-Linked Recessive. L-
iduronosulfate
sulfatasedeficiency ------>
buildup
ofmucopolysaccharides(hepar
an sulfate and dermatan
sulfate)
Similar to but less severe than
Hurler Syndrome.
Hepatosplenomegaly,
micrognathia, retinal
degeneration, joint stiffness, mild
retardation, cardiac lesions.
Hurler's
Syndrome
Lysosomal
Storage
Disease
Autosomal Recessive.alpha-L-
iduronidasedeficiency ------>
accumulation
ofmucopolysaccharides(hepar
an sulfate, dermatan sulfate) in
heart, brain, liver, other organs.
Gargoyle-like facies, progressive
mental deterioration, stubby
fingers, death by age 10. Similar
to Hunter's Syndrome.
Tay-Sachs Lysosomal Autosomal CNS degeneration,
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Disease Storage
Disease
Recessive.Hexosaminidase
Adeficiency ------>
accumulation of GM2ganglioside
in neurons.
retardation, cherry red-spot of
macula, blindness (amaurosis).
Death before age 4.
Albinism Nitrogen
Metabolism Defect
Autosomal
Recessive.Tyrosinase deficiency ------> inability to synthesize
melanin from tyrosine. Can
result from a lack of migration
of neural crest cells.
Depigmentation, pink eyes,
increased risk of skin cancer.
Alkaptonuria Nitrogen
Metabolis
m Defect
Autosomal
Recessive.Homogentisic
Oxidasedeficiency (inability to
metabolize Phe and Tyr) ------>
buildup and urinary excretion
ofhomogentisic acid.
Urine turns dark and black on
standing, ochronosis(dark
pigmentation of fibrous and
cartilage tissues), ochronotic
arthritis, cardiac valve
involvement. Disease is
generally benign.
Homocystinuria NitrogenMetabolis
m Defect
AutosomalRecessive.Cystathionine
synthasedefect (either
deficiency, or lost affinity for
pyridoxine, Vit. B6) ------>
buildup of homocystine and
deficiency of cysteine.
Mental retardation, ectopia lentis,sparse blond hair, genu valgum,
failure to thrive, thromboembolic
episodes, fatty changes of liver.
Treatment: Cysteine
supplementation, give excess
pyridoxine to compensate for lost
pyridoxine affinity.
Lesch-Nyhan
Syndrome
Nitrogen
Metabolis
m Defect
X-Linked
Recessive.Hypoxanthine-
Guanine
Phosphoribosyltransferase(HGPRT) deficiency ------> no
salvage pathway for purine re-
synthesis ------> buildup of
purine metabolites
Hyperuricemia (gout), mental
retardation, self-mutilation
(autistic behavior),
choreoathetosis, spasticity.
Maple Syrup
Urine Disease
Nitrogen
Metabolis
m Defect
Autosomal Recessive. Deficiency
ofbranched chain keto-acid
decarboxylase ------> no
degradation of branched-chain
amino acids ------> buildup
ofisoleucine, valine, leucine.
Severe CNS defects, mental
retardation, death. Person smells
like maple syrup or burnt sugar.
Treatment:remove the amino
acids from diet.
Phenylketonuria
(PKU)
Nitrogen
Metabolism Defect
Autosomal
Recessive.Phenylalaninehydroxylase deficiency (cannot
break down Phe nor make Tyr)
------> buildup of
phenylalanine, phenyl ketones
(phenylacetate, phenyl lactate,
phenylpyruvate) in body tissues
and CNS.
Symptoms result from
accumulation of phenylalanineitself. Mental deterioration,
hypopigmentation (blond hair and
blue eyes), mousy body odor
(from phenylacetic acid in urine
and sweat).
Treatment: remove phenylalanine
from diet.
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Glucose-6-
Phosphate
Dehydrogenase
(G6PD)
Deficiency
RBC
Disease
X-Linked Recessive.Glucose-6-
Phosphate Dehydrogenase
(G6PD)deficiency ------> no
hexose monophosphate shunt --
----> deficiency in NADPH ------
> inability to
maintainglutathione inreduced form, in RBC's
Susceptibility to oxidative
damage to RBC's, leading
to hemolytic anemia. Can be
elicited by drugs (primaquine,
sulfonamides, aspirin), fava
beans (favism). More prevalent
in blacks.
Glycolytic
enzyme
deficiencies
RBC
Disease
Autosomal Recessive. Defect in
hexokinase, glucose-phosphate
isomerase, aldolase, triose-
phosphate isomerase,
phosphate-glycerate kinase, or
enolase. Any enzyme in
glycolysis pathway.
Hemolytic anemia results from
any defect in the glycolysis
pathway, as RBC's depend on
glycolysis for energy.
Autosomal
Recessive
Polycystic
Kidney Disease(ARPKD)
Renal Autosomal Recessive. Numerous, diffuse bilateral cysts
formed in the collecting ducts.
Associated with hepatic fibrosis.
Bartter's
Syndrome
Renal Juxtaglomerular Cell
Hyperplasia, leading toprimary
hyper-reninemia.
Elevated renin and aldosterone,
hypokalemic alkalosis. No
hypertension.
