Lec 2 Flashcards
What is Huntington’s disease
HD is an inherited neuro-psychiatric disorder causing motor, cognitive and psychiatric dysfunction
The mean age of Onset is 35-44
The features are progressive and the median survival time is 15 to 18 Years after onset
HD additional info
Inherited in an autosomal dominant manner
HD is caused by an expansion in CAG nucleotide repeats in HD gene, located on chromosome 4
HD may demonstrate genetic anticipation I.e. the gene expansion may enlarge, leading to the disease appearing at a younger age or more severely in a later date
This is usually due to paternal transmission
Features of HD
Abnormalities of movement
Early: chorea, jerking and twitching, clumsiness
Later: bradykinesia, rigidity, dystonia
Cognition-forgetfulness, slow thought, impaired mental processing, dementia
Psychiatric disturbances- personality changes, anxiety, agitation, psychosis
Testing for HD
Molecular testing of the HD gene is 100% sensitive and spesific
The HD gene is only gene associated with HD
No other disease are associated with mutations in HD gene
A trinucleotide CAG repeat expansion is the only mutation observed
HD number of CAG repeats that cause disease
Normal: 26 or fewer CAG repeats is
Mutant: observed in individual with or predicted to develop HD: 36 or more CAG repeats (36-39 repeats mean mild disease should be used in context of family history)
Intermediate “mutant allele”: 27-35 repeats, not at risk of developing HD, the expansion is unstable and future generation may develop disease, especially on paternal side
Ethics: genetic testing in children
It is only considered ethical to perform genetic tests on kids when: onset of disease occurs in childhood
When interventions are available to avoid harm from genetic disease (as is the case with surveillance for familial adenomatous polyposis)
Not the case for HD
Discrimination in access for genetic testing
The children should decide for themselves if they want the test
They should also under the implications of results including from job applications and insurers
Yet significant and persistent parental anxiety may override these conditions (sibling has had disease)
Cystic fibrosis CF
Recessive disease
CF is most common life threatening inherited disease in UK
1 in 25 are carriers in UK- 2 thirds of carriers have the mutated delta F508 mutation
Carrier risk increases with family history
Neonatal screening for CF introduced in 2004
What causes CF
SNP change in Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) which is located on chromosome 7
Autosomal recessive disease
Over 900 different mutations worldwide
Most common in UK delta F508- pancreatic deficiency
Testing for CF
CF may be confirmed on the basis of molecular analysis of CFTR gene- doesn’t provide prognostic info
Pulmonary function test
Chest X-ray
Sweat test
Treatment for CF
LUNGS- physiotherapist to help clear mucus from lung
Antibiotic to control infection
Heart and lung transplant in serious cases
GI TRACT- nutritional therapy to maintain weight
Pancreatic enzyme to aid absorption
Bone density monitoring with Ca2+ and vit D
Treatment has increased life expectancy
Pitfalls to avoid
Offering reassurance that they will 100% not going to get disease
Regarding CF as childhood disease
Not referring a couple to genetic counselling if they are a carrier of CF
Failing to request ethnicity before genetic test
Neglecting to give appropriate information when counselling a CF positive diagnosis
Refer all for genetic consultation
FACES
Assessment: gather info
Evaluation: interpreting med records, tests and family history
Communication: share info on condition
Support: help family cope
Follow up: maintaining ongoing communication
