Child Neurology Flashcards
(100 cards)
1
Q
Galactosemia: enzymatic defects
A
- Galactose-1-phoshate uridyltransferase (classic galactosemia)
- Galactosidase
- Uridine diphosphate galacose 4’ epimerase
2
Q
Which galactosemia leads to intellectual delay
A
Galactose-1-phosphate uridyltransferase deficiency (classic galactosemia)
3
Q
PDH deficiency: diagnosis
A
PDH is responsible for the oxidative decarboxylation of pyruvate to CO2 and acetyl CoA.
–> elevations of lactate and pyruvate levels, with a low lactate:pyruvate ratio
4
Q
Encephalocele: most common location
A
Occipital region (more severe)
5
Q
Chromosomal aberrations commonly seen in patients with encephaloceles
A
Trisomy 13 and trisomy 18
6
Q
Cause of phenyketonuria
A
Phenylalanine hydroxylase deficiency (responsible of conversing phenylalanine to tyrosine) –> musty odor
7
Q
Maple syrup urine disease
A
Branched-chain α-ketoacid dehydrogenase complex deficiency, leading to the accumulation of branched amino acids: leucine, isoleucine, and valine
8
Q
Propionic acidemia cause
A
Deficiency in propionyl CoA carboxylase (turns propionyl CoA to methylmalonyl-CoA
–> can cause hematologic manifestations such as pancytopenia and bleeding disorders
9
Q
Cherry red spot + hepatosplenomegaly + foamy cells (vacuolated histiocytes with lipid accumulation)
A
Niemann-Pick type A or B due to sphingomyelinase deficiency
Type A: CNS symptoms + viscera
Type B: only visceral with hepatosplenomegaly and interstitial lung disease
10
Q
Niemann-Pick type C: defect and symptoms
A
Defects in intracellular cholesterol circulation
Ataxia, vertical gaze apraxia, and intellectual impairment.
Path: foamy histiocytes
11
Q
Filipin test
A
If abnormal: demonstrates impaired ability of cultured fibroblasts to esterify cholesterol –> Niemann-Pick type C
12
Q
Vision and hearing loss + MRI showing T2 hyperintense signal changes in the periventricular and subcortical white matter, sparing the U fibers: diagnosis and deficient enzyme
A
Metachromatic leukodystrophy
Arylsulfatase A deficiency –> accumulation of sulfatide
13
Q
Infantile syndromes of peroxisomal dysfunction
A
- Zellweger syndrome
- Neonatal adrenoleukodystrophy
- Infantile Refsum’s disease
14
Q
Zellweger’s syndrome
A
Cerebrohepatorenal syndrome:
- Dysmorphic features with WM changes and abnormalities in neuronal migration
- Liver dysfunction with cirrhosis
- Polycystic kidney disease.
Typical feature: chondrodysplasia punctata
15
Q
HHT genes
A
- HHT1 on chromosome 9, encoding endoglin, which binds TGF beta
- HHT2 gene on chromosome 12, encoding ALK1 (activin receptor-like kinase 1) )
16
Q
Septo-optic dysplasia
A
- Hypoplasia or absence of the septum pellucidum
- Optic nerve and optic chiasm hypoplasia
- Dysgenesis of the corpus callosum and anterior commissure
- Fornix detachment from the corpus callosum
- Arrhinencephaly (agenesis of only the olfactory bulb and tract) and/or hypothalamic hamartomas may be associated features
17
Q
Kearns-Sayre syndrome: triad
A
- Progressive external ophthalmoplegia
- Onset <20 yo
- One of the following:
> Short stature
> Pigmentary retinopathy
> Cerebellar ataxia
> Heart block
> Increased CSF protein (>100 mg/dL)
18
Q
CDG (Congenital disorders of glycosylation) I-a distinctive features
A
- Lipodystrophy with prominent fat pads in the buttocks and suprapubic area
- Inverted nipples
19
Q
Congenital disorders of glycosylation diagnosis
A
Presence of a carbohydrate-deficient transferrin in the serum and CSF
20
Q
Hypomelanosis of Ito
A
Hypopigmented streaks or patches that follow skin lines
21
Q
Parry-Romberg syndrome
A
Progressive loss of facial tissue, cartilage, and bone, leading to hemifacial atrophy, often with ipsilateral loss of eyelashes, eyebrows, and scalp hair
22
Q
Fabry’s disease: symptoms
A
- Neuro: dysesthesias
- Skin: angiokeratomas
- Cardiac: arrhythmias, valvulopathy, cardiomyopathy
- Renal –> HTN and and uremia
- Vascular: endothelial and vascular smooth muscle involvement –> strokes
23
Q
Neurocutaneous melanosis
A
Various types of cutaneous lesions that are abnormally pigmented in association with leptomeningeal melanosis. There is high risk of developing a melanoma.
