Peds Flashcards

Question

congenital aqueductal stenosis

Answer 1

btw 3rd + 4th ventricle (foramen of Monro-lateral+3rd) 1. neurulation disorder -abnormal midbrain development 2. X linked - gyria +/- holoprosencephaly/Chiari II 2. **CMV, mumps** 3. tumors: ependymomas, hamartomas - or secondary compression on aqueduct Sx: macrocephaly, sundowning of eyes, hydrocephalus

Answer 2

1. Zellweger's - PEX mutation (Pachy Poly PEX)-AR -chondrodysplasia, calcific stippling patella, dysmorphic faces, normal head circumference, liver/kidney disease, hearing loss -**pachygyria/polymicrogyria**; white matter involved Dx: -VLCFA in serum, decreased RBC plasmalogens, decrease hepatic peroxisomes -die early 2. neonatal adrenoleukodystrophy - NO pachygyria +heterotopia, cerebellar dysplasia, spares U fibers -cirrhosis, adrenocortical atrophy -VLCFA in serum 3. infantile Refsum's - phytanic acid increased A dominant PHYTING the REF; punching in chest (cardiomyopathy); socks and gloves on-neuropathy AD Autosomal dominant; -motor delay, hearing loss, anosmia, retinitis pigmentosa -cardiomyopathy -large fiber neuropathy (vs KSS-no neuropathy) -short 4th toes -mild, can live to adult -no peroxisomes

Answer 3

Hereditary hemorrhagic telangiectasia+Osler-Weber-Rendu - autosomal dominant - multiple AVMs pseudoxanthoma - thrombosis Ehlers-Danlos - aneurysm, dissection Fabry - ectasia, thrombosis MELAS-infarcts not correlating with vascular territories

Answer 4

peripheral neuropathy, ataxia, hyperkinetic, cog decline

Answer 5

XL ABCD1 gene - peroxisome membrane transport 1. childhood onset cerebral type - 4-8 yrs ADHD behavior problems, aggression -spasticity, incoordination, bulbar dysfxn -no pachygyria; SPARES U fibers -**rim of enhancement posterior white matter** - differentiate (except Alexander’s - contrast enhancement on MRI) -neonatal adrenoleukodystrophy - NO pachygyria -heterotopia, cerebellar dysplasia -cirrhosis, adrenocortical atrophy -adrenal cortex, Leydig cells testis -brain biopsy: perivascular cuffing, +T cells -risk **adrenal crisis** -die early 2. adrenomyeloneuropathy-age 20, sensory neuropathy, sex dysfxn, sphincter control problem, peripheral nerve demyeliantion, no inflammation -can have adrenal insufficiency -female carriers mild Sx 3. pure adrenal insufficiency -Addison crisis elevated VLCFA, elevated ACTH 2/2 adrenal insufficiency Tx: Lorenzo’s oil - 4:1 glyceryl trioleate-glyceryl triercate - if young + ASx BW transplant

Answer 6

**subacute encephalomyelopathy-mitochondrial dysfxn from respiratory chain** -sporadic or familial, maternal inheritance; mutation in mitochondrial/nuclear DNA encoding resp chain subunits -onset within 1 year: hypotonia, loss of head control, poor suck, vomiting, myoclonic jerks -onset >1 year: respiratory prob, apneas, periodic hyperventilation, nystagmus, ophthalmoplegia -lactate elevated in blood+CSF; lactate + pyruvate elevated during exacerbations -**hyperintense BG, substantia nigra, inferior olive, periqueductal gray** Tx: thiamine, if responsive better prognosis

Answer 7

Usually sporadic - mitochondrial DNA deletion or duplication KISS- eyes half closed, not moving, heart stops, ataxic, short HIGH PROTEIN in CSF opthalmoplegia + onset <20 + short stature/pigmentary retinopathy/cerebellar ataxia/heart block/ increased CSF protein -pacemaker b/c heart block -no neuropathy vs Refsum path: *ragged red fibers* in muscles, white matter with spongy myelopathy

