Child Neuro / Genetic disorders Flashcards
(123 cards)
0
Q
anencephaly is due to what brain defect and when does it occur?
A
24 days gestation, failure of anterior neural tube closure
1
Q
What visual function is present at birth?
A
black/white vision
2
Q
myeloschisis is what, when does it occur?
A
failure of posterior neural tube closure. Neural structures protrude and expose spinal cord
3
Q
encephalocele is due to what problem, what is the defect?
A
failure of anterior neural tube closure; intracranial contents herniate through midline skull defect
4
Q
what lab test might be elevated in encephalocele?
A
elevated alpha-fetoprotein
5
Q
What syndromes may have encephalocele?
A
Meckel-Gruber syndrome
6
Q
What is Meckel’s syndromle?
A
Microcephaly Encephalocele Cleft lip Kidneys polycystic Eyes small: microphthalmia Lots of fingers: polydactyly Sex ambiguous
7
Q
Difference bewteen myeloschisis and myelomeningocele
A
membrane covering in myelomeningocele
8
Q
Def of arnold chiari type 1
A
cerebellar tonsillar displacement: 5mm through foramen magnum
9
Q
Define type 2 Chiari malformation?
A
cerebellar tonsil displaced
medulla inferiorly displaced (may be kinked)
lumbosacral myelomeningocele
beaked tectum
10
Q
Chiari III malformation?
A
Type II + occipital encephalocele
11
Q
Type IV chiari?
A
Cerebellar hypoplasia
12
Q
secondary neurulation refers to what?
A
formation of caudal neural tube w/ lower sacral and coccygeal segments - causes dyraphic states; abnl filum and conus
13
Q
Caudal Regression Syndrome?
Who is at risk?
A
malformations of caudal region: hindgut, GU, caudal spine, spinal cord and lower limbs
Infants of diabetic mothers
14
Q
dastematomyelia
A
bifid spinal cord (septum divides sc longitudinally)
15
Q
Myelocystocele
Associations?
A
dilation of central canal of caudal neural tube
GI or GU anomalies (bladder/cloacal extrophy, imperforate anus, omphalocele)
16
Q
Schizencephaly is a disorder of what developmental issue?
A
segmentation
17
Q
schizencephaly gene mutation?
A
EMX2 on Ch10q26.1
18
Q
Holoprosencephaly defects? (3 types)
Type of disorder
A
prosencelphalic cleavage disorder
Causes olfactory bulb/tract absence, midline facial defects, cyclopia, organ malformations.
1. Alobar: most severe: single ventricle, no separation of hemispheres, absent CC, fused thal/BG
2. Semilobar: posterior hemisphere separation, splenium cc present
3. Lobar: absent septum pellucidum, incomplete formation of interhemispheric fissure and cerebral falx
19
Q
possible gene for holoprosencephaly
A
sonic hedgehog on 7q36
20
Q
What is aicardi syndrome? (triad and genetics)
A
X-linked dominant
- agenesis of corpus callosum
- infantile spasms
- chorioretinal lacunae
21
Q
Septo-optic dysplasia characterized by what?
Genetics?
A
optic nerve hypoplasia, absence of septum pellucidum, hypopit (may have hypothal)
SOD: 3 letters, Chrom 3 (HESX on 3p21)
22
Q
Miller-Dieker syndrome characteristics and genetics
A
lissencephaly, microcephaly, sz, craniofacial, cardiac
Genetics: 17p13.3 deletion (includes LIS1 gene and 14-3-3)
23
Q
DCX gene on chr xq22 in isolated lissencephaly presents in m/f?
Encodes for what?
A
Males: lissencephaly,
females (heterozygous): subcortical band heterotopia
Double cortin (double standards in M/F)
24
Lissencephaly more severe anteriorly vs posteriorly (gene)
anteriorly: DCX mutation
posteriorly: LIS1 mutation
25
4 diseases on chromosome 17:
1. NF1
2. Alexander's Disease
3. Canavan's Disease
4. Miller Dieker syndrome
26
Gene for lissencephaly with absence of corpus callosum and what is the presentation?
ARX on Xp22.13:
lissencephaly, absence of CC, sz, hypothalamic issues (hypothermia), ambiguous genitalia
(Are you XX or XY: ARX)
27
Gene with lissencephaly and cerebellar hypoplasia
RELN at 7q22 (Reelin)
| Reelin from unsteadiness
28
3 diseases with cobblestone lissencephaly
* syndromic congenital dystrophies : no cortical recognizable layers
1. Fukuyama
2. Muscle-eye-brain disease
3. Walker Warburg syndrome
29
Genetics of Walker warburg?
mutation in POMT1 on chr 9q34
30
GEnetic cause of periventricular nodular heterotopia, genetics?
