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?
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
Gene defect in the disease with polyps all over the colon
Familial Adenomatous polyposis, Auto Dominant, muation on chrom 5 APC gene
"5 letters in 'polyp'"
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
How can we screen for this?
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
What is the defect seen in Hereditary spherocytosis, how do we tx it?
Auto Dom spectrin or ankyrin defect leading to spheroid eythrocytes and hemolytic anemia--> increase in MCHC and tx with splenectomy
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
AutoDominant with incomplete penetrance and variable expression which is why people present differently
Neurocutaneous disorder: see cafe-au-lait spots, cutaneous neurofibromas.
What is this, what's the inheritance, what's the gene defect?
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)
Baby comes in, smells like old socks and missing all development milestones. Dx and inheritance
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
Inheritance pattern and signs of Huntingtons
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
Inheritance, signs and symptos of Marfans syndrome
Marfans = AutoDomiant; fibrillin-1 mutation thus CT disorder of skeleton, heart, eyes
(floppy mitral vavle and sublux of lens upward)
BAby with severe ID, rocker bottom feet and microphthalmia, microcephaly, with celf lip/palate and polydactyly
Patua: trisomy 13 from meitotic nondisjunx
see low B-hCG, low PAPP-A adn increased nuchal translucency
Alway bilateral, massive enlargement of kidneys d/t mutlpe cyts. What is the mutation?
Auto Domin PKD: mutation in PKD1 on chrom 16 or PKD2 on Chrom 4
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
Hurler syndrome; mucopolysaccharidoses
Deficient in Alhpa-L-Iduronidase leading to build up of Heparan sulfate and dermatan sulfate
Disease the presents with familial tumors of endocrine clangs; pancreas, parathyroid, pituitary, thryoid, adrenal medulla
What is the inheritance pattern and mutated gene?
MEN2A and MEN2B
both are Auto.Dominant and are d/t ret gene mutation
What disease have trinucleotide repeats?
Fragile X: CGC
Friedrich ataxia: GAA
Myotonic Dystrophy: CTG
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
Von Hippel Lindau diseae
mutated VHL tumor suppresor gene on chrom 3 = HIF gene is always on and activating angiogenic GFs
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?
Fragile X syndrome, X-linked defect on FMR1 gene affecting mehtylation
see CGG repeats and mitrl valve prolapse
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
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
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?
Bitch has Kartageners: in women see ectopic preggers and still situs inversus
this is dyenin arm defect
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?
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)
Inheritance pattern of all the sphingolipidosis except Fabry disease
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?
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
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?
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
Auto Dom disease presents with telangiectasia, recurrent nose bleeds, skin discolorations, AV malformations, GI bleeds and Hematuria.
Hereditary Hemorrhagic telangiectasia also known as Osler-Weber-Rendu formaiton
Pneumonic for X linked recessive disorders
Oblivious Females Will Give Her Boys X-Linked Disorders
Ocularalbinism, Fabry, Wiskott Aldrich, G6PD deficiency, Hemophelia, Brutons, Lesch Nyan, Duchenne
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?
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
Less severe form of Duchennes seen in adolescence or late adult hood
Becker; see X-linked Point mutaiton
Rockerbottom feet, ID, MIcrognathia, low set ears, clenched hands and prominent occiput
Dx, genetics and how can we screen for this
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
Elfin facies, ID, hyperCalcemia, with well devo verbal skills and friendliness but lots of anxiety and CV problems
microdeletion of long arm of chrom 7
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?
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
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?
dx as soon as you can after birth and give child thryoid hormone replacement to avoid mental retardation
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?
Gene methylation of cytosine bases which causes gene inactivation
Defects is mismatch repair genes cause what sydrome that is characterized by an dincrase in HNPCC?
Increased chromosomal instability is seen in many disorders and often caused by defects in DNA repair genses. What are four 'chromosomal instability disorders'?
Xeroderma pigmentosum, Ataxia telangiectasia, Fanconis anemia, Bloom syndrome