Genetics - Multi-system disease Flashcards
How do genetic disorders affect multiple systems?
- If the gene is expressed in multiple tissues
- in 1 tissue that’s integral to multiple systems
- several genes that have many different functions
In what ways can such disorders be inherited?
1- Chromosomal
numerical e.g. Trisomy 21
structural e.g. translations, deletions, micro deletions
2- Single gene (Autosomal dominant, recessive or X-linked)
3- Multifactorial i.e. Polygenic mixed with environmental factors e.g. DM
What major problems are faced when diagnosing such disorders?
- They can present to multiple specialties
- They tend to have a variable expression
- FH is easily missed
Neurofibromatosis Type 1 (NF1) is an example of an autosomal dominant multi-system disorder. What gene causes it?
Mutation in the tumour suppresor gene 17q
What features are used to diagnose NF1?
2+ of:
- Cafe au lait spots (6+)
- Neurofibromas (2+)
- Axillary Freckling
- Lisch nodules (iris specks)
- Optic glioma
- FH
- Thinning of long bone cortex
How do we manage NF1?
Annual review for:
- BP
- Spine for scoliosis
- Tibia angulation
- Visual acuity/fields
- Educational assessment
In short what is NF1?
A multi-system genetic disorder characterized by:
- Cutaneous finding
- Skeletal Dysplasia
- Benign & malignant NS tumours
NF2 is completely different to NF1, how is it characterised?
Chromosome 22 mutation
Acoustic Neuromas- bilateral
CNS tumours
Spinal Tumours
a few Cafe au lait spots
Another Autosomal dominant condition is Tuberous Sclerosis (TS). What genes cause it?
TSC1 & TSC2
It has almost full penetrance, meaning even carriers have some signs if only on scans
In short what is TS?
A rare genetic disorder causing most benign tumours throughout the body, mostly in the:
- Eyes
- Skin
- brain
- Kidney
- Heart
- Lungs
What is the classic presentation of TS?
Triad of:
- Epilepsy
- Learning difficulties
- Skin lesions
There are also tumours in multiple organs often visible on scans
What skin lesions are present in TS?
Depigmented macules Angiofibromas Fibrous plaque forehead Shagreen patches Ungual fibromas
How do we screen at-risk relatives for TS?
Clinical exam for skin/nail signs Retinal exam for tumour Cranial MRI for tumour Renal US for tumour Echocardiogram for Tumour
What kind of mutation causes Myotonic Dystrophy?
A CTG repeat, it exhibits anticipation (much like Huntington’s) meaning it worsens with each generation
What kind of inheritence is Myotonic Dystrophy?
Autosomal Dominant