FIL-1 xq28 encodes filamin-1, usually female (males lethal)
| *mutations in FIL-1 cause heterotopic neurons to FILL the ventricle
31
oculomotor apraxia, hyperpnea alternating with central apnea in neonates, cerebellar vermis agenesis
Dx and characteristic finding?
Joubert syndrome. Midbrain/hindbrain junction looks like molar tooth
32
pontocerebellar hypoplasia, inverted nipples, abnormal fat pads?
Dx
Congenital disorder of glycosylation Ia
33
Genetics of familial hemiplegic migraine
CACNA1A voltage-dep P/Q type calcium channel 1A gene on Chr 19p13
34
Three diseases with CACNA1A mutation on chr 19p13
Familial Hemiplegic migraine 1
Episodic ataxia-2
Spinocerebellar ataxia 6
35
Mutation in Familial hemiplegic migraine 2
ATP1A2 gene on chr 1
36
TORCH infx?
Toxo, Rubella, CMV, HSV
37
Cayler syndrome?
aka cardiofacial: hypoplasia of depressor anguli oris: asymm crying faces. Think Cardiac too
38
Duane syndrome?
absence or hypoplasia of abducens nucleus and nerve w/ aberrant innervation of LR by CN3
39
What is mobius syndrome?
Congenital facial diplegia w/ abducens palsy and +/- NM abnormalities
40
Vein of galen malformation is actually what dilated?
median prosencephalic vein of Markowsky dilation
41
What is Masa syndrome? Genetics?
X-linked recessive, L1CAM gene
MR, Aphasia, Shuffling gait, Adducted thumbs
(aqueductal stensois, agenesis of cc
42
CRASH Syndromes?
CC hypoplasia, mR, Adducted thumbs, Spastic paraparesis, Hydrocephalus
-all X-linked recessive L1CAM w/ hydroceph, Spast paraparesis 1, CC agenesis, MASA
(better for MASA than NASA to CRASH a CAMaro)
43
Dandy Walker syndrome? (triad)
| associated sx?
Agenesis of cerebellar vermis
Cystic dilation of 4th V
Enlarged posterior fossa w/ elevated tentorium
May be assoc w/ occipital encephalocele, DD, cortical malf, sz, polycystic kidneys, cardiac
44
PHACES?
```
Posterior fossa malformation
Hemangiomas of FACE
Arterial anomalies
Coarct Ao
Eye abnl
Sternal clefting / supraumbilical raphe
```
45
Draw sutures and types of craniosynostosis
1. Coronal: gives brachycephaly
2. Metopic gives trigonocephaly
3. sagittal gives scaphocephaly/dolichocephaly
4. lambdoid gives posterior displaced ear (trapezoid)
5. deformational gives anterior placed ear (parallelogram)
46
Apert syndrome?
| Genetics / inheritance
coronal craniosynostosis, syndactyly, proptosis, hypertelorism
(Can't get fingers apart)
FGFR2 on 10q26, AD
47
Carpenter disease and inheritance
multiple suture abnl causing clover leaf deformity, polydactyly (lets carpenter hold tools), MR
AR
48
Crouzon's
| -dz and geneticas
craniofacial dysostosis: beaklike nose, maxillary hypoplasia, but NO syndactyly unlike Aperts
Same genetics: AD, FGFR2 on 10q26
49
broad thumbs, polydactyly, craniosynostosis?
Pfeiffer syndrome
50
clover leaf skull deformity, polydactyly, ID
Carpenter disease
51
soft tissue swelling that crosses suture lines in newborn
caput succedaneum
| -succeeds in crossing suture lines
52
Repeat for FRagile X is what?
CGG (C giant gonads)
53
possible genetic changes in Angelmans? (4)
1. deleted maternal 15q11-13
2. duplicated paternal
3. ubiquitin protein ligase mutation from mom
4. imprinting center
54
Genetic issue in prader willi (2 possible)
1. deleted paternal 15q11.13 or 2. duplicated / /maternal disomy
55
```
what dx:
holoprosencephaly
DD
apnea
omphalocele
polycystic kidneys
CV abnormality
```
T13: Patau
56
```
dx?
