Disease and Genetics

Question 1

Your attending tells you to prescirbe N-acetlysteine to the young man on the in-patient floor who has pneumonia. Why would he do that? What is the disease and the genetics in this?

Answer 1

pt has Cystic fibrosis: NAT is given to loose mucous plugs by cleaving S-S bonds (also give dornase alfa)

CFTR gene mutation on chromosome 7 and is Autosomal Recessive

Question 2

Gene defect in the disease with polyps all over the colon

Answer 2

Familial Adenomatous polyposis, Auto Dominant, muation on chrom 5 APC gene

“5 letters in ‘polyp’”

Question 3

Baby with gap btwn 1 and 2 toes, duodenal atresia, Hirpshrung and endocardial cushion defect. See Brushfield spots in eyes and notice prominent epicanthal folds

Dx?

Genetics?

How can we screen for this?

Answer 3

Trisomy 21; Downs

95% from meitotic nondsjnx, 4% from Roberstnian translocation and 1% mosaicism

See Low serum PAPP-A and elevated B-hCG in 1st trimester

Low alpha fetaprotein, high B-hCG, low estriol, increase inhibin A in 2nd trimester

Question 4

What is the defect seen in Hereditary spherocytosis, how do we tx it?

Answer 4

Auto Dom spectrin or ankyrin defect leading to spheroid eythrocytes and hemolytic anemia–> increase in MCHC and tx with splenectomy

Question 5

Neurocutaenous disorder with lots of different organs involved, see LOTS of hamartomas and ash leaf spots: key findings are angiofibromas, cardiac rhabdomyomas and seizures

Disease and inheritance

Answer 5

Tuberous sclerosis

AutoDominant with incomplete penetrance and variable expression which is why people present differently

Question 6

Neurocutaneous disorder: see cafe-au-lait spots, cutaneous neurofibromas.

What is this, what’s the inheritance, what’s the gene defect?

Answer 6

Neurofibromatosis type I or Von Recklinhausen

mutation is on NF1 gene on Chomosome 17; AutoDominant

(Von Recklinhausen and Neurofibromatosis type I both ahve 17 letters)

Question 7

Baby comes in, smells like old socks and missing all development milestones. Dx and inheritance

Answer 7

Phenlyketouria: Auto Recessive

low phenylalanine hydroxylase or low Tetrahydrobiopterin cofactor

tx with low phenylalaine in diet and increase tyrosine in diet as it becomes essential

Question 8

Inheritance pattern and signs of Huntingtons

Answer 8

Auto Dom with anticipation; CAG repeat on chrom 4

see depression, dementia, choreiform mvmt, caudata atrophy and low levels of GABA and ACh in brain

Question 9

Inheritance, signs and symptos of Marfans syndrome

Answer 9

Marfans = AutoDomiant; fibrillin-1 mutation thus CT disorder of skeleton, heart, eyes

(floppy mitral vavle and sublux of lens upward)

Question 10

BAby with severe ID, rocker bottom feet and microphthalmia, microcephaly, with celf lip/palate and polydactyly

Dx

Answer 10

Patua: trisomy 13 from meitotic nondisjunx

see low B-hCG, low PAPP-A adn increased nuchal translucency

Question 11

Alway bilateral, massive enlargement of kidneys d/t mutlpe cyts. What is the mutation?

Answer 11

Auto Domin PKD: mutation in PKD1 on chrom 16 or PKD2 on Chrom 4

Question 12

You are rotating through peds and you are performing a check up. you didn’t have time to look through the pts file and are looking at the baby. It looks like image below, but you keep your cool and do the exam. You note corneal clouding and hepatosplenomegaly

Dx, genetics and inheritance

Answer 12

Hurler syndrome; mucopolysaccharidoses

Autosomal Recessive

Deficient in Alhpa-L-Iduronidase leading to build up of Heparan sulfate and dermatan sulfate

Question 13

Disease the presents with familial tumors of endocrine clangs; pancreas, parathyroid, pituitary, thryoid, adrenal medulla

What is the inheritance pattern and mutated gene?

Answer 13

MEN2A and MEN2B

both are Auto.Dominant and are d/t ret gene mutation

Question 14

What disease have trinucleotide repeats?

Answer 14

Huntingtons: CAG

Fragile X: CGC

Friedrich ataxia: GAA

Myotonic Dystrophy: CTG

Question 15

Common to see cavernous hemangiomas in the skin, mucosa and organs all over. Common to have bilaeral RCC and hemagioblastomas = very vascular tumors with hyperchormatic nuclei; in the retina, brain stem, cerebellum and pheochormocytomas.

What is this

What is inheritance

What is the gene mutation

Answer 15

Von Hippel Lindau diseae

Autosomal Dominant

mutated VHL tumor suppresor gene on chrom 3 = HIF gene is always on and activating angiogenic GFs

Question 16

Pt comes in with giant nuts, he’s a bit slow and has a big jaw and big ol’ ears.

What is the DX? genetics? associated heart findings?

Answer 16

Fragile X syndrome, X-linked defect on FMR1 gene affecting mehtylation

see CGG repeats and mitrl valve prolapse

Question 17

25 yo AA comes to the clinic with severe pain in her left hip when she is sitting or lying down. You notice a necrosis in the femoral head and a crew cut apprearance of the skull (you decide she needed a full body Xray bc you’re stupid) She is on hydroxyurea. What is the pts disease, inheritance and defect

Answer 17

Sickel Cell : put these guys on hyroxyurea to increase HbF

Has autosomal Recessive disease; point mutaiton on HbS of the B chain (glu–> val) on position 6

Question 18

Lady comes in and has severe cramping in her lower left abdomen. You are running tests and notice her BhCG levels are high. You are doing your physical and are listening for heart sounds but there is NOTHING going on onthe left side. Dx? Genetics?

