Clinical Genetics in Paediatrics Flashcards
(28 cards)
Uses of a standard karyotype?
Search for:
• Aneuploidy
• Chromosomal translocation
• Deletions
Uses of FISH?
Search for:
• Deletions
• Microdeletions
Uses of PCR amplification and sequencing?
For point mutations
Uses of aCGH?
Aneuploidy, chromosomal translocation, deletion, microdeletion
Uses of Next Generation Sequencing?
Deletions in part of a gene and point mutations
Principles of what aCGH allows?
Allows identification of regions in the genome that have been deleted or duplicated, by comparison with a control DNA sample
Describe results of aCGH
Each dot on a microarray represents a specific genetic region:
• If more patient DNA than control DNA hybridises to the dot - patient duplication
• If less patient DNA than control DNA hybridises to the dot - patient deletion
What can aCGH not be used?
It only detects chromosomal imbalance, not balanced translocations
How many bases need to change to cause a genetic disease?
Only 1 NEEDS to change
How many polymorphisms are there in an average person?
4,000,000
6 points to consider when trying to determine if the genetic change causes disease?
- It is in a gene that matches the phenotype
- It has an effect on gene function
- It is not listed as a polymorphism
- It is in an evolutionarily conserved area of the gene
- It is de-novo in the child
- It is present in other affected family members
Difference between implications of de-novo and inherited?
If it is inherited, it is more likely to be a polymorphism
If it arose de-novo, it is more likely to be causative mutation
Evidence that a mutation is causative?
It is in the right gene (assoc. with the phenotype)
Has the right effect
Found in affected (not unaffected) people; beware of penetrance
Biological evidence
Examples of genetic disorders that cause learning difficulties?
William’s syndrome
Rubinstein–Taybi syndrome (tip of nose hangs down and half-moon eyes)
Basic definition of intellectual disability?
Children/young people who have either a learning difficulty in relation to acquiring new skills OR who learn at a different rate to their peers
Impact this has on conceptual, social and practical domains?
Conceptual - language, reading/writing, maths, reasoning
Social - empathy, social judgement, interpersonal comm skills, making/retaining friendships
Practical - same as for social
Different severities of intellectual disability?
Mild (85% have this)
Moderate (10%)
Severe (3-4%)
Profound (1-2%)
History-taking when confronted with a child with developmental delay?
Parental concerns
PMH, FH, developmental history, SH and about the professionals already inv.
Points to consider in the PMH?
Pregnancy/birth
Feeding/weaning
Medical problems and hospitalisations/illnesses
Points to consider in the FH?
- Hearing
- Vision
- Speech
- Learning
- Epilepsy
- Muscle problems
- Physical disability and/or mental health problems
- Sudden death
Is CONSANGUINITY present?
Physical examination key areas?
Height, weight and OFC (head circumference)
Birthmarks
Dysmorphic features
Systemic examination
Spine
Hearing and vision screen
Areas included in the differential of a child with developmental delay?
Mostly genetic disorders
Metabolic disorders
NM disorders
Environmental issues
Safeguarding issues (neglect, etc)
1st line Ix?
- Creatinine kinase, TFTs, U&Es, LFTs, FBC and film
- Bone group
- Chromosomal microarray
- Check for Fragile X
2nd line Ix?
- Neuroimaging (MRI)
- Lead levels check
- Biotinidase, uric acid, ammonia/lactate, organic and amino acids, oligo and mucopolysaccharides
- EEG/CSF/skeletal survey