ID
flexion deformity
overlapping fingers
rocker bottom feet
omphalocele
polycystic kidneys
CV abnormality
```
T18, Edwards
57
Mutation in William's system what does it affect?
chr 7q11.23 - elastin gene
58
stellate iris pattern in what?
Williams
59
Chromosome / genetics of CHARGE
| What is charge?
Coloboma eye
Heart
Choanal atresia
Retarded growth/mental
CHD-7 (has CHD) and its CHargeD. AD, Chr 8q12.1
60
Digeorge?
Cardiac Abnormal T cell down Clefting Hypocalcemia- chr 22q11 del
61
3 possible RETT mutations?
MECP2 deletion, CDKL5, STK9
62
4 phases of Rett?
1. early onset (3-6 mos acquired microcephaly, DD, ASD like, hand wringing
2. regression 1-4y w/ loss of purposeful hands and speech, autonomic issues
3. stabilization
4. late motor loss of walking
63
Greek helmet facies, high hairline, frontal bossing, hypertelorism, clefts, ID, microcephaly
Dx and genetics?
Wolff-Hirschhorn, 4p16 deletion
64
aberrant mouth, eyelid connection
Marcus Gunn syndrome
65
normal head growth in first 3 mos, next 3 mos, 7-12 mos
Start at 35cm
0-3: 2cm/mo
4-6 mos: 1cm/mo
7-12 mos: 0.5cm/mo
66
PArt of the night for night terrors? type of sleep?
first two hours of falling asleep, slow wave sleep
67
who gets confusional arousals, what part of night, type of sleep?
babies/toddlers, first 3 of night in SWS
68
Timing of breath holding spells
onset 2 mo-2y
| resolves by 6-8yr
69
dx of tourettes
vocal and motor tics for at least 1y
70
4 meds for tics?
1. tenex
2. clonidine
3. pimozine
4. risperdal
71
chromosome for Wilsons and inheritance
AR, Chr 13
72
Inheritance and treatment for paroxysmal kinesigenic choreoathetosis
AD, Carbamazepine/BZD
73
Chr / genetics of huntingtons
CAG repeat on Chr 4 (catch animal game)
74
iron accum in brain
what dz
what eye findings
inheritance
PANK2 (Hallervorden-Spatz)
Chr 20, AR
mutation in pantothenate kinase gene
Eyes: retinal degen, pigmentary retinopathy, optic atrophy
75
FEature of dopamine responsive dystonia
tends to worsen with fatigue and exercise
76
common dystonia in Ashkenazi population
| genetics / inheritance
DYT1 (type 1 dystonia) AD chr 9, variable penetrance
77
where does spinal cord end
L1-2 (same as adult)
78
when does neural tube close?
21-29 days
79
avoid what AED / sz tx in suspected inborn error of metab?
VPA, ketogenic diet
80
ETC complex entirely nuclear dna enconded
Complex II
81
MERRF amino acid issue vs MELAS
MERRF: tRNA lysine point mutation
MELAS: tRNA leucine
82
chronic progressive external ophthalmoplegia
Kearns-Sayre Syndrome
83
What are POLG1 mutations
- what chr
- what for/mechanism
- what disorders
Chr 15
used in replication of mitocho DNA
Mitoch dna depletion syndromes: Alpers, MNGIE
84
painless progessive central vision loss, Wolff Parkinson White, ID, MS like sx
Dx?
Leber Hereditary Optic Neuropathy
85
```
coarse facial features, HSM, and neurological deterioration
suspect what class of disorders
```
Lysosomal Storage Disease
86
developmental delay, epilepsy, agenesis corpus callosum, hypotonia, Wilm's tumor
MACROCEPHALY
Soto: cerebral gigantism
87
PTEN mutation (2 names)
Bannayan-Riley-Ruvalcaba OR Riley-Smith
88
large subdural fluid spaces and hemorrhages mistaken for NAT seen in what disorder?
glutaric aciduria Type 1
89
holoprosencephaly assoc w/ what gene mutation
sonic hedghog
90
schizencephaly with what common gene mutation
| assoc w/ what?
sonic hedghog
| other organ malformations
91
kidney fibrosis, pons and cerebellar hypoplasia, abnormal breathing, jerky eye movements
- Dx
- MRI sign
Joubert
| Molar tooth sign (long cerebellar peduncles)
92
Trisomies that can cause a cerebellar hypoplasia and major brain malformations
T9, 13, 18
93
age for tandem gait dev?
