Multisystem disease

Question 1

Modes of inheritance in multi-system disorders

Answer 1

chromosomal

single gene disorders

multifactorial

Question 2

what are common problems with multi-system disease

Answer 2

Variable expression within as well as between families
Present to a large variety of different specialists
Family history easily missed

Question 3

Neurofibromatosis Type 1 (NF1)

Answer 3

(Von Recklinghausen disease)

Autosomal dominant

Prevalence 1/2500 - 3500

NIH diagnostic criteria - need 2+ for diagnosis
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

Question 4

what are features of NF1

Answer 4

Macrocephaly
Short stature
Dysmorphic features- “Noonan look”
Learning difficulties
Most have some, often subtle, 10% special schooling, 3% moderate MH
Epilepsy
Scoliosis
Pseudoarthrosis of the tibia
Raised BP
due to renal artery stenosis or phaechromocytoma
Neoplasia
CNS (optic gliomas), endocrine

Question 5

how is NF1 diagnosed

Answer 5

diagnostic criteria

Question 6

Summary for multi-system genetic disorders

Answer 6

Treat the whole patient
Role for co-ordinating specialist
Regular follow up if clinically beneficial
Remember reproductive counselling
Variable expression
Understanding natural history allows early management of complications