Answer 8

**AR** Type I CDG - abnormal glycan synthesis- developmental delay, liver problems, ataxia, retinitis pigmentosa, stroke like episodes, hypogonadism, **carbohydrate deficient transferrin -serum+CSF** **lipodystrophy: fat pads in buttocks, inverted nipples** Dx: serum transferrin isoforms Tx: supportive

Answer 9

1. cerebral hemispheres : single epithelial layer around lateral ventricles-> **ventricular zone**; radially oriented 2. marginal layer forms above ventricular zone; subventricular below -radial glia in ventricular zone sends processes to pia cortex surface and new neurons migrate on **scaffold made by radial glia** to cortical plate -marginal zone: Cajal-Retzius cells-express Reelin, for migration 3. cortex forms inside out - cells migrating earliest form deepest layers first -neuronal progenitor cells: ventricular, subventricular zones -radial glia toward cortical plate-neurons migrate neuronal cell: pyramidal, stellate /cortical granular, **Betz (5th layer motor cortex)** glial cells: astrocytes, oligodendrocytes, ependyma, microglia all 6 layers of cortex by 27 wks gestation -peak migration 12-20 weeks gyri, sulci: 20-36 wks -most cortex neocortex (isocortex) = 6 layers [vs. primitive cortex - fewer layers - archicortex - hippocampus; paleocortex - olfactory, limbic] Layer I - most superficial - pia covers-molecular layer II - external granular cell III - external pyramidal cell - corticocortical efferents (project to II and III layers) IV-internal granular cell V-internal pyramidal cell (Betz) - corticostriate VI - multiform overlies white matter - corticothalamic (cortex to thalamus) Thalamic efferents: thalamus to cortex - I, IV, VI pyramidal cells - III and V: glutamatergic-largest + cortical neurons stellate/granular neurons-II and IV- smaller interneurons

Answer 10

commissural plate-bridge over which axons run ; problems = corpus callosum dysgenesis/agenesis -Aicardi, nonketotic hyperglycinemia -hypertolorism -coronal MRI: racing car sign

Answer 11

1. Neurocutaneous melanosis - leptomeningeal melanoma + giant hair pigmented nevi, congenital melanocytic nevi; risk melanoma -from melanoblasts origin in pia matter) -brain base, brainstem, cerebellum -hydrocephalus 2. Parry Romberg - hemifacial atrophy - loss facial tissue, cartilage, bone, hair (ROMBERG fall TO ONE SIDE - hemifacial) -HA, Horner’s, seizures, hemiparesis -DDx scleroderma, lipodystophy 3. **Maffucci's - enchondromas (cartilage tumor) and hemangiomas** - vitiligo, hypergimentation -CNS tumors, compression by enchondromas 4. Incontinetia pigmenti - vesiculobulous lesions at birth, verrucous lesions 6 weeks, HYPERpigmented lesions following Blaschko lines of skin development -NEMO gene mutation-encodes protein in NF k B pathway (sounds like fish species name) -X linked - +/- neuro delay 5. VHL - retinal, cerebellar, spinal hemangioblastoma - renal cell carcinoma, no skin findings -AD mutation on VHL gene chromosome 3 - tumor suppressor protein 6. Hypomelanosis Ito - hypopigmented streaks following skin lines (Island of Ito - have to look for it in a map) -cataracts, **macrocephaly+eye abnormalities** seizures, -lissencephaly, hemimegalencephaly -detect lines with UV light 7. epidermal nevus syndrome -types include Proteus syndrome (asymmetry; hypertrophy soft tissue + bones), Becker nevus (high plague, breast hypoplasia, rib defects) others: sebaceous, phakomatosis pigmentokeratotica, CHILD syndrome -nevi over face predict CNS involvement; can get **hemimegalencephaly ipsilateral to facial nerve nevus +contralateral hemiparesis** ; other cortical development problems -risk malignancy -basal cells carcinoma, risk astrocytoma -**iris colobomas**

