Genetic Disorders 1

gsafsaf's version from 2015-05-22 18:15

Extra Chromosome

Question Answer
MC TrisomyTrisomy 21 (Down's): 1/700
Flat facies, Prominent epicanthal folds, Single palmar crease, Intellectual disabilityTrisomy 21
Duodenal atresiaTrisomy 21
Endocardial cushion defect: ASD, VSDTrisomy 21
ALL (and AML)Trisomy 21 [All fall Down]
Alzheimer'sTrisomy 21
PolycythemiaTrisomy 21
MC congenital cause of intellectual disability?Trisomy 21
2MC congenital cause of intellectual disability?Fragile X
MC overall cause of intellectual disability?Fetal Alcohol syndrome
Quad: Low AFP, Low Estriol, High hCG, High InhibinTrisomy 21
Increased nuchal translucency on UltrasoundTrisomy 21, Trisomy 13, Turner's
95% cause of Down syndromeNondisjunction of homologous chromosomes
Risk factors for Trisomy 21Advanced maternal age
MosaicismTrisomy 21
5% cause of DownsyndromeRobertsonian Translocation: Extra long arm from 2 fused chromosomes... 2nd generation at risk for Down's
Rocker bottom feet, Micrognathia, Low Ears, Clenched handsTrisomy 18 [Edwards syndrome]
Low hCG, Low AFP, Low estriol, Normal inhibinTrisomy 18 [Edwards syndrome]
Death within 1 yearTrisomy 18 [Edwards syndrome] and Trisomy 13 [Patau]
Rocker- bottom feet, Microphthalmia, microcephaly, cleft liP/Palate, holoProsencephaly, Polydactyly, congenital heart disease, cutis aplasiaTrisomy 13 [Patau]
Low hCG, low PAPP-ATrisomy 13 [Patau]

Missing Chromosome

Question Answer
High pitched crying (mewing), Microcephaly, Moderate intellectual disability, Epicanthal folds, Cardiac Abnormalities (VSD)Cri du Chat
Mutation in Cri du ChatMicrodeletion of short arm of chromosome 5 (35,XX or XY, 5p-)
Elfin facies, Intillectual disability, Hypercalcemia, Verbal skills, Extreme friendliness, CV problemsWilliams syndrome [Will Ferrel in Elf]
Mutation in Williams syndromeMicrodeletion of Long arm of chromosom 7
What specific gene is deleted in WIllaims syndrome?Elastin gene
Cleft lip, Abnormal faces, Thymic aplasia (T-cell deficiency...recurrent infxn), Cardiac defects, HypocalcemiaDiGeorges [CATCH-22]
Deletion of DiGeorges?Microdeletion at chromosome 22q11
What fails to develop in DiGeorges?3rd and 4th Branchial Pouches

What Chromosome went wrong?

Question Answer
3von Hippel-Lindau disease, renal cell carcinoma
4ADPKD with PKD2 defect, Huntington
5Cri-du-chat, FAP
7Williams syndrome, CF
9Friedreich ataxia
11Wilms tumor
13Patau syndrome, wilson disease
15prader-willie, angelman
16ADPKD with PKD2 defect
17 Neurofibromatosis I
18 Edwards syndrome
21Downs syndrome
22Neurofibromatosis 2, DiGeorge syndrome (22q11)
X Fragile X, X linked agammaglobulinemia, Klinefelters (XXY)

Autosomnal Dominant Diseases

Question Answer
Flank pain, Hematuria, Hypertension, UTIADPKD
Associated with MVP, Liver disease, Berry aneurysmsADPKD
Growth pattern with ADPKD ?Bilateral enlargement of kidneys with large cysts
Neural tumors and pigmented iris HamartomasNeurofibromatosis Type 1
Colon cancerFAP
MI before 20Familial Hypercholesterolemia
Hemangioblastomas of retina/cerebellum/medullaVHL
Increased MCHC with hemolytic anemiaHereditary spherocytosis
Bilateral acoustic schwanomasNeurofibromatosis Type 2 [2=bilateral]
Facial lesions, Seizures, Cancer riskTuberous sclerosis
Cystic medial necrosis of aortaMarfan's
Associated with Berry aneurysmADPKD, Marfan's, Ehlers Danlos
Osteomas, Lipomas, Sebaceous cysts, Colon polyps and CancerGardner
Yellow deposits in eye and tendonFamilal hypercholesterolemia
Telangiectasias, Epistaxis and HematuriaHereditary Hemorrhagic Telangiectasia
Fatigue, JaundiceHereditary Spherocytosis
Subluxation of lensMarfan's
Yellow-Brown pigments in the EyeNeurofibromatosis Type 1
Bilateral hearing loss, Impaired vision, Hyperpigmented skin lesionsNeurofibromatosis type 2
Hyperpigmented skin lesionsNeurofibromatosis [Type 1: Iris Hamartomas, Type 2: Bilateral Hearing loss]
Hypopigmented skin spotsTuberous sclerosis: ash leaf spots
Multiple benign hamartomas + Systemic symptomsTuberous sclerosis
Tumors in multiple organ systemsVon Hippel LIndau


