Pediatric Neurology Flashcards

1
Q

Major features of Tuberous Sclerosis

A

Clinical Triad: Mental Retardation, Epilepsy, Facial Angiofibromas (adenoma sebaceum)

  • Adenoma sebaceum seen in 80%
  • Periungual fibroma
  • Shagreen patch (connective tissue nevus)
  • 3 or more hypomelanotic patches
  • Multiple retinal nodular hamartomas
  • Cortical tubers
  • SEGAs (subependymal giant cell astrocytomas)
  • Cardiac rhabdomyoma
  • Renal angiomyolipoma
  • Lymphangiomyomatosis (occurs in females; presents w dyspnea, hemoptysis or spontaneous pneumothorax)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Genetics of Tuberous Sclerosis

A

Autosomal dominant neurocutaneous syndrome

Two gene loci have been identified for tuberous sclerosis:

  • 9q34 (encoding hamartin)
  • 16q13.3 (encoding tuberin)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Neurofibromatosis Type I (von Recklinghausen disease)

A
  • NIH criteria: presence of at least 2 of the following—
  • 6 or more café au lait spots
  • axillary or inguinal freckling
  • Optic nerve glioma (pilocytic astrocytoma)
  • more than 2 cutaneous neurofibroma or 1 plexiform neurofibroma
    - > 2 iris hamartomas (Lisch nodules)
  • first degree relative with NF1 by the above criteria
  • distinctive osseous lesion—long bone dysplasias, scoliosis, sphenoid wing dysplasia

Minor features: macrocephaly, short stature, learning disability, hypsarrhythmia, epilepsy, scoliosis, hypertension

Risk of neoplasm:

  • optic glioma (pilocytic astrocytoma)
  • Gliomas are usually astrocytomas of the brainstem, cerebral peduncles, globus pallidus
  • ependymoma, meningioma, medulloblastoma
  • increased risk of leukemia, Wilm tumor, melanoma, pheochromocytoma, medullary thyroid carcinoma, rhabdomyosarcoma
  • risk of malignant transformation of neurofibroma to neurofibrosarcoma is <5% in kids (higher in adults). Presents with rapid growth of lesion & pain
  • can see intracranial aneurysms and Moyamoya
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Genetics of Neurofibromatosis Type I (von Recklinghausen disease)

A
  • AD, Chromosome 17q 11.2
  • mutation on the neurofibromin gene on chromosome 17
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Neurofibromatosis Type II

A

For diagnosis either ONE of the following must be present

1) Bilateral vestibular nerve schwannomas- 90%

2 ) 1st degree relative w NF2 & either of the following in the index case: unilateral vestibular nerve schwannoma; or 2 of the following—glioma, meningioma, neurofibroma, schwannoma

OR TWO of the following must be present

        - multiple meningiomas
        - unilateral vestib nerve schwannoma
        - neurofibroma, glioma, schwannoma, cerebral calcifications or juvenile posterior subcapsular cataracts (schawannomas thus Subcapsular)

(cutaneous findings are less common in NF2 but can see café au lait spots, more commonly see CNS tumors in NF2—schwannoma, meningioma, ependymoma,

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Genetics of Neurofibromatosis Type II

A

AD; chromosome 22

-mutation on merlin gene or schwannomin gene on chromosome 22

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Sturge-Weber Syndrome

A

congenital DO w angiomatosis of face, eye, & meninges

  • (considered a congenital malformation rather than a genetic DO and is not hereditary) 2/2 the persistence of embryonal blood vessels that normally regress during gestation)
  • ipsi facial port wine stain in distribution of V1 present at birth
  • ipsi leptomeningeal angioma (causing contra seizures +/- hemiplegia, homonymous hemianopia)
  • progressive venous infarction of the brain underlying the leptomeningeal angioma leads to atrophy & calcification
  • ocular malformations may cause glaucoma, optic atrophy, or iris heterochromia
  • Glaucoma & ketchup fundus
  • Choriodal angiomas
  • learning difficulties, developmental delay, dental abn, skeletal lesions
  • HA is common; hydrocephalus from increased venous pressure or from extensive AV anastomosis
  • MRI w gad: leptomeningeal enhancement, white matter abn, & unilateral hypertrophy of choroid plexus (vascular malformation may be difficult to see)
  • Szs in 90%; caused by the leptomeningeal angiomas
  • when these angiomas are calcified they appear like “railroad tracks” on CT
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Fragile X syndrome