24
Q
Maffucci’s syndrome
A
Multiple enchondromas (tumors of cartilage) in association with secondary hemangioma formation and skin findings e.g. vitiligo, hyperpigmented patches and nevi, and café-au-lait spots. The enchondromas grow over time, leading to disfigurement and skeletal abnormalities. Twenty to thirty percent of enchondromas may develop sarcomatous changes.
25
Von Hippel–Lindau disease
Multiple retinal, cerebellar, and spinal hemangioblastomas occur. Benign hemangiomas and cysts in various body parts can also occur. Renal cell carcinoma causes significant morbidity and mortality
Autosomal dominant due to a mutation on VHL on chromosome 3 that encodes for a tumor suppressor protein.
26
Incontinentia pigmenti
Skin involvement occurs in stages including vesiculobullous lesions present at birth, verrucous lesions that appear at approximately 6 weeks of age, and then hyperpigmented lesions that follow the Blaschko lines (lines of skin development). Hyperpigmentation decreases over time, with tendency to disappear or become hypopigmented and atretic later in life.
27
Miller–Dieker syndrome
Four-layer variant
Known as lissencephaly type 1
Characterized by lissencephaly associated with microcephaly, typical facies including micrognathia, low-set ears, thin upper lip, short nose with upturned nares, prominent forehead, bitemporal hollowing. Clinical manifestations include global developmental delay, hypotonia and later spasticity, and intractable seizures.
28
Miller Dieker syndrome: mutation
Microdeletions on chromosome 17 in the LIS1 gene, which encodes for a protein involved in regulation of microtubules and dynein function
29
Myoclonic epilepsy, visual deterioration, and cherry-red spots: diagnosis and cause
Sialidosis
Due to deficiency of lysosomal α-N-acetyl neuraminidase (sialidase)
30
Molar tooth sign: diagnosis and symptoms
Joubert's syndrome
Symptoms: developmental delay, ataxia, oculomotor abnormalities, and respiratory difficulties
31
COACH syndrome
- Cerebellar vermis hypoplasia (can have molar tooth sign on MRI)
- Oligophrenia
- Congenital ataxia
- Coloboma
- Hepatic fibrosis
32
Subcortical band heterotopia: mutation
DCX gene on chromosome X in females, which encodes for the protein doublecortin, involved in microtubule organization and stabilization
33
NF1 mutation
NF1 (Neurofibromin) in chromosome 17, a tumor suppressor protein that activates a GTPase that inhibits RAS, a proto-oncogene involved in cell proliferation.
34
NF2 mutation
NF2 (Merlin) in chromosome 22
Encodes for schwannomin or merlin, a cytoskeletal protein involved in cell growth control
35
NF1 vs Legius’s syndrome
Both have café au lait macules and axillary and inguinal freckling but Legius’s syndrome is NOT associated with optic gliomas, neurofibromas, Lisch’s nodules, nor risk of malignancy
36
NF1 diagnosis
Diagnosed by the presence of specific cutaneous findings
- >=6 cafe au lait spots
- Inguinal or axillary freckling
- >=2 cutaneous neurofibromas or one plexiform neurofibroma
- >= Lisch’s nodules, optic pathway glioma, bony lesion (such as sphenoid wing dysplasia, or thinning of long bone cortex with or without pseudarthrosis), and/or NF1 diagnosed in a first-degree relative.