Question Answer
Mutation with ADPKD?PKD1 (Chromosome 16) or PKD2
Where can cysts spread to with ADPKD?Liver
Defect with achondroplasia?FGFR3
Risk for achondroplasiaAdvanced paternal age
Mutation with FAP?APC: 5q chromosome
Polyps covering colon after pubertyFamilial Adenomatous Polyposis ... can progress to colon cancer
Mutation in APC geneFamilial Adenomatous Polyposis (FAP), Gardner syndrome
Familial HypercholesterolemiaType IIa Hyperlipidemia
Findings in Familial HypercholesteroemiaEarly-onset MI, Tendon xanthomas, Xanthelemas
Defect in Familial hypercholesterolemia?Absent or Defective LDL Receptor!
Elevated lab finding in Familial Hyperlipidemia?LDL > 700
Inherited Disorder of blood vesselsHereditary hemorrhagic telangiectasia aka Osler-Weber Rendu
Findings in Hereditary Hemorrhagic TelangiectasiaTelangiectasias, epistaxis, skin discolorations, AVMs, GI bleed, hematuria
Labs with Hereditary spherocytosis?HgB 8.1, HighMCV, High MCHC, (+) Osmotic fragility test
Defect in Hereditary SpherocytosisSpectrin or ankyrin defect
Findings in Huntingon'sDepression, Cognitive decline, Choreiform movements, and Caudate atrophy
Low AChHuntingtons'
Complications of Marfan'sCystic medial necrosis of aorta: Aortic regurg, Aortic aneurysm, Aortic dissection
MEN1Pituitary adenomas, Parathyroid adenoma, Pancreatic tumors [PPP]
MEN2aMedullary thyroid carcinoma, Parathyroid adenoma, Pheochromocytoma [MPP]
MEN2bMedullary thyroid carcinoma, Mucosal tumors, Pheochromocytoma
RET geneMEN1 and MEN3
Mutation on chromosome 17Neurofibromatosis Type 1
Neurofibromatosis type 1 aka Von RecklinghausenCafe au lait spots, Neural tumors, Lesch nodules (pigmented iris Hamartomas)
Gene mutation with Neurofibromatosis Type 1NF1 gene, chromosome 17 [17 letters in von recklinghausen]
Mutation associated with Neurofibromatosis type 2?NF2 gene on chromosome 22 [type 2=22]
Neurofibromatosis type 2BILATERAL acoustic schwannomas, cataracts, meningiomas, and ependymomas
Findings with Tuberous sclerosisAdenoma sebaceum, Cortical and retinal hamartomas, Seizures, Rhabdomyomas, Astrocytomas, Ash leaf
Inheritance of Tuberous Sclerosis?Incomplete penetrance
Mutation in Von Hippel Lindau?VHL gene on Chromosome 3p [VHL has 3 words]: active HIF
What tumors are associated with von Hippel Lindau?Hemangioblastoma (retina, cerebellum, medulla), RCC, Pheochromocytomas

Trinucleotide Repeat diseases

Question Answer
Which diseases exhibit trinucleotide repeats?Huntington's, Myotonic dystrophy, Fragile X, Friedreich Ataxia
Trinucleotide repeat in Huntington'sCAG repeats
With each generation, earlier onset, worsening symtomsAnticipation
X-linked Trinucleotide repeatFragile X!
Which gene is affected in Fragile X?FMR1 gene: mRNA translation of axons and dendrites [Fragile Mental Retardation, fMR=MRna]
2MC cause of Congenital Intellectual DisabilityFragile X syndrome
Mental Retardation
Long face
Large jaw
Everted ears
Fragile X syndrome
Trinucleotide repeat in Fragile X?CGG
AR trinucleotide repeat?Friedrich ataxia
Which trinucleotide is repeated in Friedreich Ataxia?GAA: Frataxin
What does Frataxin do?Mitochondrial protein for Fe detoxification and storage [FrataXin: Fe detoXINg]
Staggering gait
Pes cavus
Hammer Toes
Friedreich ataxia
What is the primary pathology of Friedrich Ataxia?Degeneration of sensory neurons, Cardiomyopathy, DM
Trinucleotide repeat in Myotonic Dystrophy?CTG

Autosomnal Recessive Diseases

Question Answer
Recurrent pulmonary infectionsCF
Meconium ileusCF, Hirschsprung's
Contraction alkalosis and Hypokalemia CF
Fat soluble vitamin deficiencyPancreatic insufficiency in CF
Salty baby?CF
Silvery hairAlbinism
Oliguria in uteroAutosomal recessive polycystic kidney disease (ARPKD)
Cirrhosis, DM, Bronze skin pigmentationHemochromatosis [Bronze Diabetes]
Bronchiectasis, recurrent sinusitisKartagener Syndrome, CF
Infertility + Situs inversusKartagener syndrome
Light skin, intellectual disability, musty body odorPhenylketonuria
Crew cut on x-raySickle cell anemia, Thalassemia (Increased erythropoisis)
Dactylitis + Chest painSickle Cell anemia
Susceptible to SalmonellaSickle cell anemia
Chipmunk faciesThalassemias
Corneal deposits and CirrhosisWilson disease
Parkinsonism, Asterixis, Dementia, Dysarthria, CirrhosisWilson Disease


