27/10/2019 Flashcards
Hypomelanosis of ito - recall what you know
- chromosomal mosaicism
- skin fibroblasts (as opposed to lymphocytes) show the mosaicism
- symmetrical swirls/streaks of hypopigmentation
- anywhere on body
- multiple organs inolved like eyes, skeletal and brain
- can follow blashko’s lines
- eye f/up needed (cataracts, optic atrophy, retinal detachments)
- no clear genotypic and phenotypic correlation
Incontinentia pigmenti - recall what you know
- X-linked dominant (functional mosaicism)
- IKBKG gene (inhibitor of kapp B kinase gamma)
- lethal in males
- rash evolves with time: vesicular then verrucous, hyperpigmented, atrophic/hypopigmented
- 4 phases: not all occur in the same person
- 80% have other defects: Alopecia, dental (hypodontia, conical teeth and impaction)
- CNS: seizures, ID, hemiplegia, small head
- Ocular: optic nerve atrophy
Give 5 examples of neurocutaneous disorders that have +/- developmental delay, seizures, and various degrees of skin involvement
- Tuberous sclerosis
- Hypomelanosis of ito
- NF 1
- Struge Weber
- incontinentia pigmenti
Give 5 examples of Neural migration disorders
- Agenesis of corpus callosum
- Lissencephaly
- Polymicrogyria
- Porencephaly
- Schizencephaly
What are risk factors for cerebral palsy?
Is there genetics involved?
- Prematurity
- low birth weight
- congenital infections
- growth restriction
- multiple pregnancy
- placental abnormalities
- fetal position
Yes, 14% single gene, 33% copy number variation
APOE (apolipoprotein E) in brain, most studied
Deafness. Tell me about the Connexin 26 gene
- most common mutation for non-syndromic
- 50% of cacusaian population has gap junction protein b2 (GJB2)
- most important component of chochlea
- found on skin
- >100 mutations of GJB2
- two forms of hearing loss: AR is DFNB1 and AD is DFNA3
What are syndromic causes of sensorineural deafness?
What are 4 examples of mitochodrial inheritance pathologies?
- MELAS
- MERRF
- Kearns-Sayne Syndrome
- Leber’s hereditary optic Neuropathy
Recall the visual field defects - based on where the lesion is
Talk about
AD
AR
X-linked dominant
Lissencephaly = recall what you know
What is polymicrogyria associated with and what does it look like on MRI?
What is Porencephlaly? Where are the true ones located?
Recall what you know about Schizencephaly?
What is Neopterin?
- human macrophages make these after being stimulated by interferon gamma
- you can find in urine, serum, and CSF
- it is a breakdown product of guanosine triphosphate
- Clinical: raised in CNS inflammatory, infective and auto-immune diseases eg: NMDA receptor enephalitis, influenza associated encephalitis, Aicardi-Goutieres syndrome
- It’s value: it can accurate detect CNS inflammation when other markers are not raised eg: CSF pleocytosis or CSF oligoclonal bands
- oligonal bands in CSF = clonal production of IgG within CNS so can be present in infective, demyelinating and autoimmune CNS conditions
- CSF neopterin is marker of inflammation, like CRP it increases and reduces with inflammation
- good for monitoring inflammatory and infectious diseases like HIV
When do you use microarray and in what genetic conditions?
A 3 year old girl has been found after ingesting several tablets from her grandmother’s “heart medicine” supply.
She is bradycardic (sinus), hypotensive, has wheezy breathing and is confused.
On arrival to ED, she has a short generalised tonic clonic seizure. What is the appropriate first-line therapy?
- overdose with propranolol
- hypoglycaemia important complication
- treat with glucagon first line, irrespective of whether she is hypoglycemic
A 12 year old Chinese girl becomes unwell shortly after eating her dinner. On further questioning, the family admit to using sodium nitrite as a preservative for the fish used in her meal. The patient is dizzy, and shortly develops blue-ness around her lips and tongue. Oxygen saturations are 72%. On transport to the hospital in the ambulance, she develops further respiratory distress and becomes unconscious. What is the appropriate therapy?.
- overdose of nitrite (common ingredient for preserving food)
- oxidising agent, this class most common cause of methaemoglobinaemia
- antidote: methylene blue
- Other substances that can cause meth: dapsone, local anaesthetics, nitric oxide gas, rasburicase, napthalene, and aniline dyes)
How does glucagon work to combat beta-blocker overdose?
What are the head shapes for:
coronol craniosynostosis
deformational plagiocephaly
lambdoid craniosynostosis
metopic cs
sagital cs
What is Smith-Lemli-Opitz syndrome? Give me 5 facts
- low plasma cholesterol and accmulated precursors
- autosomal recessive
- mut in DHCR7 gene = def of microsomal enzyme DHCR7, needed to complete the final step in cholesterol synthesis
- congenital malformations likely occur because cholesterol is a major component of myelin and contributes to signal transduction in teh dveloping nervous system so you get severe impairment
- spontaneous abortions occur
- Phenotypic variations: microcephaly, cardia and brain malformation, multiple organ system failure
- Treatment: dietary choelsterol like egg yolk, and HMG-CoA reductase inhibition to stop the synthesis of toxic precursors proximal to enzymatic block.
What is Costello syndrome?
- germline mutation in the proto-oncogene HRAS
- coarse face, epicanthal folds, depressed nasal bridge, and deep creases on the palm
- Valvular pulmonary stenosis as well as VSD, ASD, HOCM, hypertrophic subaorti stenosis present in 50%
How do you clinically differentiate the causes of hypotonia from central to muscle?