37
Cobblestone malformations: syndromes associated
Autosomal recessive syndromes including Walker–Warburg syndrome (most severe), muscle–eye–brain disease (intermediate severity) and Fukuyama muscular dystrophy (least severe)
38
Homocystinuria: deficient enzyme
Cystathionine-β-synthase deficiency on chromosome 21
39
Periventricular nodular heterotopia
- Neuronal migration disorder
- Due to mutation of in the FLNA gene (FILAMIN A) on chromosome Xq28, which encodes a protein involved in cytoskeleton stabilization and focal adhesions --> disruption in cell migration by impeding attachment of neurons to the radial glia
40
Urea cycle disorders: triad
Hyperammonemia, encephalopathy, and respiratory alkalosis
41
Urea cycle disorders: most common
OTC deficiency
X-linked
42
Porencephalic cysts are lined by
White matter or gliosis
43
Polymicrogyria
Excessive abnormal gyri that are small and separated by shallow sulci
44
Schizencephaly
Deep cleft that extends from the pial surface to the ventricle and is lined with cortex
45
NF1: most common CNS tumor
- Optic nerve glioma (low-grade; may cause symptoms due to mass effect)
- Cerebral, cerebellar, and brainstem astrocytomas
46
NF2: most common CNS tumor
- Schwannomas (bilateral vestibular schwannomas)
- Ependymomas (Spinal ++)
- Meningiomas
47
Rett syndrome
Initially normal development with subsequent regression at 6-18 months of age with hand wringing and other motor stereotypies
X-linked, mutation in the MECP2 gene
48
Mutations in tuberous sclerosis
- Hamartin (TSC1) in chromosome 9
- Tuberin (TSC2) in chromosome 16
49
Major features in TSC
* Hypomelanotic macules (including ashleaf spots)
* Angiofibromas or fibrous cephalic plaque
* Ungual fibromas
* Shagreen patch
* Multiple retinal hamartomas
* Cortical dysplasias (including tubers and cerebral white matter
radial migration lines)
* Subependymal nodules
* Subependymal giant cell astrocytoma
* Cardiac rhabdomyoma
* Lymphangioleiomyomatosis
* Angiomyolipomas
50
Fragile X syndrome: mutation
- Most common inherited form of intellectual disability
- Due to expansion of CGG in FMR1 gene on chromosome X
51
Fragile X syndrome: clinical manifestations
Elongated face, with a high forehead and elongated jaw, protuberant ears, and enlarged testes
Mnemonic:
CGG trinucleotide <--> Child with Giant Gonads)
52
Prader-Willi syndrome
- Profound infantile hypotonia
- Short stature
- Dysmorphic facies: wide mouth
- Small feet
- Developmental delay
- Hypogonadism (with cryptorchidism in males)
- Hyperphagia and obesity
53
Prader Willi vs Angelman: genetic difference
Both are due to microdeletion on chromosome 15q11-q13
- Prader–Willi syndrome: paternally inherited
- Angelman’s syndrome: maternally inherited,
54
Angelman syndrome
Intellectual disability, microcephaly, intractable epilepsy, ataxia, inappropriate laughter with a wide-based stance and flailing of the arms at the sides during ambulation --> happy puppet syndrome
55
Cri-du-chat syndrome
Abnormal, cat-like cry, intellectual disability, presence of epicanthal folds, hypertelorism, micrognathia
Caused by a deletion on chromosome 5p.
56
Williams syndrome
Developmental delay and a happy affect, is associated with congenital heart disease, increased verbal abilities, and “elfin” facies
Caused by deletions on chromosome 7q.
57
Methylmalonic acidemia cause
Deficiency of methylmalonyl-CoA mutase
Leads to accumulation of propionyl-CoA, propionic acid, and methylmalonic acid --> metabolic acidosis, hyperglycinemia and hyperammonemia.
