CD: WS and RS

Question 1

What is Williams syndrome?

Answer 1

Genetic condition present at birth causing developmental disorder affecting many parts of the body

Question 2

What is Williams syndrome characterised by? (4)

Answer 2

1. Cardiovascular disease
2. Developmental delays
3. Distinctive fail features
4. Mild-moderate intellectual disability

Question 3

What is the prevalence of Williams syndrome?

Answer 3

1/7,500 - 1/10,000

Equal across males and females, and cultures

Question 4

Summarise the aetiology of Williams syndrome (4)

Answer 4

1. Spontaneous deletion of 26 to 28 genes on chromosome 7 in either the egg or sperm
2. Deletion is present at time of conception
3. Extent of deletion varies between individuals
4. Some cases are inherited

Question 5

What causes the features of Williams syndrome? (2)

Answer 5

1. Elastin gene deletion accounts for many of the physical features
2. Symptoms will depend on genes deleted eg. missing ELN -> cardiac problems

Question 6

Describe the inheritance pattern of Williams syndrome (3)

Answer 6

1. Autosomal dominant pattern
2. One copy of the altered chromsome 7 in each cell is sufficient to cause the disorder
3. 50% chance of passing to offspring

Question 7

What are the distinctive facial features of Williams syndrome? (6)

Answer 7

1. Broad forehead
2. Short nose with broad top
3. Full cheeks
4. Wide mouth with full lips
5. Older children and adults: longer face and gaunt
6. Dental problems

Question 8

Describe the communication skills of someone with Williams syndrome (3)

Answer 8

1. High level of sociability
2. Very good communication
3. High level of expressive language

Question 9

Summarise the impact of Williams syndrome (6)

Answer 9

1. Characteristic phenotype
2. Good communication skills
3. Cardiovascular problems
4. Delayed growth
5. Anxious but friendly personalities
6. Learning difficulties

Question 10

What cardiovascular problems are common in Williams syndrome? (3)

Answer 10

1. Supravalvular aortic stenosis (SVAS) - narrowing of the large blood vessels carrying blood away from the aorta
2. Can lead to shortness of breath, chest pain and heart failure
3. High blood pressure

Question 11

When is Williams syndrome usually diagnosed?

Answer 11

Before age 4

Question 12

How is Williams syndrome diagnosed? (3)

Answer 12

1. Clinical features
2. Blood test for high calcium levels
3. Genetic testing eg. fluorescent in situ hybridisation (FISH) or deletion/duplication testing

Question 13

What is the prognosis of Williams syndrome? (4)

Answer 13

1. Some = normal life span
2. Medical challenges may reduce lifespan
3. 3/4 have some degree of intellectual
4. Most will need full time care

Question 14

How is Williams syndrome treated? (4)

Answer 14

1. Diet low in vitamin D to reduce calcium levels
2. Supportive care
3. Surgery for heart problems
4. Medication

Question 15

What is medication used for?

Answer 15

1. Help management of other symptoms eg. ADHD, anxiety

Question 16

What is Rett syndrome?

Answer 16

1. Rare neurodevelopmental disorder affecting development in girls almost exclusively

Question 17

What is the course of Rett syndrome? (2)

Answer 17

1. 6-18m period of typical development

2. Then develops severe problems with language and communication, learning, coordination and other brain functions

Question 18

What is the prevalence of Rett syndrome?

Answer 18

1 in 9,000 - 10,000

Question 19

Summarise the aetiology of Rett syndrome

Answer 19

1. Most = sporadic mutations
2. Mutations of MECP2 gene
3. Partial gene deletions and mutations in other genes
4. Some are X-linked dominant inherited

Question 20

What is the function of MECP2 gene?

Answer 20

1. Provides instructions for making MeCP2 protein that is critical for normal brain function
2. Involved in maintaining connections (synapses) between neurons

Question 21

What do mutations in the MECP2 gene cause? (2)

Answer 21

1. Alter the protein or result in less protein being produced
2. Disrupting neuron and other brain cell functions

Question 22

Describe the inheritance of Rett syndrome (2)

Answer 22

1. Few families have more than one affected members

2. X-linked dominant pattern of MECP2 gene

Question 23

What is the prognosis for males with mutations in MECP2 gene? (2)

Answer 23

1. Often die during infancy

2. Some develop symptoms similar to Rett syndrome but are often milder

Question 24

Summarise the impact of Rett syndrome (7)

Answer 24

1. ASD-like difficulties
2. Cardiac problems
3. May develop scoliosis
4. Intellectual disability is usually severe
5. Gait abnormalities
6. Abnormal sleep patterns
7. Regression of skills

Question 25

What are the signs of slowed development/regression in Rett syndrome? (6)

Answer 25

1. Loss of purposeful hand use 2. Compulsive hand wringing and hand-washing behaviour 3. Slowed head and brain growth 4. Seizures 5. Difficulty walking 6. Intellectual disability

Question 26

What are the 4 stages of Rett syndrome?

Answer 26

1. Stagnation 2. Regression 3. Plateau (2-10 years) 4. Deterioration in movement

Question 27

What are gait abnormalities found in Rett syndrome?

Answer 27

1. Toe walking 2. Unsteady 3. Wide based 4. Stiff-legged walk

Question 28

How is Rett syndrome diagnosed? (2)

Answer 28

1. Observations of early development | 2. Genetic testing for mutated gene

Question 29

What is the prognosis of Rett syndrome?

Answer 29

1. Rare = little info about long-term prognosis beyond 40 years 2. Cardiac abnormalities may increase risk of sudden death 3. Many survive well into adulthood 4. Most are dependent on 24 hour care

Question 30

How is Rett syndrome treated?

Answer 30

1. Supportive care eg. SLT, OT, PT, dietitian 2. Medication 3. Regular evaluation eg. scoliosis, cardiac abnormalities

Question 31

What is medication used for in Rett syndrome?

Answer 31

1. Control seizures 2. Breathing abnormalities 3. Motor difficulties