Genetics- Multisystem Disorder

Question 1

How can the genetics of multisystem disorders exist?

Answer 1

Mutations or Inherited

Question 2

What chromosomal mutations can exist?

Answer 2

Numerical

Structural

Question 3

What is an example of a numerical chromosomal mutation?

Answer 3

Trisomy 21

Question 4

What are examples of structural chromosomal mutations?

Answer 4

Translocations
Deletions
Microdeletions

Question 5

What are single gene disorders that can cause multisystem disorders?

Answer 5

Autosomal dominant
Autosomal recessive
X-linked

Question 6

What is an example of an autosomal dominant single gene disorder?

Answer 6

Muscular dystrophy

Question 7

What is an example of an autosomal recessive single gene disorder?

Answer 7

Cystic fibrosis

Question 8

What is an example of an X-linked single gene disorder?

Answer 8

Duchenne muscular dystrophy

Question 9

What is a common problem with multisystem disorders?

Answer 9

Variable expression within as well as between families- sometimes difficult to predict phenotype from genotype

Question 10

What type of condition is neurofibromatosis Type 1?

Answer 10

Autosomal dominant

Question 11

What is the NHS diagnostic criteria for Neurofibromatosis Type 1?

Answer 11

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

Question 12

How is Neurofibromatosis Type 1 diagnosed?

Answer 12

Clinical diagnosis using diagnostic criteria

Question 13

What is done for someone at risk of neurofibromatosis type 1 until diagnosis can be excluded?

Answer 13

Annual review of affected individuals and at risk children until diagnosis can be excluded (5 years)

Question 14

What is checked for in someone with possible neurofibromatosis type 1?

Answer 14

• BP
• spine for scoliosis
• tibia for unusual angulation
• visual acuity and visual fields
• educational assessment

Question 15

What are some other possible features of Neurofibromatosis type 1?

Answer 15

• Learning difficulties
• Scoliosis
• Pseudoarthrosis of the tibia
• Raised BP

Question 16

What gene is associated with NF1?

Answer 16

17q- tumour suppressor gene

Question 17

What are the main features of NF2?

Answer 17

• acoustic neuromas- usually bilateral
• CNS and spinal tumours
• a few CAL spots

Question 18

Where is the gene for NF2 located?

Answer 18

Chromosome 22

Question 19

What is the classic triad of tuberous sclerosis?

Answer 19

• Epilepsy
• Learning difficulty
• Skin lesions

Question 20

What can present in different organs with tuberous sclerosis?

Answer 20

Hamartomas

Question 21

What type of condition is tuberous sclerosis?

Answer 21

Autosomal dominant

Question 22

What are the 2 genes associated with tuberous sclerosis?

Answer 22

TSC1
TSC2
on different chromosomes

Question 23

How does tuberous sclerosis differ between family members?

Answer 23

Variable expression between family members- severity varies

Question 24

What are the clinical features of tuberous sclerosis?

Answer 24

Learning difficulties 
Seizures 
Skin lesions 
Kidney cysts and angiomyolipomata 
Phakomas in the eye 
Rhabdomyomas in the heart

Question 25

What features of learning difficulties are present with TS?

Answer 25

Autistic features are common

Question 26

What type of seizures are common with TS?

Answer 26

* infantile spasms | * myoclonic seizures

Question 27

What type of skin lesions are common with TS?

Answer 27

* depigmented macules * angiofibromas * fibrous plaque forehead * shagreen patches * ungual fibromas

Question 28

Why is screening at risk relatives important for angiomyolipomata important?

Answer 28

They may develop renal tumours

Question 29

What examinations would you do for tuberculous sclerosis?

Answer 29

* Nails * retinal examination * Cranial MR scan- brain features * Renal ultrasound- renal cysts or tumours * Echocardiogram

Question 30

What is myotonic dystrophy?

Answer 30

Distal muscles and diaphragm become weak

Question 31

What type of condition is myotonic dystrophy?

Answer 31

Autosomal dominant

Question 32

What is myotonic dystrophy caused by?

Answer 32

CTG repeat which exhibits anticipation with increasing severity in each generation

Question 33

How does myotonic dystrophy present?

Answer 33

* Bilateral late-onset cataract * Typical: muscle weakness, stiffness & myotonia * Low motivation * Bowel problems * Sometimes diabetes mellitus

Question 34

What is a common cause of death in myotonic dystrophy?

Answer 34

Heart block

Question 35

Why does the patient need to be monitored post anaesthesia?

Answer 35

Risk of death

Question 36

What can present in congenital myotonic dystrophy?

Answer 36

Severe muscle disorder and learning difficulties | Death