58
Biotinidase deficiency
Biotinidase role: participates in processing of dietary protein- bound biotin
Symptoms: seizures, hypotonia, ataxia, developmental delay, hearing and vision loss, spastic paraparesis, cutaneous abnormalities (alopecia)
Labs: ketoacidosis, hyperammonemia, organic aciduria
59
Dandy-Walker malformation
Cerebellar vermis hypoplasia
- Fourth ventricular cystic dilatation
- Elevation of the torcula and the tentorium cerebelli
- Posterior fossa enlargement and hydrocephalus are common
60
Molar tooth sign: seen in
- Joubert's syndrome
- COACH syndrome (cerebellar vermis hypoplasia, oligophrenia, congenital ataxia, coloboma, hepatic fibrocirrhosis)
- Leber congenital amaurosis
61
Excitatory projection neurons
Pyramidal cells
62
Neurons that function as cortical interneurons and predominate in regions involved in sensory function or integration
Granular (or stellate) neurons
63
The six layers of the neocortex
- Layer I: most superficial, covered by the pia
- Layer II: external granular cell layer - Layer III: external pyramidal cell - - - Layer IV: internal granular cell layer
- Layer V: internal pyramidal cell layer
- Layer VI: multiform layer (deepest layer, overlying the subcortical white matter).
64
Upper motor neurons of the nervous system
Betz cells
Found in layer V of the primary motor cortex
65
Corticocortical efferents
Arise mainly from later III and project to layers II and III
66
Recipients of the majority of thalamic efferents
Layers I, IV, and VI
67
Who gives rise to corticostriate projections
Layer V
68
Who gives rise to corticothalamic projections
Layer VI
69
Gaucher's disease
- Autosomal recessive
- Deficiency of the enzyme glucocerebrosidase leading to lysosomal accumulation of glucocerebrosides
- More common in Ashkenazi Jews.
70
Gaucher's disease: phenotypes
- Type 1: most common, does not involve the CNS early on. Hepatosplenomegaly with anemia and thrombocytopenia, skeletal involvement, and pulmonary infiltrates, increased risk of Parkinson’s disease
- Type 2: onset before the age of 2 years, with psychomotor involvement, spasticity, choreoathetosis, oculomotor abnormalities, and progresses to death by 2 to 4 years of age. These patients may also have hepatosplenomegaly, hydrops fetalis, and cutaneous changes.
- Type 3 begins after the age of 2 years and progresses slowly, with hepatosplenomegaly, psychomotor deterioration, spasticity, ataxia, and oculomotor involvement
71
Gaucher's disease: path
Wrinkled tissue paper
72
GM2 gangliosidosis
- Tay-Sachs: due to hexosaminidase A deficiency. HEXA gene mutation
- Sandhoff’s disease due to hexosaminidase A and B deficiency. HEXB gene mutation
73
Tay-Sachs vs Sandhoff
- Enzymes: TS with Hex A vs Sandhoff with Hex A and B
- Systems affected: TS with CNS only vs Sandhoff with CNS + viscera resulting in hepatosplenomegaly
74
Tay–Sachs disease
- Hexosaminidase A deficiency
- CNS only
- Symptoms: increased startle response, motor regression, spasticity, blindness with optic atrophy, and seizures.
- A cherry- red spot in the macula
- Macrocephaly
- Death by the age of 5 years
75
Psychomotor retardation + cherry- red spot + hexosaminidase A deficiency with normal activity of hexosaminidase B
Tay-Sachs disease
76
Sandhoff’s disease
- Enzyme: Hexosaminidase A + B
- CNS + viscera
- Symptoms: Tay-Sachs + hepatosplenomegaly
77
Canavan disease
- AR
- Due to deficiency of aspartoacylase --> accumulation of N-acetylaspartic acid
- Mutation: ASPA gene on chromosome 17
- Poor fixation and tracking, psychomotor arrest and regression, hypotonia and subsequent spasticity. Megalencephaly is present.