A
  • Most common inherited form of mental retardation
  • Expansion of CGG repeats in familial mental retardation 1 gene (FMR1) on chromosome X
  • X-linked recessive
  • Males 1/4000, Females 1/8000
  • females less likely to have impairment and physical features
  • males have elongated faces, high forehead, protruberant ears, enlarged testes (BIG EGGS)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Fabry’s Disease

A

X-linked recessive (lysosomal storage DO)

α galactosidase A deficiency

Think of “SPECKS”—because they have “specks” in theirs swimming trunk area

o S STROKE

o P Pain—painful peripheral neuropathy, GI pain also

o E Eye abnormalities- keratopathy (corneal opacity), cataracts, papilledema

o C Cardiac- cardiomyopathy, valvular disease, arrhythmias

o K Kidneys- ARF, CKD, HTN, uremia

o S Skin- angiokeratomas (tiny painless papules) in swimming trunk distribution—buttocks, thigh, groin, lower abdomen

Tx is enzyme replacement

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Genetics of Fabry’s Disease

A

X-linked recessive (lysosomal storage DO)

α galactosidase A deficiency

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Emery-Dreifus Muscular Dystrophy

A

-X-linked

Defect in gene encoding for EMERIN protein

  • contractures at the elbows, ankles, & neck
  • cardiac involvement is prominent & have serious conduction abn often requiring a pacemaker
  • muscle weakness in upper arms 1st then later pelvic girdle & distal legs
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Lennox-Gastaut syndrome

  • Age of onset?
  • Triad of?
A

Appears between ages 1 and 10, sometimes de novo, sometimes after infantile spasms.
• Triad of

(1) multiple seizure types refractory to AEDs,
(2) mental retardation (most), and
(3) slow spike-and-wave (1.5-2.5 HZ) activity on EEG.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Landau-Kleffner syndrome

Age of onset?

Clinical Features?

A

Onset 2-11 years

Language regression - (acquired epileptic aphasia)

  • initial word deafness in setting of normal hearing
  • develop both receptive & expressive aphasia

Multiple sz types—atypical absence, myoclonic, GTCs, tonic, etc

  • EEG: sleep-activated spike discharges. Multifocal cortical spikes, predominantly in a temporal/parietal distribution, frequently bilateral
  • Some pts improve with AEDs (Depakote & Lamotrigine)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

West Syndrome

A

triad of infantile spasms, arrest of psychomotor development and hypsarrhythmia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Vitamin B6 deficiency can cause what in infants?

A

Infantile seizures

can be seen in babies of mothers with Vit B6 deficiency, immediately after the initiation of breast feeding.

  • Tx with pyridoxine is therapeutic and no need to start AEDs for baby
  • see Vit B6 def in those that are alcoholics, malnourished (lack of fruit, grain veggies) and elderly
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Tay-Sachs Disease

  1. Genetics?
  2. Deficiency of what enzyme?
  3. Clinical Features
A

(GM2 gangliosidosis)

  1. Autosomal recessive
  2. Deficiency of Hexosaminidase A
  3. Increase startle response, motor regression, spasticity, blindness w optic atrophy, seizures, Macrocephaly
    May present with sx of motor neuron disease
    Cherry Red spot in the macula

CNS involvement only—NO HEPATOSPLENOMEGALY

17
Q

Sandhoff Disease
1. Genetics?
2. Deficiency of what enzyme?
3. Clinical Features
*What is main distinction from Tay-Sachs?

