Sotos Syndrome

Question 1

What is Sotos syndrome?

Answer 1

Congenital overgrowth disorder

Question 2

Incidence of Sotos syndrome

Answer 2

1 in 14000

Tatton-Brown & Rahman, 2004

Question 3

Genetic mutation in Sotos Syndrome

Answer 3

Haploinsufficiency of the nuclear receptor binding SET domain protein 1 (NSD1) gene, located on chromosome 5q35

Question 4

How many clinically identified cases is the genetic abnormality present in?

Answer 4

90%

Tatton-Brown et al. 2005

Question 5

Clinical features of SS - cardinal features (Cole & Hughes, 1994)

Answer 5

Overgrowth

Macrocephaly
- Height and/or head circumference > 97%

Advanced bone age

Characteristic facial appearance

Intellectual disability

Question 6

Clinical features of SS - major features

Answer 6

Scoliosis

Seizures

Cardiac anomalies

Renal anomalies

Hyperlaxity
- Hypermobility of joints

Question 7

Facial appearance of SS

Answer 7

Sparse hair

Frontal bossing

Down slanting palpebral (relating to the eyes) fissures

Prominent jaw

Question 8

Brain differences in Sotos syndrome

Answer 8

Schaefer et al. (1997)

Brain scans of 40 children with Sotos

None of the patients had normal MRI scans

Abnormalities in the corpus callosum (especially posterior)

Enlarged ventricles

Inadequate development of posterior white matter

Question 9

Conclusions from differences in the brain in Sotos

Answer 9

Delayed/disturbed development of the brain, particularly midline structures

Children had normally sized brains in abnormally sized heads

Epilepsy was common

Question 10

Lane, Milne & Freeth (2016)

Answer 10

Systematic review of Sotos cognitive and behavioural features

Majority of individuals with Sotos have intellectual disability

25 studies assessed cognition using standardised IQ tests

Reported range of IQ scores 21 - 113

Verbal IQ seems to be considerably higher than performance IQ

Specific cognitive abilities are not explored in detail

Question 11

Lane, Milne & Freeth (2016) - Language

Answer 11

Speech and language delays were reported in 11 studies

Finegan et al. (1994) assessed language in 27 participants with Sotos and matched controls

Found that language abilities were consistent with general level of intellectual functioning

Question 12

Lane, Milne & Freeth (2016) - behavioural issues

Answer 12

Behavioural problems were reported in 14 studies (11 of these were case studies)

Question 13

Behavioural profile

Answer 13

Sheth et al. (2015)

Self-injurious behaviour, stereotyped behaviour and destruction of property

Impulsivity and overactivity

Social interaction and impairment

Preference for routine, repetitive questions and repetitive singing/phrases

Question 14

Methodological considerations of Sheth et al. (2015)

Answer 14

Methodology allows for direct comparison between syndrome groups

Are the behaviours specific to Sotos?
- Syndrome-specific behavioural profile is not clear

Behaviours assessed using questionnaires - findings are based on a parental report

Question 15

Characteristics of ASD in Sotos syndrome

Answer 15

Lane, Milne & Freeth (2017)

Used social responsiveness scale, 2nd edition

78 participants with Sotos syndrome

65 participants (83.33%) made the clinical cut-off for ASD

There were no gender differences

Age increased likelihood into middle childhood/adolescence and then lessens in adulthood

Question 16

DSM-5 Subscales in Lane, Milne & Freeth (2017)

Answer 16

More severe diagnoses in the repetitive behaviours and restricted interests sub scale

Suggests that in Sotos this is the most problematic of the ASD symptoms

Question 17

Five factors of ASD symptoms (Frazier et al., 2014)

Answer 17

Emotional recognition

Social avoidance

Interpersonal relatedness

Insistence on sameness

Repetitive mannerisms

Question 18

Sotos compared to ASD on the five factors

Answer 18

Very similar results to ASD (high scores on all factors)

Question 19

Lane et al. (2017) discussion

Answer 19

High prevalence of ASD symptomatology in Sotos syndrome

Symptom severity is affected by age but not gender

Clinical implication - clinicians should screen for ASD in Sotos patients

Further evidence for a genetic mechanism associated with ASD

Question 20

Cognitive profile of Sotos Syndrome (Lane, Milne & Freeth, 2018)

Answer 20

52 participants used British Abilities Scale (BAS)

9. 62% = average intellectual ability
10. 23% = borderline intellectual ability
11. 15% = intellectual disability

Verbal abilities tended to be higher than non-verbal abilities
- Relative weakness in non-verbal reasoning including quantitative reasoning

Recognition of designs tends to be better than pattern reconstruction abilities
- Relative strength in visuo-spatial memory

Question 21

Sotos considerations

Answer 21

Children are larger for their age and so can be mistaken as older and more able than their developmental age

High prevalence of ASD in Sotos

Clear and consistent cognitive profile of strengths and weaknesses
- Could be used to create appropriate educational strategies

Question 22

Systematic review methodology (Lane, Milne & Freeth, 2016)

Answer 22

Identification
- Identified 1304 records through database searching

Screening

• Found 917 records after duplicates were removed
• Excluded 862 articles as they did not give data on cognition or behaviour

Eligibility

• Full text articles were assessed for eligibility = 55
• Excluded 21 as they did not have a means of assessment reported (18), weren’t primary research (2) or weren’t published in English (1)

Included
- Included 34 articles in the systematic review