Fanconi's
Syndrome Type
I
(Child-onset
cystinosis)
Renal Autosomal Recessive. Deficient
resorption in proximal tubules.
(1) Cystine deposition throughout
body, cystinuria. (2) Defective
tubular resorption leads to
amino-aciduria, polyuria,
glycosuria, chronic
acidosis;Hypophosphatemia an
dVitamin-D-resistant Rickets.
Fanconi's
Syndrome II
(Adult-onset)
Renal Autosomal Recessive. Defective
resorption in proximal tubules.
Similar to Fanconi Syndrome
Type I, but without the
cystinosis. Adult
onsetosteomalacia, amino-
aciduria, polyuria, glycosuria.
Autosomal
Dominant
Polycystic
Kidney Disease
(ADPKD)
Renal
Autosomal
Dominant
Disorders
Autosomal Dominant. Numerous, disparate,
heterogenous renal cysts
occurring bilaterally. Onset in
adult life. Associated with liver
cysts.
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Front
Back
Prader-Willi Syndrome
Chr: 15Mx: Inactivation/deletion/uniparental disomy.Imprinting. Deletion of active paternal allele.Hx: Mental retardation, hyperphagia, obesity,hypogonadism, hypotonia.
Angelman Syndrome
Chr: 15Mx: Inactivation/deletion/uniparental disomy.Imprinting. Deletion of active maternal allele.Hx: Mental retardation, seizures, ataxia, inappropriatelaughter ("happy puppet").
Achondroplasia
Gn: FGFR3Mx: ADFx: Cell-signaling defectHx: Dwarfism, short limbs, head+trunk same size.Assoc: Adv. paternal age.
Autosomal-Dominant Polycystic Kidney Disease
Chr: 16Gn: APKD1 (point mutation)Fx: Always bilateral massive kidney enlargement ofkidneys due to multiple large cysts.Onset: AdultHx: Flank pain, hematuria, HTN, progressive renalfailure.
Assoc: Polycystic liver dz, berry aneurysms, mitralvalve prolapse.
Familial Adenomatous Polyposis
Chr: 5Gn: APC (deletion)Mx: ADFx: Colon covered with adenomatous polyps afterpuberty, always progresses to colon CA unlessresected.
Familial Hypercholesterolemia (HLE IIA)
Gn: LDLRMx: AD
Fx: Hetero - 300 mg/dL, homo - 700+.Hx: Severe atherosclerotic dz early in life, tendonxanthomas (Achilles), MI < 20 y/o.
Hereditary Hemorrhagic Telangiectasia (Osler-Weber-Rendu)
Mx: ADFx: Inherited disorder of blood vesselsHx: Telangiectasia, epistaxis, skin discolorations,AVMs.
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Hereditary Spherocytosis
Mx: ADGn: Spectrin/Ankyrin defectFx: Spheroid erythrocytesHx: Hemolytic anemia, MCHCTx: Splenectomy
Huntington's Disease
Chr: 4Mx: AD, CAC-repeatHx: Depression, progressive dementia, choreiformmovements, caudate atrophy, GABA+ACh. S/S 20-50y/o.
Marfan's Syndrome
Gen: FibrillinMx: ADHx: Tall w/long extremities, pectus excavatum,hyperextensive joints, arachnodactyly, aortic cysticmedial necrosisaortic dissection, floppy mitral valve,lens subluxation.
Multiple Endocrine Neoplasia 1Mx: ADHx: Pancreas+Parathyroid+Pituitary
Multiple Endocrine Neoplasia 2Mx: ADGen: RetHx: Thyroid+Medulla
Neurofibromatosis 1 (von Recklinghausen's
Disease)
Chr: 17qMx: ADGen: NF1Hx: Cafe-au-lait spots, neural tumors, Lisch nodules(pigmented iris hamartomas).Assoc: Skeletal disorders (e.g., scoliosis), opticgliomas, pheochromocytomas, tumors.
Neurofibromatosis 2
ChrMx: ADGen: NF2Hx: Bilateral acoustic neuroma, juvenile cataracts.
Tuberous sclerosis
Mx: AD (incomplete penetrance, variable presentation)Hx: Facial lesions (adenoma sebaceum),hypopigmented "ash leaf spots" on skin,cortical+retinal hamartomas, seizures, mentalretardation, renal cysts+angiomyolipomas, cardiacrhabdomyomas, astrocytomas.
von Hippel-Lindau Disease
Chr: 3pMx: AD, deletion.Gen: VHL (tumor suppressor)Fx: Constituitive HIF (transcription factor) expression,
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angiogenic growth factor activation.Hx: Hemangioblastomas (retina/cerebellum/medulla),bilateral renal cell carcinoma, other tumors.
Orotic Aciduria
Mx: AR
Gn: Orotic acid phosphoribosyltransferase or orotidine5'-phosphate decarboxylase
Fx: Orotic acidUMPHx: orotic acid in urine, megaloblastic anemia(B12/folate no help), failure to thrive, no NH4.Tx: PO uridine
Adenosine Deaminase DeficiencyGn: Adenosine deaminaseFx: Purine salvage deficiency, no lymphocytes.Hx: SCID.
