table of genetic disorders

7/29/2019 Table of Genetic Disorders

1/14

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-
http://www.doctorslounge.com/gastroenterology/diagnosis/diarrhea/index.htmhttp://www.doctorslounge.com/gastroenterology/diagnosis/diarrhea/index.htmhttp://www.doctorslounge.com/gastroenterology/diagnosis/diarrhea/index.htmhttp://www.doctorslounge.com/gastroenterology/diagnosis/diarrhea/index.htm


2/14

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.


3/14

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-


4/14

(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


5/14

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


6/14

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


7/14

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,
http://d/My%20web/thedoctorslounge/clinlounge/diagnosis/anemia/index.htmhttp://d/My%20web/thedoctorslounge/clinlounge/diagnosis/anemia/index.htmhttp://d/My%20web/thedoctorslounge/clinlounge/diagnosis/anemia/index.htmhttp://d/My%20web/thedoctorslounge/clinlounge/diagnosis/anemia/index.htmhttp://d/My%20web/thedoctorslounge/clinlounge/diagnosis/anemia/index.htmhttp://d/My%20web/thedoctorslounge/clinlounge/diagnosis/anemia/index.htmhttp://d/My%20web/thedoctorslounge/clinlounge/diagnosis/anemia/index.htmhttp://d/My%20web/thedoctorslounge/clinlounge/diagnosis/anemia/index.htm


8/14

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.


9/14

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.

http://www.doctorslounge.com/studlounge/downdirty/genetic.htm
http://www.doctorslounge.com/studlounge/downdirty/genetic.htmhttp://www.doctorslounge.com/studlounge/downdirty/genetic.htmhttp://www.doctorslounge.com/studlounge/downdirty/genetic.htm


10/14

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.


11/14

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,


12/14

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.


13/14

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.


14/14

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)

http://www.flashcardexchange.com/cards/usmle-step-1-genetic-diseases-1697961
http://www.flashcardexchange.com/cards/usmle-step-1-genetic-diseases-1697961http://www.flashcardexchange.com/cards/usmle-step-1-genetic-diseases-1697961http://www.flashcardexchange.com/cards/usmle-step-1-genetic-diseases-1697961

table of genetic disorders

Documents