Answer 12

hiccups in utero, **myoclonic jerks** -present within hours of birth, irritable, poor feeding, hiccups **burst suppression EEG** + hypsarrhythmia -agenesis corpus callosum -can’t break down glycine - defects in the genes (GLDC P proteinand AMT) that encode glycine cleavage enzyme system resulting in decreased enzyme activity -enzymes = AR (proteins, membrane transporter AD) -high glycine in CSF; CSF/plasma glycine concentration >0.6

Answer 13

**proliferation: focal cortical dysplasia; megalencephaly** -Focal cortical dysplasia: dysmorphic enlarged cells, **balloon cells**, abnormal lamination +/- tuberous sclerosis **migration: lissencephaly**, periventricular nodular heterotopia, pachygyria, subcortical band heterotopia **organization: polymicrogyria** (NOT migration), schizencephaly, microdysgeneiss, focal cortical dysplasia with normal cell types

Answer 14

microcephaly: can be benign + hereditary macrocephaly: HC > 2 SD above mean -also can be benign+hereditary -2/2 hydrocephalus -or 2/2 megalencephaly - oversized brain-weight >2 SD -Tay sachs, mucopolysaccaridoses, Canavan, Alexander’s -also could be benign familial hemimegalencephaly - enlarged hemisphere - hamartomatous growth - abnormal proliferation -hemiparesis, seizures -Tx. hemispherectomy

Answer 15

**Miller Dieker syndrome -4 layer classic lissencephaly type 1** (smooth MILLER LIGHT (LIST) beer bottle) -microcephaly, micrognathia, low set ears -**LIS1 gene-chromosome 17** - problem with microtubule directed migration X linked lissencephaly - DCX gene-doublecortin in males (DOUBLE COATING) -if abnormal genitalia - ARX gene- + BG abnormal - type I lissencephaly Subcortical band heterotopia - all 6 layers cortex; doublecortin (microtubules) -DCX gene in females (lyonization- random X inactivation) - neurons with normal gene can migrate into cortex -or mosaic mutations

Answer 16

cobblestone lissencephaly- type 2 -no cortical layers -hydrocephalus +muscular dystrophy+eye problems (optic n atrophy, retinal hypoplasia, glaucoma, cataracts) Cobble stone + alpha-Dystroglycanopathies -AR; POMT1, POMT2, LARGE, FKTN 1. muscle-eye-brain disease - eyes less affected+less cortical change vs Walker-Warburg 2. Walker-Warburg -most severe lissencephaly inc. brainstem- brain, eye, muscle dystrophy, elevated CK, cataract, corneal opacity 3. Fukuyama: AR , FKTN gene, fukutin mutation ; more severe muscular dystrophy— frontal white matter changes - weakness, ocular problems , CNS abnormalities, contractures , seizures, intellectual disability biopsy: dystrophic; reduced alpha-dystroglycan

Answer 17

cystathionine synthase deficiency (enzyme so AR) -CBS gene on chr 21 -**elevated blood, urine homocysteine + high methionine** “tall sissy homo high on meth” -ectopia lentus (down and in vs. Marfan up and fans out), Marfanoid habitus -intimal thickening, thromboembolism, stroke -variants: pyridoxine response vs not responsive Tx: B6, B12, low protein diet, low methionine diet, *cystine* supplementation (month of June is 6); betaine Tx alternative pathway to convert homocysteine to methionine

Answer 18

COACH syndrome CHARGE syndrome (coloboma, heart defects, atresia choanae, GU, ear abnormalities) Epidermal nevus syndrome Patau - trisomy 13

Answer 19

Normal morphology neurons, wrong location->never migrated, remained in periventricular area -periventricular nodular/subependymal most common -FLNA gene-X linked - cytoskeleton stabilization - can’t attach neurons to radial glia scaffold -affect females-X linked dominant

