S4: Genome Determinants of Learning Disability Flashcards
List prevelance of genetic conditions from birth
- 2-3% of all babies are born with a significant problems.
- Of this, genetic conditions are responsible for 50% of causes of deafness, blindness, childhood death, severe learning difficulty and 30% of hospital admissions.
What is a learning disability?
A learning disability is defined as significantly reduced ability to understand new or complex information and to learn new skills. It also includes a reduce ability to cope independently which starts before adulthood with lasting effects on development. The incidence of learning disability is 1-2.5%.
How can learning disability be defined?
The extent of the learning disability can be defined as mild, moderate, severe and profound.
- Mild = IQ of 50-70.
- Moderate = IQ of 35-50.
- Severe = IQ of 20-35.
- Profound = IQ <20.
Describe autism
Autism (autism spectrum disorders) affects around 1% of the UK population, they are developmental conditions present from birth characterised typically by:
- Impaired social interaction.
- Impaired social communication.
- Impaired imagination.
- Repetitive and stereotyped mannerisms.
- Rigid patterns of behaviour.
They can occur in isolation or in combination with learning disabilities. However, learning disability and autism can occur independently e.g. High functioning autistic person.
What is special educational needs (SEN)?
- SEN is a form of support given to children who find it more difficult to learn than their peers of the same age.
- About 20% of children in the UK have SEN.
- Of these about 3% have a statement.
Describe causes of learning disability during pregnancy.
- Prenatal can include maternal infections and teratogens.
- Perinatal can include prematurity and pre/peri/postnatal trauma.
- Postnatal includes serious illness, head injury, poor nutrition and exposure to toxins. These are incidents after birth (anytime in your life!).
Is there an overlap between genetic and environmental causes of disease (multifactorial)?
Yes. Some are purely genetic e.g. DMD, others purely environmental e.g. scurvy. However many do cross over. Rare conditions are generally single gene conditions such as phenylketonuria, the more common diseases are multifactorial!
What is the role of an geneticist?
- Diagnosis.
- Explanation.
- Assessment of genetic risk.
- Predictive testing.
- Prenatal testing.
Why make a diagnosis of LD?
- To help understand the aetiology of the condition.
- To advise family/patient if there are other investigations pertinent to the diagnosis e.g. physical problems.
- To advise patient and family about prognosis and suggest the therapeutic options.
- To discuss genetic aspects of the condition.
- To discuss the risk of recurrence in the family.
- To discuss if prenatal testing/preimplantation diagnosis is available if at risk.
Describe general structure used to make a LD diagnosis
- Determine main concerns you have about the child.
- Observe the child during a consultation.
- Take a thorough history.
- Physical examination.
- Special investigations.
What should a history for LD include?
- Family history.
- Pregnancy history. Consider drug/alcohol exposure, result of antenatal screening tests and scans.
- Developmental milestones.
- Vision, hearing, behaviour, sleep
- Seizures, developmental regression.
What should a physical examination for LD include?
- Dysmorphic/non-dysmorphic (gestalt diagnosis?).
- Malformations -minor/major.
- Neurocutaneous stigmata.
- Neurological signs.
What should special investigations for LD include?
- Biochemical tests.
- Imaging – brain + other organs?
- Genetic tests – array-CGH + targeted testing?
What are cytogenetic abnormalities?
There are a variety of different types of cytogenetic abnormality these involve chromosomes so are defects on the macro level.
- Aneuploidy.
- Translocation.
- Deletions/Duplications.
What are Aneuploidy?
Having an incorrect/abnormal number of chromosomes.
e.g. trisomy 21, turners
3 types of translocation
Reciprocal translocation = when chromosomal segments are exchanged between two non- homologous chromosome.
Non-reciprocal translocations = one-way transfer of a chromosomal segment to another chromosome.
Robertsonian = Occurs between acrocentric chromosomes.
- Translocation can be balanced (all genetic material present) or unbalanced.
What are acrocentric chromosomes?
Most chromosomes are long length of genetic material made up of a short arm (“p arm”) and a long arm (“q arm”), which are joined by a centromere. All the chromosomes have different lengths and the lengths of the q and p arm are also different. Acrocentric chromosomes have a very short p arm and a very long q arm.
- Acrocentric chromosome pairs are 13, 14, 15, 21 and 22.