Cram 4 Flashcards
r i s k o f s e x c h r o mo s o me a ne u p l o i d y w i t h I C S I ?
1 % - ma y b e d u e t o u nd e r l y i ng s e x c h r o mo s o me a ne u p l o i d y i n f a t h e r o r d u e t o I C S I itself.
I f a f e t u s h a s a nu c h a l t r a ns l u c e nc y i nc r e a s e d t o 2 s t a nd a r d d e v i a t i o ns a t 1 1 - 1 4 w e e k s , t h e mo s t l i k e l y k a r y o t y p e f i nd i ng i s
normal karyotype -ri sk of aneupl oi dy i ncreased, but normal outcome sti l l most likely
AR disorders of increased frequency for prenatal carrier screening?-Mediterranean
beta thal : 1/25 al pha thal : /140 (trans) si ckl e cel l : 1/4
AR disordersof increased frequencyforprenatal carrierscreening?-African American
sickle cell: 1/12 alpha thal: 1/30 (trans) Hb C: 1/50 beta thal: 1/65 G6PD-A: 1/10males
AR disordersof increased frequencyforprenatal carrierscreening?-Non-Hispanic Caribbean, W. Indian
sickle cell: 1/12 Hb C: 1/30 alpha thal: 1/30 (trans)
AR disordersof increased frequencyforprenatal carrierscreening?-West African
sickle cell: 1/6 Hb C: 1/25 alpha thal: 1/30 (trans)
AR disordersof increased frequencyforprenatal carrierscreening?-Hispanic (Mexican;Central Amer’n)
beta thal: 1/40
AR disordersof increased frequencyforprenatal carrierscreening?-Asian
alpha-thal:1/20(*cis)beta thal:1/50
AR disordersof increased frequencyforprenatal carrierscreening?-Southeast Asian
al pha-thal : >1/20 (*ci s) beta thal : 1/30
AR disordersof increased frequencyforprenatal carrierscreening?-Asiansubcont (India, Pakistan)
beta thal: 1/50
AR disorders of increased frequency for prenatal carrier screening?-middle eastern
beta thal: 1/50
Sickle cell disease
SS (60-70%); SC, S/beta-thal -anemi a (by 4-5 mo, normocyti c, normochromi c) -
i nf e c t i o n ( mo s t c o mmo n c o mp l ‘ n, p r e v e nt w i t h p e ni c i l l i n p r o p h y l a x i s e a r l y o n) - v a s o - occlusive dis. (50% by 1y, most by 6y) —painful bone/joint crises (ER complaint) —pulmonary crises (50%, hosp’l admis’n) —painful abd’l crises -other: cardiac, CNS,dactylitis,pripaism,oculardis.,renal complic’ns-dx:IEF (usuallyforNBS); HLPC;molecularforprenatal dx-tx:penicllinprophylaxis,vaccination,oral hydration, folate supplements, avoid hypoxia/exhaustion/temp extremes -
Hb Bart disease
on-immunefetal hydrops-usuallydeathinneonatal period -all fouralpha globingenes deleted -really only occurs inasians (b/c cis)
Hb H disease
2 alpha globingenes deleted -mild to moderate microcytic hypochromic hemol yti c anemi a -mi l d j aundi ce -herpatospl enomegal y -thal assemi a-l i ke bone changes -live into adulthood tx - avoid sulfonamides, antimalarias (to prevent h e mo l y s i s ) - mo ni t o r f o r h e mo l y s i s d u r i ng f e v e r - f o l a t e s u p p l ‘ n - t r a ns f u s i o n i f needed during pregnancy
alpha thal trait, silent carrier
“trait” -2 deleted -microcytosis, hypocrhomia, normal % HbA2, Hb F (vs. beta thal trai t) “si l ent carri er” -one del eted -no phenotype
beta-thal major
d x : mi c r o c y t i c , h y p o c h r o mi c a ne mi a ; a b nl p e r i p h e r a l b l o o d s me a r w nu c l e a t e d RBC;reduced HbAwincreased HbA2and Hb F -severeanemiaand hepatosplenomegaly by 6mo-2yo -ironoverload by 10yo -FTT and reduced lifespantx- BMT isHLA-matched sib;if not - regulartransfusionstomaintainHb at 100g/L -chelationto reduce ironoverload and prevent growth retard’n, failure of sexual matur’n
beta-thal intermedia
mi l d e r a nd l a t e r s y mp t o ms - r a r e l y ne e d t r a ns f u s i o n - a t r i s k f o r i r o n o v e r l o a d d u e t o increased intestinal absorptionof excess ironfromineffective hematopoiesis
beta-thal minor(carrier)
asymptomatic ormildlyanemic -MCV<79-MCH<27-Hb<7-minorRBC morphological changes
beta-thal causes
beta-not: complete absence of beta globingenes; increased gamma globinchains beta-plus: variable reductioninbeta globinchains. pheno: mild to severe HbE: thalassemicstructural betachainvariantthatactivatesacrypticRNAsplicesite. Hb E/beta-thal compoiund het - oftensevere, but canbe mild oreven asymptoamtic. HbE/HbE - unaffected.
what makesbeta-thal milder?
HPFH and alpha-thal trait
cystic fibrosis
me d i a n s u r v i v a l : 3 5 y . l o ng e r i f p a nc r e a t i c s u f f i c i e nt d x : - N B S - i nc r e a s e d immunoreactive trypsinogeninblood spot -sweat chloride (positive in>90% of pt) -Cl >50mEq/Lon2occasions-transepithelial nasal potential difference- moleculartesting
f r a g i l e x p r e v a l e nc e , c a r r i e r r a t e s
full mtn:-1/1250males-1/200femalespre-mtn:-1/150women-1/755men
FXTAS phenotype and penetrance?
-short-termmemory loss, executive fxndeficits, cognitive decline -late-onset, progressive cerebellarataxia and intentiontremor, parkinsonism, peripheral neuropathy, lower-limproximal muscle weakness, autonomic dysfxn-age-related penetrance: —50-59 - 17% —60-69 - 38% —70-79 - 47% —>80 - 75%
e mp i r i c r e c u r r e nc e r i s k s f o r d e a f ne s s
i b of deaf chi l d w heari ng parents —-18% —-14% i f GJB2(c26) rul ed out -o f f s p r i ng o f d e a f p e r s o n a nd h e a r i ng p e r s o n - - - 1 0 % ( b / c c o u l d b e A D ) - - - t e s t f o r
GJB2 -offspring of deaf couple with no evident AD syndrome —15%