Genetic - multisystem disease

Question 1

What are examples of chromosomal abnormalities leading to multisystem disorders?

Answer 1

Numerical ie trisomy 21

Structural - translocations, deletions, etc

Question 2

What types of single gene disorders can lead to multisystem disease?

Answer 2

Autosomal dominant
Autosomal recessive
X-linked

Question 3

What are challenges in hereditary multi-system disease?

Answer 3

Variable expression within and between families
Presents to large number of different specialists
Family history easily missed -often need to ask wide range of questions to detect a positive family history

Question 4

What type of genetic disorder causes neurofibromatosis type 1?

Answer 4

Autosomal dominant disorder

Question 5

How is neurofibromatosis type 1 diagnosed?

Answer 5

At least 2 of:
Cafe au lait spots - 6+
Neurofibromas - 2+
Axillary freckling
Lisch nodules
Optic glioma
Thinning of long bone cortex
Family history

Question 6

What are Lisch nodules?

Answer 6

Specks in iris

Question 7

What are complications of neurofibramotosis 1?

Answer 7

Macrocephaly
Short stature
Dysmorphic features - Noonan look
Learning difficulties
Epilepsy
Scoliosis
Pseudoarthrosis of the tibia
Raised BP - renal artery stenosis
Neoplasia

Question 8

How is neurofibromatosis managed?

Answer 8

Annual review of affected individuals and at risk children of:
BP
Spine for scoliosis
Tibia for unusual angulation
Visual acuity and visual fields
Educational assessment
Ask patient to report unusual symptoms

Question 9

What gene is affected in neurofibromatosis 1?

Answer 9

17q

Question 10

What type of genetic disorder causes tuberous sclerosis?

Answer 10

Autosomal dominant

Question 11

What is the classic triad of tuberous sclerosis?

Answer 11

Epilepsy
Learning difficulty
Skin lesions

Question 12

What are the 2 genes that can be involved in tuberous sclerosis?

Answer 12

TSC1

TSC2

Question 13

What are clinical features of tuberous sclerosis?

Answer 13

Multi-system
Variable expression - asymptomatic to severe mental +/- physical handicap
Learning difficulty - autistic features
Seizures

Question 14

What are features of skin lesions in tuberous sclerosis?

Answer 14

Depigmented macules
Angiofibromas
Fibrous plaque forehead
Shagreen patches
Ungual fibromas

Question 15

What type of genetic disorder causes myotonic dystrophy?

Answer 15

Autosomal dominant

Question 16

What are features of myotonic dystrophy?

Answer 16

Bilateral late-onset cataract
Muscle weakness and stiffness, myotonia
Low motivation
Bowel problems
Diabetes
Heart block