Sphingolipidoses (except Fabry disease)
Mucopolysaccharidoses (except Hunter syndrome)

Cystic Fibrosis

Question Answer
What gene is defective in Cystic fibrosisCFTR gene on Chromosome 7
What does CFTR encodeTransmembrane Cl- ATP-channel: Secretes Cl- in Pancreatic ducts and Airways, Reabsorbs Cl- in sweat glands
Symptoms of CFRecurrent pulm infections, Bronchiectasis, pancreatic insufficiency
What bacteria is associated with CF?Pseudomonas
Most common mechanism in CF?Misfolded protein Ž protein retained in RER and not transported to cell membrane, causing  Cl− (and H2O) secretion;  intracellular Cl− results in compensatory  Na+ reabsorption via epithelial Na+ channels Ž  H2O reabsorption Ž abnormally thick mucus secreted into lungs and GI tract.
Diagnosis of CF?Chloride sweat test: High [Cl-] > 60 mEq/L in sweat
Newborn CF screeningImmunoreactive Trypsinogen
Reproductive effects of CFInfertility: Bilateral absence of Vas Deferens
Treatment of Cystic FibrosisN-acetylcystine and Antibiotics... can put on fluoroquinolones even no contraindicated in most pediatric pts
What endogenous nutrients need to be replaced in CF?Replace Pancreatic enzymes and Fat soluble vitamins
What is one of the earliest signs in CF?Meconium ileum in newborns
What is the MOA of N-acetylcysteine?Inhaled; cleaves disulfide bonds btwn mucus glycoproteins

Lysosomal Storage Diseases

Question Answer
Deficiency of α-galactosidase A leads toAccumulation of Ceramide Trihexoside
[Fabry disease]
[Cariad Farber has 3 boys]
Pain, Ischemia in GI, HTN, Angiokeratomas (vascular lesions on abdomen/butt)Fabry disease
Deficiency of Glucocerebrosidase (β-glucosidase) leads toAccumulation of Glucocerebroside
MC lysosomal storage disorderGaucher
Hepatosplenomegaly, Painful bony lesions, AnemiaGaucher
Crumpled Tissue macrophagesGaucher cells A: lipid laden macrophages
Treatment of Gaucher'sRecombinant glucocerebrosidase
Femur necrosis - bone crises
Deficiency of Sphingomyelinase leads toAccumulation of Sphingomyelin [Niemann-Pick]
Hepatosplenomegaly + ThrombocytopeniaGaucher and Niemann Pick
[Gaucher has bone lesions, Niemann has Ataxia]
Ataxia, Dysphagia, Dysarthria, Progressive intellectual impairmentNiemann Pick
“Cherry-red” spot on maculaNiemann Pick or Tay Sachs
[NP has hepatosplenomegaly, TS does not]
Foam cellsNiemann Pick (lipid-laden macrophages)
Deficiency of Hexosaminidase A leads toAccumulation of GM2 ganglioside [Tay Sachs]
Tay Sachs PrognosisWorsening of mental physical abilities, Death by age 4
Onion skin lysosomesTay Sachs
Deficiency of Galactocerebrosidase leads toAccumulation of Galactocerebroside
[Krabbe Disease]
[Zoidberg, Galactic]
Primary pathology in KrabbeMyelin sheath: Peripheral neuropathy, seizures, optic atrophy, weakness, delayed development
Prognosis of Krabbe diseaseDeath by age 2
Deficiency in Arylsulfatase A leads toAccumulation of Cerebroside sulfate
[Metachromatic leukodystrophy]
[Arya hates Cersei + Bro]
Muscle wasting, Progressive vision lossMetachromatic leukodystrophy
Deficiency of α-l-iduronidase leads toAccumulation of Heparan sulfate and dermatan sulfate [Hurler]
Coarse facial features, Intellectual disability, Dwarfism, Corneal CloudingHurler [gargoylism]
Deficiency of Iduronate sulfatase leads toAccumulation of Heparan sulfate, dermatan sulfate [Hunter]
Deficiency of Heparan sulfate and Dermatan sulfateHurler and Hunter
Gargoylism + aggressive behaviorHunter

X-linked Recessive

Question Answer
What are the X-linked recessive diseases?Ornithine transcarbamylase def + Ocular albinism
Fabry disease
Wiskott-Aldrich syndrome
G6PD deficiency
Hunter Syndrome + Hemophilia A and B
Bruton agammaglobulinemia + Becker muscular Dystrophy
Lesch-Nyhan syndrome
Duchenne muscular dystrophy

[Oblivious Female will Give Her Boys x-Linked Disorders]
Bruton agammaglobulinemia
Wiskott-Aldrich syndrome
Fabry disease
G6PD deficiency
Ocular albinism
Lesch-Nyhan syndrome
Duchenne (and Becker) muscular dystrophy
Hunter Syndrome
Hemophilia A and B
Ornithine transcarbamylase deficiency.