Answer 20

Newborn presentation common except arginase deficiency Ornithine transcarbamylase deficiency only X-linked disorder All others AR - carbamoylphosphate synthetase I deficiency **hyperammonemia + encephalopathy + respiratory alkalosis, no AG, normal glucose, no organic acidemia** high glutamine=edema,astrocyte swelling encephalopathy glutamine accumulation ->astrocyte swelling, brain edema **NO organic acidemia, no anion gap** Tx: no nitrogen, no protein, -sodium benzoat during acute episodes; mannitol for edema

Answer 21

pial to ventricle, lined with gray matter cortex closed lip: cortex in contact open lip: cortex separated by CSF vs **porencephaly - lined with white matter**; from CSF cysts acquired in utero, not development

Answer 22

CMV Zellwegers peroxisome

Answer 23

Dx: one of -BL vestibular schwanomas -2 of: unilater vestibular schwannoma +/- 1st degree with NF2 +/- 2 of neurofibroma, schwanomma, meningioma, glioma, posterior subcapsular lenticular opacities -muliple meningiomas + unilateral vestibular schwanomma or glioma/neurofibroma/schwanomma/cataract schwannomatosis ependymoma meningioma Chr 22 - merlin/schwannomin-AD DDx -

Answer 24

underdevelopment limbic system, reduced cerebellar Purkinje cells

Answer 25

frontal lobes small, underdeveloped -superior temporal gyri small -Brushfield’s spots - white spots in iris APP-Chr 21 - amyloid precursor protein (beta-amyloid) - early dementia Leukemia Atalantoaxial instability

Answer 26

XXY - two X chromosome in male -intellectual disability, gynecomastia, wide arm span

Answer 27

RETT: X linked dominant (all oblivious females can pass herRETT boys X linked disorders) -arrest of head growth->**microcephaly** MECP2 - binds methylated DNA DDx-CDKL5 -earlier seizures - X linked CRI-DU-CHAT - chr 5 - cat cry, micrognathia; intellectual disability

Answer 28

MCC intellectual disability -CGG repeats (child with giant gonads) on FMR1 gene (familial mental retardation 1 gene) -RNA binding protein -random X inactivation (lyonization) in females->less severe -long face, protruding ears (Peter II)

Answer 29

Chr 15q11p13 microdeletion Prader Wili - paternally inherited-Maternally derived genes are silenced (imprinted) failure to thrive as infant, hypotonia -wide mouth, small feet, hypogonadism -hyperphagic when older DDx LAURENCE MOON - obesity + intellectual disability Angelman’s - Paternally derived UBE3A gene is silenced (imprinted); Maternal allele is deleted or mutated -microcephaly, epilepsy, ataxia, happy puppet, flailing arms

Answer 30

CMV, Rubella: perventricular calcification 1st tri radiation -> intellectual disability fetal valproate syndrome+ hydantoin (phenytoin) syndrome - intellectual disability fetal alcohol-congenital heart disease

Answer 31

-enzyme recycles B7 + processes dietary biotin AR inheritance, BTD gene **alopecia-TIN ROOF Smooth and shiny** -hearing, vision loss, seizures, ataxia ketoacidosis, hyperammonemia, organic aciduria partial deficiency-10-30% normal enzyme activity, severe <10% Tx: free biotin supplement, can prevent disability if early -once impaired, cannot repair deficits

Answer 32

Oscar the grouch with chocolate bar on head -glucocerebrosidase deficiency-can test in amniotic fluid -accumulation glucocerebrosides -GBA gene mutation Chr I Type I - most common- HSM, anemia, pulm infiltrates; risk Parkinson’s disease otherwise no early CNS effects Type 2 - onset before 2, most severe, die early Type 3 - after 2 yrs, progresses slowly; oculomotor involvement - can Tx with bone marrow transplants wrinkled tissue paper cells Tx: enzyme replacement - imiglucerase, taliglucerase lapha, velaglucerase alpha

