Neurology Flashcards
What type of inheritance is tuberous sclerosis?
Autosomal Dominant (~70% de novo)
TSC1(hamartin) and TSC2 (tuberin)
Neurological follow up of patient with TS?
MRI 1-3 years
Routine EEG in asymptomatic infants with TSC every 6 weeks until age 12 months and 3 monthly to aged 2.
Routine EEG in other patients
How do you diagnose TS?
2 Major or
1 major and 2 minor
Major:
- Hypomelanotic macules
- Angiofibromas
- Ungal fibroma
- Shagreen patch
- ocular
- Multiple retinal hamartomas
- Multiple cortical tubers or radial migration lines
- Subendymal nodules
- Subependymal giant cell astrocystoma
- Cardiac rhabdomyoma
- Angiomyoliomas
Minor:
- Confetti skin lesions
- Dental enamel pits >3
- Intraoral fibromas >2
- Retinal achromatic patch
- multiple renal cysts
- Non-renal hamartomas
- Sclerotic bone lesions
What can be used to slow growth of subependymal giant cell astrocystomas in TS?
mTOR inhibitors (Everolimus)
What is the TSC gene in tuberous sclerosis responsible for?
Suppresses MTOR function, therefore in TS over activation leads to overgrowth, abnormal differentiation, increased protein translation and growth of tumours.
What anti-epileptic medication is used to treat seizures in TS?
Vigabactrin
What type of inheritance is seen in neurofibromatosis?
Autosomal dominant inheritance
NF1 - 17q11.2
How large do cafe au lait macule need to be to diagnose NF1?
Prepubertal >5mm
Post-pubertal >15mm
Diagnostic criteria for NF1?
Someone who does not have a parent diagnosed with NF1
* If two or more of the following are present:
* Six or more café au lait macules
* >5mm (prepubertal)
* >15mm (pubertal)
* Axillary or inguinal freckling (Crowe sign)
* Two or more neurofibromas of any type or one plexiform neurofibroma
* Optic glioma
* Two or more iris hamartomas (Lisch nodules)
* Distinctive osseous lesion such as sphenoid dysplasia, anterolateral bowing of
the tibia, or pseudoarthrosis of a long bone
* A heterozygous pathogenic NF1 variant with a variant allele fraction of 50%
in apparently normal tissue such as WBCs
* A child of a parent who meets the diagnostic criteria specified above
merits a diagnosis of NF1 if one or more the above criteria are present.
What treatment is available for plexiform neurofibromas in NF1?
MEK Inhibitors (trametinib, selumetinib)
What malignant tumour is associated with NF1?
Malignant peripheral nerve sheath tumour
What are the skeletal abnormalities seen in children with NF1?
Sphenoid dysplasia
Bowing of long bones +/- pseudoarthrosis
What is the gene mutation involved in sturge weber syndrome?
Somatic mutation of GNAQ on chromosome 9q21 - sporadic
What is the ophthalmological complication in Sturge Weber Syndrome?
Glaucoma (choroidal angioma)
What is the cranial complication seen in Sturge Weber Syndrome?
Leptomeningeal angiomata
What is the gene mutation in ataxia telangiectasia?
ATM
What Ig deficiency do children with ataxia telangiectasia have?
IgA
What migraine medication should be avoided in sturge weber syndrome and why?
Triptans - abnormal vasculature can increase risk of stroke
Where is the defect in smooth muscle atrophy?
Anterior horn cell
What is the gene mutation for SMA?
Homozygous deletion of exon 7 of the SMN1 gene = decreased production of survival motor neuron protein –> motor degeneration and muscle atrophy
Autosomal recessive
What is the carrier frequency of SMA?
1:50
6 month old
Hypotonic frog leg posture, poor head control, paucity of anti gravity movements, weak cry and cough, tongue fasciculation’s, bright alert face, areflexic with feeding difficulties and paradoxical respirations?
SMA1
What does a bell-shaped chest on chest xray suggest?
Neuromuscular disorder eg. SMA
What is the treatment for SMA?
AAV9 vector gene therapy Zolgensma (introduces SMN1 gene into patients cells)
Antisense oligonucleotide therapy such as Nusinersen (spinraza) and risdiplam - modulation of low functioning SMN2 gene
