Genetic Disorders

bananas's version from 2015-07-20 20:16

Extra Chromosome

Question Answer
MC TrisomyTrisomy21
Flat facies, epicanthal folds, Single palmar crease, Intellectual disabilityTrisomy21
Duodenal atresiaTrisomy21
Endocardial cushion defect: ASD, VSDTrisomy21
ALL (+AML)Trisomy21 [All fall Down]
MC congenital cause of intellectual disability?Trisomy21
2MC congenital cause of intellectual disability?FragileX
MC overall cause of intellectual disability?Fetal Alcohol syndrome
Quad: Low AFP, Low Estriol, High hCG, High InhibinTrisomy21
Increased nuchal translucency on UltrasoundTrisomy21, Trisomy13, Turner's
95% cause of Down syndromeNondisjunction of homologous chromosomes
Risk factors for Trisomy21Advanced maternal age
5% cause of Down SyndromeRobertsonian 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, Intellectual disability, Hypercalcemia, Verbal skills, Extreme friendliness, CV problemsWilliams syndrome [Will Ferrel in Elf]
Mutation in Williams syndromeMicrodeletion of Long arm of chromosome 7
What specific gene is deleted in Williams 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
7Williams syndrome
Cystic Fibrosis
9Friedreich ataxia
11Wilms tumor
13Patau syndrome
Wilson disease
16ADPKD with PKD2 defect
17 Neurofibromatosis I
18 Edwards syndrome
21Downs syndrome
22DiGeorge syndrome (22q11)
Neurofibromatosis 2
XFragile 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
Berry aneurysmADPKD, Marfan's, Ehlers Danlos, Coarctation
Osteomas+Lipomas+Sebaceous cysts+Colon polyps and CancerGardner
Yellow deposits in eye/tendonFamilal hypercholesterolemia
Telangiectasias+Epistaxis+HematuriaHereditary Hemorrhagic Telangiectasia
aka osler weber rendu
Fatigue+JaundiceHereditary Spherocytosis
Lens subluxationMarfan's [Can also be caused by Homocystinuria, which causes Marfenoid symptoms]
Yellow-Brown pigments in 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 + Seizures + Intellectual disabilityTuberous sclerosis
Tumors in multiple organ systemsVon Hippel LIndau
Which tumors are associated with Tuberous sclerosis?Hamartomas!


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 Telangiectasia
- aka osler-weber-rendu
Skin discolorations
GI bleed
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
MEN1Parathyroid Adenoma
Pituitary adenomas
Pancreatic tumors [PPP]
MEN2aParathyroid Adenoma
Medullary Thyroid Carcinoma
Pheochromocytoma [MPP]
MEN2bMucosal tumors
Medullary Thyroid carcinoma
Pheochromocytoma [MMP]
RET geneMEN2a and MEN2b
Mutation on chromosome 17Neurofibromatosis Type 1
Neurofibromatosis type 1 aka Von RecklinghausenNeurofibromas, Cafe au lait spots, Lesch nodules (pigmented iris Hamartomas)
Neural Tumors (neuro sx)
Congenital pseudoarthrosis
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
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)
Pheochromocyomas are associated with ?MEN2a, MEN2b, VHL
Low serum C1?Hereditary Angioedema

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
Sustained muscle contraction
Gait disturbance
Gonad atrophy
Myotonic Dystrophy

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

Lysosomal Storage Diseases

Question Answer
Deficiency of α-galactosidase leads toAccumulation of Ceramide Trihexoside

[Cariad Farber's 3 alpha galactic boys]
Ischemia in GI
Angiokeratomas (vascular lesions on abdomen/butt)
Fabry disease

[Casper, diaper rash]
Deficiency of Glucocerebrosidase (β-glucosidase) leads toGlucocerebroside
MC lysosomal storage disorderGaucher
Painful bony lesions
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 [+bone lesions]
Niemann Pick [+Ataxia]
Progressive intellectual impairment
Niemann Pick
“Cherry-red” spot on maculaNiemann Pick or Tay Sachs
[NP has hepatosplenomegaly, TS does not]
Foam cellsNiemann Pick
(lipid-laden wrinkled tissue 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
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 loss
Metachromatic leukodystrophy
[Arya goes blind]
Deficiency of α-l-iduronidase leads toAccumulation of Heparan sulfate and dermatan sulfate
Coarse facial features
Intellectual disability
Corneal Clouding
Hurler [gargoylism]
Deficiency of Iduronate sulfatase leads toAccumulation of Heparan sulfate and dermatan sulfate
Deficiency of Heparan sulfate and Dermatan sulfateHurler and Hunter
Gargoylism+aggressive behaviorHunter

X-linked Recessive

Question Answer
Deleted DystrophinDuchenne-Muscular-Dystrophy
X-chromosome p21Duchenne-Muscular-Dystrophy
Duchenne-Muscular-Dystrophy PathologyHypertrophy of distal muscle
Later, Fibrofatty muscle replacement
Walking difficulties
Gower sign
Calf pseudohypertrophy
Genitourinary malformation
Retardation (mental and motor)
Recurrent infections+Eczema+Thrombocytopenic purpuraWiskott-Aldrich syndrome
Gargoylism+aggressive behaviorHunter syndrome
Angiokeratomas (lesions on abdomen/butt)+Burning neuropathicpain+Renal insufficiencyFabry
Delayed development+Hypotonia+Self mutiliationLesch-Nyhan
Enzyme deficiency in Lesch-Nyhan?HGPRT: failure of purine salvage
Enzyme increased in Lesch-Nyhan?Phosphoribosyl-Pyrophosphate-Amidotransferase
↑uric acidLesch-Nyhan
Lethargy+Vomiting+ConfusionOrnithine-transcarbamoylase deficiency
ammonium in 2-year-oldOrnithine-transcarbamoylase deficiency: Urea cycle
Hemolysis with TMP-SMXG6PD-deficiency
Dark urine+High retic count
Jaundice+Anemia after fava beansG6PD-deficiency
Pathway affected in G6PD deficiencyPPP (Glucose→Ribulose-5-phosphate)
- ↓glutathione regeneration
- ↓cholesterol and FA synthesis