Answer 33

tx: alpha-glucosidase

Answer 34

Tay Sachs - hexosaminidase A deficiency - HEXA gene - ONLY CNS affected -increased startle response, motor repression, blindness -cherry red spot, **macrocephaly** -die before age 5 Sandhoff’s disease - hexosaminidase A B deficiency - HEXB gene - CNS + other organs affected ->HSM -rare in Ashkenazi Jews

Answer 35

Megalencephaly AR —symmetric white matter disease + U fibers deficiency aspartoacylase - >accumulate N-acetylaspartic acid (MR spec: peak N acetylaspartic acid) -Ashkenazi Jews -ASPA mutation chr 17 -present 2 months of life; no Tx; death in 20s -Adrenoleukodystrophy: **rim of enhancement posterior white matter** - differentiate (except Alexander’s - contrast enhancement on MRI)

Answer 36

globoid cell leukodystrophy galactocerebrosidase deficiency (eyes on top of head), AR “galacto boobs globoid” cerebro on head, nothing behind eyes = optic atrophy -demyelination + U fibers spared -accumulate galactocerebrosides in macrophages->globoid cells -peripheral neuropathy Infantile - present 4 months (maple syrup urine=at birth); regression -hypersensitivity to stimuli->increase hypertonicity->opisthotonus, low grade fevers, optic atrophy Juvenile - 3-10 yrs Adult - 30s-50s -path: PAS+ globoid macrophages - cytoplasm accumulation galactocerebroside CSF: high protein

Answer 37

GNAQ chr 9, sporadic tram track calcifications -parietal, occipital -from angiomatosis port wine stain - trigeminal distribution -encephalotrigeminal angiomatosis - gyral calcifications from angiomatosis - leptomeninges, brain -CNS involvements more likely is angiomas on face- esp if V1, near eye (no cataracts) -can get enlargement of eye; hemiATROPHY of brain -sporadic inheritance; GNAQ gene mutations Cobb’s syndrome - cutaneomeningospinal angiomatosis - rash over spinal dural angioma Risk: venous stasis, AVMs, venous thrombosis, capillary venous malformation

Answer 38

lysosymal B galactosidase deficiency, AR GLB1 gene accumulate GM1 gangliosides - brain+organs -lipid, neuronal ballooning, atrophy BE ONE Gangly gargoyle gal with red eyes Like Hurler with cherry red spot + gargoyle faces -no mucopolysacchariduria

Answer 39

accumulate glucosaminoglycans - disaccharides-in lysosomes, extracellular matrix -AR except Hunter MPS Type 1-Huler -alpha-L-iduronidase deficiency (A Lazy Idaho Hurler) dermatan+heparin sulfate elevated -gargoyle, corneal clouding, aiway obstructuion megalencephaly; normal at birth; develop Sx over 2 yrs -mild form: Scheie’s syndrome -hepatosplenomegaly -electron microscopy - Zebra bodies Tx: enzyme replacement (doesn’t treat CNS Sx), stem cell transplant Hunter - iduronate-2-sulfatase deficiency (Idaho hunter with rotten SULFUR potatoes + tuber skin lesions) -dermatan+heparin sulfate elevated -like mild Hurler phenotype + ivory colored lesions on back+arms + aggression -carpal tunnel; megalencephaly -X linked **Type III-Sanfilippo - heparan sulfate only-intellectual disability**, no dermatan sulfate accumulation MPS Type IV-Morquio’s syndrome -IQ normal; short, skeletal dysplasia, corneal clouding, cardiac valve, SC compression; GLB1 mutation -high urine glycosaminoglycan-keratan sulfate VI-Maroteaux Lamy-normal IQ VII-Sly’s - hydrops fetalis, intellectual disability IX-Natowicz-deficiency hyaluroinidase, accumulate hyaluronan