Lesch-Nyhan Syndrome
Mx: XR
Gn: HGPRTFx: Purine salvage deficiency,
HypoxanthineIMP/GuanineGMP, uric acidHx: Retardation, self-mutilation, aggression,hyperuricemia, gout, choreoathetosis.
I-Cell Disease
Fx: Lysosomal storage disorder, can't add mannose-6-phosphate to proteins, lysosomal proteins exportedoutside cell, inclusions.Hx: Coarse facial features, clouded corneas, restrictedjoint movement, high plasma levels of lysosomalenzymes. Fatal in childhood.
Chediak-Higashi SyndromeFx: Microtubule polymerization defect, phagocytosis.Hx: Recurrent pyogenic infections, partial albinism,peripheral neuropathy.
Kartagener's Syndrome
Gn: DyneinFx: Immotile cilia, dynein arm defect.Hx: Male/female infertility, bronchiectasis, sinusitis.Assoc: Situs inversus.
Ehlers-Danlos Syndrome
Gn: COL3Fx: Faulty collagen synth.Hx: Hyperextensible skin, easy bruising/bleeding,hypermobile joints.Assoc: Joint disloc, berry aneurysms, organ rupture.
Osteogenesis Imperfecta
Mx: AD (common)Gn: COL1Hx: Multiple fractures w/minimal trauma, blue sclerae,hearing loss (abnormal middle-ear bones), dentalimperfections.
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Alport's Syndrome
Mx: XRGn: COL4Hx: Progressive hereditary nephritis, deafness, oculardisturbances.
Cystic Fibrosis
Chr: 7Mx: ARGn: CFTR (d508F)abnormal foldingdegradationbefore surfaceFx: CFTR is active chloride pump, secretes in lungs,reabsorbs from sweat. Secreton of abnormally thickmucus (lungs, pancreas, liver).Hx: Recurrent pulm infections (Pseudomonas, S.aureus), chronic bronchitis, bronchiectasis, pancreaticinsuf. (malabsorption, steatorrhea), meconium ileus,male infertility (vas deferens absent), ADEK-deficiency.Assoc: Sweat testTx: N-acetylcysteine to loosen plugs.
Duchenne's Muscular Dystrophy
Mx: XRGn: DMD (frameshift), high rate of spontaneousmutation.Fx: Accelerated muscle breakdown (dystrophinanchors fibers).Hx: Progressive weakness, start in pelvic girdle, goesup. Pseudohypertrophy of calf muscles (fibrofattyreplacement), cardiac myopathy. Onset < 5 y/o. Needarms to stand (Gowers' maneuver).Dx: CPK, biopsy.
Becker's Muscular Dystrophy
Mx: XRGn: DMDHx: Less severe than Duchenne's. Onset in adol/earlyadult. Hx: Progressive weakness, start in pelvic girdle,goes up. Pseudohypertrophy of calf muscles (fibrofattyreplacement), cardiac myopathy. Need arms to stand(Gowers' maneuver).Dx: CPK, biopsy.
Fragile X Syndrome
Mx: XRGn: FMR1 (CGG repeat)Hx: Retardation (2nd after Down), macro-orchidism,long face w/large jaw, large everted ears, autism,
mitral valve prolapse.Assoc: Chromosomal breakage
Down's Syndrome
Mx: Trisomy 21Hx: Retardation, flat facies, epicanthal folds, simiancrease, 1st 2 toes gap, duodenal atresia, septumprimum ASD.Assoc: ALL, Alzheimer's.
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Dx: Pregnancy quad screen - AFP, estriol, b-hCG,inhibin A. Nuchal translucency in usound.
Edwards' SyndromeMx: Trisomy 18Hx: Severe retardation, micrognathia, clenched hands,
heart dz.
Patau's SyndromeMx: Trisomy 13Hx: Cleft lip/palate, holoprosencephaly, polydactyly,heart dz.
Cri-du-chat SyndromeMx: 5p-Hx: Microcephaly, retardation, high-pitched cry,epicanthal folds, cardiac problems.
Williams SyndromeMx: 7q- (esp. elastin)Hx: Elfin facies, retardation, [Ca] (vitD sens), good
talker, very friendly, cardiovascular problems.
DiGeorge Syndrome
Mx: 22q11-Fx: CATCH-22: Cleft palate, Abnormal facies, Thymicaplasia, Cardiac defects, Hypocalcemia (parathyroidaplasia). Aberrant development of 3rd/4th branchialpouches.Hx: Thymic, parathyroid, cardiac defects.
Velocardiofacial Syndrome
Mx: 22q11-Fx: CATCH-22: Cleft palate, Abnormal facies, Thymicaplasia, Cardiac defects, Hypocalcemia (parathyroid
aplasia). Aberrant development of 3rd/4th branchialpouches.Hx: Palate, facial, cardiac defects.
G6PD Deficiency
Mx: XRFx: NADPHGlutathioneHemolysis.Hx: Blacks, malarial resistanceAssoc: Heinz bodies (oxidized hemoglobin), Bite cells(phagocytic removal of Heinz bodies)
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