6y
94
age to follow three step commands
4y
95
when can kid unbutton?
3y
96
heart issue that may be assoc w/ congenital hearing loss
long qt (Jervell and Lange-Neilson)
97
TSC gene mutation (2)
| % spontaneous
TS1 chr 9q34 hamartin
TSC2 chr 16q13.3 tuberin
50% spontaneous
98
Stages of incontinentia pigmenti
vesicular stage at birth
veruccous stage
hyperpigmentation between 3-6 mos
hypopigmentation / atrophy in adult women
99
genetics / inheritance of incontinentia pigmenti
X linked dominant Xq28 or XXY
| NEMO gene
100
Inheritance of sturge weber?
usually sporadic
101
leptomeningeal vascular angiomatosis with tram track calcification
Other eye issues?
Sturge Weber
| Glaucoma
102
Increased AFP and CAE and poor immunity with lack of T helper cells, absent IgA and/or IgE what dz and what main sx? Inheritance?
Ataxia telangiectasia
AR ch11q22-23 (ATM gene: Ataxia Telang, Mucus)
Progressive movement d/o and ataxia, oculocutaneous telangiectasias, ID, endocrine issues, recurrent sinopulm infx
103
Chr involved in Van Hippel Lindau. What CNS / tumor issues?
Chr 3, 11 (Autosomal dominant)
hemangioblastomas of brain and retina
also pheos, kidney/pancreas tumors
104
swirly pigmentation
| -give rise to what?
hypomelanosis of Ito
| Whorls give rize to Blaschko's lines
105
what causes hypomelanosis of Ito? genetics
somatic mosaicism xp11
106
CNS issues with hypomelanosis of Ito
epilepsy/ID , grey matter heterotopia, macrocephaly, hemimegalancephaly, asd
infantile spasms
107
Linear sebaceous nevus syndrome may be assoc w/ what CNS abnormality
hemimegaliencephaly
108
Klippel Trenaunay Weber assoc w/ what triad
| what genetics
port wine stain, varicose veins, bone/soft tissue hypertrophy of extremity
sporadic chr 8q mutation
109
Syndromes / neurological conditions with defective DNA repair (3)
1. Ataxia Telangiectasia
2. Cockayne
3. xeroderma pigmentosa
110
MRI finding in Ataxia Telangiectasia
cerebellar atrophy, may also have degen of posteiror columns and loss of DRG cells/anterior horn cells
111
Characteristics of Ataxia-Telangiectasia: ATAXIA
```
Ataxia
Tremor/movement d/o
Apraxia-oculomotor
X-ray sensitivity
Infx/Igs low, Incr cancer *lymphoma/leukemia
ATM gene
```
112
What dz:
| Progeria, cataracts, photosensitivity, short stature, decreased fat and CNS issues
Cockayne
--ID, ataxia, BG calcifications, patchy demyelination, peripheral neuropathy, pigmentary retinopathy, deafness, contractures
113
--ID, ataxia, BG calcifications, patchy demyelination, peripheral neuropathy, pigmentary retinopathy, deafness, contractures
DNA repair defect
Cockayne
114
Side of nevus compared to other (2) abnormalities in linear sebaceous nevus syndrome?
Ipsilateral hemihypertrophy and/or hemimegalencephaly
115
common musculoskeletal issue in Hypomelanosis of Ito
hemihypertrophy
116
What is the mechanism of defect in NF?
lack of neurofibromin leads to active GTP-RAS which a proto-oncogene that remains active and leads to increased cell growth / tumor formation
117
Big heads and little heads associated with chromosome 17?
Macrocephaly: NF1, Alexander's, Canavan's
Microcephaly: Lissencephaly (LIS1), Miller-Diecker
118
Chromosome and defective protein in NF2
Chr 22, Merlin mutation
119
Disease to think about w/ recurrent epistaxis
| Presenting when?
hereditary hemorraghic telangiectasia (HHT) / Osler-Weber-Rendu syndrome (nosebleeds around age 12y)
120
typical location of leptomeningeal angioma and in what disease
Sturge Weber
| usually ipsilateral occipital region
121
Genetic mutation in Von Hippel Lindau?
```
Chromosome 3
(VHS tapes on channel 3)
```
122
acquired microcephaly, dementia, sensorineural hearing loss, ataxia, peripheral neuropathy
Dx and other risk?
Xeroderma pigmentosa
| Defective DNA repair: incr risk skin cancer / photosens