Answer 18

Bitch has Kartageners: in women see ectopic preggers and still situs inversus

this is dyenin arm defect

Autosomal Recessive

Question 19

Pt has issues hearing from both ears and had cataracts as a child. What do you expect to see in the brain?

What is the disease?

What’s the mode of inheritance and genetics involved?

Answer 19

Pt has Neurofibromatosis type 2: see juvinile cataracts and bilateral acoustic schwannomas: see meningima and epnedymoma associated

this is on Chrom 22

(disease of 2s; 2 ears, 2 eyes, 2 brain tumors, chrom 22 and NF2)

Question 20

Inheritance pattern of all the sphingolipidosis except Fabry disease

Answer 20

AutoR

Question 21

Pt comes in that is severely jaundiced and confused. They are having issues talking and swallowing and signs of basal ganglia degeneration. Labs show hemolytic anemia. What is wrong with this pt? Genetics? What are really common symptoms of this disease?

Answer 21

Wilsons

Cu accumulation in liver: cirrhosis and basal ganglia degernation as well as deposits in other spots in brain; low Ceroloplasmin and low hepatic Cu excreation

Bzzz: Kayser Fleischer ring, Asterixis

Autosomal recessive disease; ATP7B gene on chrom 13

Question 22

Pt comes in to his primary care doc and you are rotating through during your 3rd year. The doc orders labs to check pts blood as he has Cirrhosis and Diabete Mellitus. He’s fit and doesn’t drink or have hisotry of Hep C. You notice the pt is very tan and it’s the middle of winter, you inquire about his recent travels. He replies he’s been in fucking wisconsin all winter.

Dx, inheritance and tx?

Answer 22

Hemochromatosis: deposition of iron see: cirrhosis, DM, bronxzed skin.

Can be Autosomal recessive or d/t transfusions

Genetics: H63D on the HFE gene; associated with HLA-A3

Question 23

Auto Dom disease presents with telangiectasia, recurrent nose bleeds, skin discolorations, AV malformations, GI bleeds and Hematuria.

Answer 23

Hereditary Hemorrhagic telangiectasia also known as Osler-Weber-Rendu formaiton

Question 24

Pneumonic for X linked recessive disorders

Answer 24

Oblivious Females Will Give Her Boys X-Linked Disorders

Ocularalbinism, Fabry, Wiskott Aldrich, G6PD deficiency, Hemophelia, Brutons, Lesch Nyan, Duchenne

Question 25

Child comes in with mom and he is playing on the floor. As he stands up, he uses his hands to push up along his legs. His cute little calf muscles looks like he runs all the time. What is dx? genetics? common cause of death?

Answer 25

Duchennes musclar dystrophy: X-linked frameshift: deleted dystrophin from gene DMD

no dystrophin cant anchor muscle fiberts in skeletal and heart muscle

See increase CPK and aldolase but dx with Western Blot and msl biopsy

often die from dialated cardiomyopathy

Question 26

Less severe form of Duchennes seen in adolescence or late adult hood

Dx, Genetics

Answer 26

Becker; see X-linked Point mutaiton

Question 27

Rockerbottom feet, ID, MIcrognathia, low set ears, clenched hands and prominent occiput

Dx, genetics and how can we screen for this

Answer 27

Edwards or Trisomy 18

see LOW PAPP-A and LOW B-hCG 1st

Low alpha-fetoprotein, Low B-hCG, low estriol and low or normal inhibin A in 2nd

Question 28

Elfin facies, ID, hyperCalcemia, with well devo verbal skills and friendliness but lots of anxiety and CV problems

Answer 28

Williams

microdeletion of long arm of chrom 7

Question 29

A child with CF comes to clinic weak and confused after playing soccer and then suddenly collapsing. PE is significant for Hypotension: 60/30 and HR is 130 bpm. Oral mucosa is dry. What caused his excess Na loss with sweating?

Answer 29

mutated CFTR channel: regulates Cl-, Na+ adn water across airways, biliary tree, inetstines, vas defererns, sweat ducts and pancreatic ducts.

When sweat is made in eccrine glands = isotonic then as it goes through eccrine glands; Cl is resorbed via CFTR and Na+ follows.

No CFTR = high Na, high Cl sweat–> hypovolemia and excessive Na loss

Question 31

Newborn presents soon after birth with hypotonia, poor feeding, jaundice, macroglossia, constipation and umbilical hernia. What is the dx and what do you need to do to tx?

Answer 31

Congentital hypothyroidism

dx as soon as you can after birth and give child thryoid hormone replacement to avoid mental retardation

Question 32

Fragile X has 226 CGG repeats on the X chromosome, but what causes the gene inactivation which manifests as mental retardation, facial dysmorphism and macroorchidism?

Answer 32

Gene methylation of cytosine bases which causes gene inactivation

Question 33

Defects is mismatch repair genes cause what sydrome that is characterized by an dincrase in HNPCC?

Answer 33

Lynch

Question 34

Increased chromosomal instability is seen in many disorders and often caused by defects in DNA repair genses. What are four ‘chromosomal instability disorders’?

Answer 34

Xeroderma pigmentosum, Ataxia telangiectasia, Fanconis anemia, Bloom syndrome