A
  1. Autosomal recessive
  2. Deficiency in Hexosaminidase A & B
  3. Similar to Tay-Sachs in sx except the GM2 gangliosides accumulate in CNS as well as other organs —HAVE HEPATOSPLENOMEGALY
    Cherry red spot
18
Q

GM1 gangliosidosis (lysosomal storage disease)

  1. Genetics
  2. Deficiency of what enzyme?
  3. Clinical Features
A
  1. Autosomal recessive
  2. Beta galactosidase deficiency – Chromosome 3 (don’t confuse with alpha galactosidase A deficiency which is Fabry’s Disease)
  3. Age onset is 6-18 mos—weakness, incoordination, spasticity, seizures, developmental arrest w subsequent regression
    Cherry red spot
    Hepatosplenomegaly
    Dysmorphic; coarse facial features
19
Q

In what diseases do you see cherry red spot?

A

Tay-sachs
Sandhoff
Sialidosis
GM1 gangliosidosis

20
Q

Prader- Willi Syndrome
1. Clinical Features

  1. Genetics
A

infantile hypotonia, short stature, dysmorphic facies (wide mouth), small feet, hypogonadism, MR, hyperphagia, obesity

-microdeletion on chromosome 15, paternally inherited

21
Q

Angelman Syndrome

  1. Clinical Features
  2. Genetics
A

“happy puppet syndrome” bc of flailing of arms at sides when ambulating

  1. developmental delay, speech impairment, sleep disturbance, unsteady jerky gait/ wide based stance, intractable seizures, hand flapping, frequent/inappropriate laughing, microcephaly, ataxia,
  2. classic example of genetic imprinting caused by a deletion or inactivation of critical genes on the maternally inherited chromosome 15
22
Q

What are the 4 skin findings in TS?

A

Ash Leaf Spots
Adenoma Sebaceum
Shagreen Patch
Ungual Fibromas

23
Q

Patient has MR, seizures and some abnormal skin findings. She died.

What lesions do you see on her brain?

A

Cortical Tuber

(Patient had Tuberous Sclerosis)

24
Q

What condition are these brain findings seen in?

A

Tuberous sclerosis

subependymal nodules

white matter lesions following lines of neuronal migration, cyst like white matter lesions

25
Q

Describe the direction of lens dislocation in the following conditions:
1. Marfan’s syndrome

  1. Homocysteinuria
A
  1. UPward
  2. DOWNward
26
Q

Homocysteinuria

  1. Genetics
  2. Clinical Presentation
A
  1. Autosomal Recessive usually 2/2 defect/deficiency in cystathionine beta-synthase or deficiency in MTHFR (methylenetetrahydrofolate reductase)
  • *Multiple thromboembolic events by age 30**, strokes
  • *Marfanoid** body habitus, epilepsy, mental retardation, osteoporosis, skin pigmentation, livedo reticularis of the lower extremities
  • *Downward lens dislocation**
27
Q

Alexander disease

  1. Clinical Presentation
  2. Findings on MRI
  3. Pathology
A
  1. MEGALENCEPHALY, developmental delay, seizures, spasticity, quadriparesis
  2. diffuse T2 hyperintensities in white matter of FRONTAL lobes 2/2 severe white matter destruction/severe myelin loss; involvement of U fibers
  3. Rosenthal fibers
28
Q

Name the leukodystrophies

  • Include genetic inheritance
A

Leukodystrophies LACK Proper Myelin

Leigh’s Disease mitochondrial or AR
Alexander’s Disease AR
Canavan’s Disease AR
Krabbe’s Disease AR
Pelizaeus Merzbacher Disease X linked
Metachromatic Leukodystrophy AR

29
Q

Which leukodystrophies have BIG HEADS?

A

Alexander’s

Canavans

Megalencephalic leukodystrophy w subcortical cysts