- Involvement of the U fibers on MRI
78
Sturge Weber findings on MRI
Gyral calcifications due to angiomatosis of the leptomeninges and brain giving a tram-track appearance
Also cerebral hemiatrophy
79
Krabbe path
Custers of globoid cells, which are PAS+ multinucleated macrophages with cytoplasmic accumulation of galactocerebroside
80
Krabbe MRI
Symmetric demyelination of the cerebral white matter, with relative sparing of the U fibers
81
Krabbe symptoms
- Infantile form: 4-6 months; irritability, hypersensitivity to stimuli, hypertonicity with opisthotonos, optic atrophy with blindness, psychomotor developmental arrest, and regression; death by 1-2 years
- Juvenile form: 3-10 years; vision loss, spasticity, ataxia, gait disturbance, cognitive impairment.
- Adult form: 3rd-5th decade; spastic paraparesis, weakness, vision loss, evidence of neuropathy
82
GM1 gangliosidosis
- Deficiency in the lysosomal enzyme β-galactosidase
- Symptoms: b/w 6-18 months; incoordination, weakness, spasticity, seizures, psychomotor developmental arrest with regression, cherry-red spot in the macula, dysmorphic, coarse facial features and hepatosplenomegaly
83
Alexander's disease: MRI
- Diffuse WM T2 hyperintensity, predominantly in the frontal lobes and anterior cerebral regions, with involvement of the U fibers.
- Adult-onset: “tadpole sign” on sagittal MRI results from dramatic thinning of the upper cervical spinal cord
84
Alexander's disease: path
Rosenthal fibers
85
Alexander's disease: symptoms
- Infantile form: megalencephaly, developmental delay, seizures, psychomotor developmental delay, spasticity, and quadriparesis.
- Juvenile form: more significant bulbar symptoms.
- Adult form: bulbar signs, hyperreflexia, dysautonomia, ataxia, and sleep apnea
86
Alexander's disease: cause
Mutation in the gene for GFAP
87
Psychomotor delay with nodding movements of the head, pendular nystagmus, and other abnormal eye movements
Pelizaeus–Merzbacher disease
PLP1 mutation on chromosome X
88
Pelizaeus–Merzbacher disease: MRI
Diffuse hypomyelination with T2 hyperintensity sparing the U fibers with “tigroid” appearance
89
Neurovisceral symptoms with attacks of abdominal pain with N/V + limb pain and muscle weakness
Acute intermittent porphyria
Due to PBG (porphobilinogen) deaminase
90
Distribution of muscle weakness in acute intermittent porphyria
Proximal>distal
Arms> legs
Radial nerve ++
91
Diagnosis of acute intermittent porphyria
Elevation of plasma and urinary concentrations of the porphyrin precursors aminolevulinic acid (ALA) and porphobilinogen (PBG)
92
Enlarged orange tonsils
Tangier disease
Due to mutations affecting the adenosine triphosphate cassette transporter protein (ABCA1 gene, 9q31) resulting in a deficiency of HDL
93
Tangier disease: labs
- HDL deficiency
- Decreased cholesterol
- High TG
94
Tangier disease: path
Foamy macrophages in the bone marrow and other tissues
95
Brittle coarse and lightly pigmented hair, hyperelastic skin, thin or absent eyebrows
Menkes disease
Disorder of intracellular copper transport
X linked
96
Menkes disease: cause
Mutation in ATP7A (X-linked), a copper transporter --> defective copper transport across the intestines and across the BBB, with low levels of copper in the plasma, liver, and brain
97
Menkes disease vs Wilson's disease
- Cause: Menkes is due to decreased copper vs Wilson is due to copper accumulation
- Gene: Menkes is ATP7A vs Wilson is ATP7B
- Transmission: Menkes is X-linked vs Wilson is AR
98
Abetalipoproteinemia: cause
Defect in the gene for the microsomal triglyceride transfer protein (MTTP gene) on chromosome 4
99
Symptoms of abetalipoproteinemia
Due to vit E deficiency (due to malabsorption of lipid-soluble vitamins)
Psychomotor retardation with cerebellar ataxia, gait disturbance, decreased proprioception (from demyelination of posterior columns and peripheral nerves), retinitis pigmentosa
100
Abetalipoproteinemia: labs
Acanthocytosis, absence of VLDL, absence of apolipoprotein B, low levels of vit E, severe anemia.
