MULTI SYSTEM DISORDERS Flashcards
Modes of Inheritance
Chromosomal, Single gene disorders, Multifactorial: Polygenic, haemochromatosis, diabetes
Problems in multisystem disease
Variable expression within families; Present to different specialists; easily missed FHx
Plus side: considerable scope for screening and prevention interventions
NF1 (Neurofibromatosis)
Autosomal dominant Diagnostic criteria: Cafe aulait spots neurofibromas axillary freckling Lisch nodules (specks in iris) Optic glioma thinning of long bone cortex F Hx (any two)
Further features of NF 1
Macrocephaly Short stature Learning difficulties epilepsy scoliosis raised BP (due to renal artery stenosis or phaechromocytoma) Neoplasia
Diagnosis and Management of NF1
annual review BP Spine Tibia for unusual angulation visual acuity ask parent to report unusual symptoms educational assessment
Genetics of NF1
17q (tumour suppressor gene)
Mutations different in different families
50% due to new mutations
Main features of NF2
Acoustic neuroma (bilateral)
CNS and spinal tumours
A few CAL spots
Chromosome 22 gene
Tuberous Sclerosis (TS)
1 in 7000
Triad: Epilepsy- infantile spasms, myoclonic seizures
Learning Difficulty
Skin lesions
Multiorgan hamartomas
Genetics of TS
Autosomal dominant
Variable expressions
Almost full penetrance (symptoms)
TSC1 & TSC2 gene.
Other features of TS
Kidney cysts, eye phakomas, heart phabdomyomas
Cortical tubers, sub-ependymal nodules, astrocytoma
Skin lesions of TS
Angiofibromas, subungual fibromas
myotonic dystrophy
autosomal dominant, CTG repeats increasing severity with generation bilateral late onset cataracts bowel probs, DM, Heart Blk, death post anaesthetic risk
summary
treat patient whole
reproductive counselling
variable expression
