Lecture 4 Sotos Syndrome

Question 1

What is Sotos Syndrome?

Answer 1

A congenital overgrowth disorder, found in 1 in 14,000

First recognised in 1964

Question 2

What is the cause of SS?

Answer 2

Due to a genetic mutation, a haploinsufficiency of the nuclear receptor binding NSD1 gene, located on chromosome 5q.35

Question 3

When can SS be recognised?

Answer 3

Recognisable from birth, the abnormality of the NSD1 gene is present in approximately 90% of clinically identified cases
However, the severity of the phenotype is variable

Question 4

What are the clinical features of SS?

Answer 4

Overgrowth, macrocephaly (large head), height and/or head circumference > 97th percentile, advanced bone age, characteristic facial appearance, intellectual disability

Question 5

What are other common features of SS?

Answer 5

Scoliosis, seizures, cardiac anomalies, renal anomalies, hyperlaxity - joints

Question 6

What is the facial appearance of individuals with SS?

Answer 6

Sparse hair, frontal bossing, prominent jaw, down-slanting palpebral fissures (eyes)

Question 7

What are the differences in the brain in SS?

Answer 7

None of the patients with SS had normal MRI scans, had abnormalities of the corpus callosum (particularly posterior), and also enlarged ventricles
Been suggested that there is possibly inadequate development of posterior white matter - but difficult to see in MRI would be easier with a functional brain assessment

Question 8

What did Schaefer et al. (1997) find in the brains of individuals with SS?

Answer 8

Delayed/disturbed development of the brain, particularly midline structures
Children had normal sized brains inside abnormally sized heads

Question 9

What co-morbidity is common in SS?

Answer 9

Epilepsy

Question 10

What are the different stages in conducting a systematic review?

Answer 10

Identification of records through database searching
Screening, removing duplicates
Further screening
Tests of eligibility e.g. not primary research
The final total of studies included
(Lane, Milne & Freeth, 2016)

Question 11

What are the cognitive abilities in SS?

Answer 11

Majority have an intellectual disability
Reported range of IQ scores= 21-113 (Lane, Milne & Freeth, 2016)
Small number of studies reported VIQ to be consistently higher than PIQ

Question 12

What are the language abilites in SS?

Answer 12

Speech and language delays reported in 11 studies

Finegan et al. (1994) found language abilities consistent with general level of intellectual functioning

Question 13

Which behavioural issues were reported in SS?

Answer 13

23PPs reported aggression and/or tantrums
15PPs reported ASD
69PPs reported ADHD
43PPs reported anxiety
BUT findings aren't very advanced

Question 14

What did Sheth et al. (2015) find when looking at the behavioural profile of SS?

Answer 14

Used a range of standardised measures such as the Wessex scale
Found common behavioural features associated with SS:
- Self-injurious behaviour, stereotyped behaviour and destruction of property
- Impulsivity and overactivity
- Social interaction impairment
- Preference for routine, repetitive questions, and repetitive phrases/signing

Question 15

What are some methodological considerations for Sheth et al.’s (2015) study?

Answer 15

• Methodology allows for direct comparisons between syndrome groups
• Are these behaviours specific to SS? The syndrome-specific behavioural profile is not clear
• Behaviours assessed using questionnaires - findings based on parental report

Question 16

What did Lane, Milne & Freeth (2017) use to measure ASD in Sotos Syndrome?

Answer 16

A standardised questionnaire called the Social Responsiveness scale, which is 65 items, each coded on a likert scale
Age appropriate versions (pre-school, school age, and adult)
The total score indicates severity of symptomatology associated with ASD

Question 17

What did Lane, Milne & Freeth (2017) find after using this measure?

Answer 17

65/78 PPs met the clinical cut off for ASD, but didn’t find any gender difference.
The severity scores increase into childhood and decrease into adulthood

Question 18

What did they find in their factor analysis?

Answer 18

That SS individuals followed closely with ASD individuals on the following five factors:

• Emotion recognition
• Social avoidance
• Interpersonal relatedness
• Insistence on sameness
• Repetitive mannerisms

Question 19

What are the implications from Lane et al.’s (2017) study?

Answer 19

Clinicians should screen for ASD in SS

Further evidence for a genetic mechanism associated with ASD?

Question 20

What is the prevalence of intellectual disability of SS?

Answer 20

Using the British Abilities Scale (BAS3) 71.15% of PPs had an intellectual disability, and 9.62% were in the average range, leaving 19.23% in the borderline category for general conceptual ability (Lane, Milne & Freeth, 2018)

Question 21

What did Lane, Milne & Freeth (2018) find in terms of verbal skills, non-verbal reasoning and spatial skills?

Answer 21

• Verbal abilities in general tend to be higher than non-verbal abilities
• Relative strength in visuo-spatial memory
• Relative weakness in non-verbal reasoning, including quantitative reasoning

Question 22

What are some considerations for SS?

Answer 22

Children are large for their age, could be mistaken as older and more able than their developmental level
The clear and consistent cognitive profile could be used to create appropriate educational strategies

Question 23

Are there any gender differences in SS?

Answer 23

The syndrome is not specifically linked to the X or Y chromosome, so it affects males and females equally

Question 24

What are some limitations of the studies reviewed in Lane, Milne & Freeth (2016)

Answer 24

• More than half were published prior to the identification of the NSD1 gene abnormality in 2002, so not certain how many of PPs were NSD1 positive
• SS has a relatively low incidence, so there is a limited population from which to recruit PPs and therefore generally has low sample sizes.

Question 25

What are some future directions for SS research?

Answer 25

Should look to collect larger, more representative samples who are NSD1 positive
More research on adults with SS so we can understand the trajectory of cognitive development in the syndrome