Answer 40

GFAP mutation - AD -infant: megalencephaly, spasticity, seizures juvenile - childhood - bulbar Sx adult - bulbar Sx, hyperreflexia, dysautonomia, ataxia, sleep apnea -tadpole sign-saggital cervical spine **Rosenthal fibers** - long corkscrew pink blobs - eosinophilic fibers- myeline loss- enhancing white matter lesions -frontal lobe+anterior+U fibers involved No Tx

Answer 41

hypomyelinating leukodystrophy - X linked recessive -PLP1-proteolipid protein 1 mutation -present first months of life -nodding head, pendular **nystagmus** ataxia, chorea, athetosis, dystonia -optic atrophy -some survive to adults -thinning corpus callosum, SPARES U fibers -**tigroid MRI** (tiger spots demyelination) peripheral myelin spared TIGER PELT - pelizaeus, PLP1 gene

Answer 42

Usually AD; during attack increased ALA + PBG acute intermittent porphyria - PBG deaminase -AD - 6 P’s-PBG deaminase deficiency; painful abdomen, port wine urine, polyneuropathy (motor+axonal, proximal>distal; radial N involved), psych Sx, precipitated by drugs (barbituates), EtOH, starvation -no skin lesions -**high ALA aminolevulinic acid + PBG porphobilinogen**during attack -normal coproporphyrin Tx: hemin, glucose-inhibits ALA synthase variegate prophyria - protoporphyrinogen oxidase deficiency - like AIP but skin findings ; photosensitivity -high coproporphyrin III hepatic coproporphyria -coproporphyrinogen oxidase deficiency -high coproporphyrin porphyria cutanea tarda - cutaneous Sx, no CNS Sx

Answer 43

AR, mutation ATP-binding **cassette transporter protein** - ABCA1 gene, 9q31 (retro healthy tangerine has low cholesterol, high TGs; no hands or feet b/c peripheral neuropathy; TG tonsils; listening to cassettes) -symmetric polyneuropathy-loss pain + temp feet, can mimic syringomyelia -hand weakness, UE+LE weakness -or multi focal mononeurpathy -orange tonsils because TG deposited -**LOW HDL, low total cholesterol, high TG** -bone marrow biopsy: fat laden macrophages, premature atherosclerosis Histo: foamy macrophages Dx: clinical + lipid panel

Answer 44

Kinky hair syndrome, X linked, copper deficiency in liver and brain (7 MENKES MONKEYS trying to steal copper because they’re deficient - monkeys are APES - 7A) ATP7A intracell copper transporter deficiency; no copper for enzyme cofactor (vs Wilson’s copper accumulates-ATP7B-copper high in urine) coarse kinky hair, light colored hair (pili torti) no eyebrows, hyperelastic skin subdurals, hygromas, kinked intra+extra cranial vessels, full cheeks, bone fractures (may suspect abuse) histo: cortex, thalamus, subcortex - loss of neurons, granula, Purkinje cells -low ceruloplasmin + copper

Answer 45

mitochondrial encephalopathy, lactic acidosis + strokes -mtDNA MTTL1 - encodes mtDNA tRNA -onset 2-10 yrs -seizures+migraines+vomiting, anorexia stroke like episodes: altered consciousness, hemiparesis, cortical blindness MRI - strokes not corresponding to vascular territory esp. posterior ; cause seizures lactate: high in blood + CSF biopsy: rapped red fibers Tx: CoQ10, L carnitine, L arginine (acutely for stroke IV)

Answer 46

A BETA 12 MIMIC MTTP ; no vitE bc no fat Bassen Kornweig - AR - MTTP microsomal triglyceride transfer protein -transports TG, cholesterol ester, PL from surfaces - no fat absorption -**demyelination of posterior columns** b/c vit E defect b/c can’t absorb DEAK vitamins -vomiting, loose stools, cerebellar ataxia -lose proprioception hands + feet -Labs: acanthocytosis, **no LDL**, no apo B, low vit E, anemia Tx: restrict TGs, supplements DEAK