Genetics of Multi-system Disorders Flashcards
What modes of inheritance are there for genetic disorders?
Chromosomal- numerical (trisomy 21) or structural (translations, deletions etc)
Single gene disorders (autosomal dominant/ recessive/ X-linked)
Multifactorial- polygenic, environmental factors (e.g. diabetes)
Why does multi system involvement occur?
Several genes with diverse functions are involved in chromosomal inheritance
Single gene can be widely expressed in different tissues
What are the common problems in multi-system disease?
Variable expression within and between families
Present to larger variety of different specialists
Family history easily missed
What are the genetic features of Neurofibromatosis Type 1 (NF1)?
autosomal dominant inheritance
Gene mutated= 17q (tumour suppressor gene)
50% due to new mutations
Mutations different per family
prevalence 1/2500-3000
What is the diagnostic criteria for NF1?
2 or more of: cafe au lait spots neurofibromas axillary freckling lisch nodules optic glioma thinning of long bone cortex family history or NF1
What other clinical features are there with NF1?
macrocephaly short stature dysmorphic features learning difficulties epilepsy scoliosis raised BP neoplasia
What is the management for NF1?
Annual review of those affected
Review those at risk annually until disease excluded
Review of
- BP
- Spine for scoliosis
- Visual acuity + fields
- Educational assessment
- Ask patent to report any symptoms
What is NF2?
What is its features?
A separate disease to NF1
Gene affected is on chromosome 22
Main features:
Acoustic neuromas
CNS + spinal tumours
Cafe au lait spots
What are the genetic features of Tuberous Sclerosis?
Autosomal dominant 60% due to new mutations Variable expressions Almost full penetrance 2 genes affected = TSC1 and TSC2 on different chromosomes
incidence= 1 in 7000
What is the classic triad of tuberous sclerosis?
epilepsy
learning difficulties
skin lesions
What are the clinical features of tuberous slerosis?
Asymptomatic to severe mental/physical handicap
Learning difficulties in 40% (autistic features common)
Seizures in 65%
Skin lesions: angiofibromas, depigmented macules
Kidneys: cysts
Phakomas in eye
Rhabdomyomas in heart
What clinical examination and screening can occur for tuberous sclerosis?
Skin signs, nails, retinal exam
Cranial MR scan
Renal USS
Echocardiogram
What are the genetic features of myotonic dystrophy?
Autosomal dominant
CTG repeat
Increasing severity in each generation
What are the clinical features of myotonic dystrophy?
Muscle weakness, stiffness, myotonia
Low motivation, bowel problems, DM
Heart block
Bilateral cataract
Which genetic disease has a risk with anaesthetics?
Myotonic dystrophy
- risk of death if not monitored closely
