Genetics- Multisystem Disorder Flashcards
How can the genetics of multisystem disorders exist?
Mutations or Inherited
What chromosomal mutations can exist?
Numerical
Structural
What is an example of a numerical chromosomal mutation?
Trisomy 21
What are examples of structural chromosomal mutations?
Translocations
Deletions
Microdeletions
What are single gene disorders that can cause multisystem disorders?
Autosomal dominant
Autosomal recessive
X-linked
What is an example of an autosomal dominant single gene disorder?
Muscular dystrophy
What is an example of an autosomal recessive single gene disorder?
Cystic fibrosis
What is an example of an X-linked single gene disorder?
Duchenne muscular dystrophy
What is a common problem with multisystem disorders?
Variable expression within as well as between families- sometimes difficult to predict phenotype from genotype
What type of condition is neurofibromatosis Type 1?
Autosomal dominant
What is the NHS diagnostic criteria for Neurofibromatosis Type 1?
2 or more of: • café au lait spots - 6 or more • neurofibromas - 2 or more • axillary freckling • Lisch nodules (specks in iris) • optic glioma • thinning of long bone cortex • family history
How is Neurofibromatosis Type 1 diagnosed?
Clinical diagnosis using diagnostic criteria
What is done for someone at risk of neurofibromatosis type 1 until diagnosis can be excluded?
Annual review of affected individuals and at risk children until diagnosis can be excluded (5 years)
What is checked for in someone with possible neurofibromatosis type 1?
- BP
- spine for scoliosis
- tibia for unusual angulation
- visual acuity and visual fields
- educational assessment
What are some other possible features of Neurofibromatosis type 1?
- Learning difficulties
- Scoliosis
- Pseudoarthrosis of the tibia
- Raised BP
What gene is associated with NF1?
17q- tumour suppressor gene
What are the main features of NF2?
- acoustic neuromas- usually bilateral
- CNS and spinal tumours
- a few CAL spots
Where is the gene for NF2 located?
Chromosome 22
What is the classic triad of tuberous sclerosis?
- Epilepsy
- Learning difficulty
- Skin lesions
What can present in different organs with tuberous sclerosis?
Hamartomas
What type of condition is tuberous sclerosis?
Autosomal dominant
What are the 2 genes associated with tuberous sclerosis?
TSC1
TSC2
on different chromosomes
How does tuberous sclerosis differ between family members?
Variable expression between family members- severity varies
What are the clinical features of tuberous sclerosis?
Learning difficulties Seizures Skin lesions Kidney cysts and angiomyolipomata Phakomas in the eye Rhabdomyomas in the heart
What features of learning difficulties are present with TS?
Autistic features are common
What type of seizures are common with TS?
- infantile spasms
* myoclonic seizures
What type of skin lesions are common with TS?
- depigmented macules
- angiofibromas
- fibrous plaque forehead
- shagreen patches
- ungual fibromas
Why is screening at risk relatives important for angiomyolipomata important?
They may develop renal tumours
What examinations would you do for tuberculous sclerosis?
- Nails
- retinal examination
- Cranial MR scan- brain features
- Renal ultrasound- renal cysts or tumours
- Echocardiogram
What is myotonic dystrophy?
Distal muscles and diaphragm become weak
What type of condition is myotonic dystrophy?
Autosomal dominant
What is myotonic dystrophy caused by?
CTG repeat which exhibits anticipation with increasing severity in each generation
How does myotonic dystrophy present?
- Bilateral late-onset cataract
- Typical: muscle weakness, stiffness & myotonia
- Low motivation
- Bowel problems
- Sometimes diabetes mellitus
What is a common cause of death in myotonic dystrophy?
Heart block
Why does the patient need to be monitored post anaesthesia?
Risk of death
What can present in congenital myotonic dystrophy?
Severe muscle disorder and learning difficulties
Death
