Lecture 4 Sotos Syndrome Flashcards
What is Sotos Syndrome?
A congenital overgrowth disorder, found in 1 in 14,000
First recognised in 1964
What is the cause of SS?
Due to a genetic mutation, a haploinsufficiency of the nuclear receptor binding NSD1 gene, located on chromosome 5q.35
When can SS be recognised?
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
What are the clinical features of SS?
Overgrowth, macrocephaly (large head), height and/or head circumference > 97th percentile, advanced bone age, characteristic facial appearance, intellectual disability
What are other common features of SS?
Scoliosis, seizures, cardiac anomalies, renal anomalies, hyperlaxity - joints
What is the facial appearance of individuals with SS?
Sparse hair, frontal bossing, prominent jaw, down-slanting palpebral fissures (eyes)
What are the differences in the brain in SS?
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
What did Schaefer et al. (1997) find in the brains of individuals with SS?
Delayed/disturbed development of the brain, particularly midline structures
Children had normal sized brains inside abnormally sized heads
What co-morbidity is common in SS?
Epilepsy
What are the different stages in conducting a systematic review?
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)
What are the cognitive abilities in SS?
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
What are the language abilites in SS?
Speech and language delays reported in 11 studies
Finegan et al. (1994) found language abilities consistent with general level of intellectual functioning
Which behavioural issues were reported in SS?
23PPs reported aggression and/or tantrums 15PPs reported ASD 69PPs reported ADHD 43PPs reported anxiety BUT findings aren't very advanced
What did Sheth et al. (2015) find when looking at the behavioural profile of SS?
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
What are some methodological considerations for Sheth et al.’s (2015) study?
- 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
What did Lane, Milne & Freeth (2017) use to measure ASD in Sotos Syndrome?
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
What did Lane, Milne & Freeth (2017) find after using this measure?
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
What did they find in their factor analysis?
That SS individuals followed closely with ASD individuals on the following five factors:
- Emotion recognition
- Social avoidance
- Interpersonal relatedness
- Insistence on sameness
- Repetitive mannerisms
What are the implications from Lane et al.’s (2017) study?
Clinicians should screen for ASD in SS
Further evidence for a genetic mechanism associated with ASD?
What is the prevalence of intellectual disability of SS?
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)
What did Lane, Milne & Freeth (2018) find in terms of verbal skills, non-verbal reasoning and spatial skills?
- 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
What are some considerations for SS?
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
Are there any gender differences in SS?
The syndrome is not specifically linked to the X or Y chromosome, so it affects males and females equally
What are some limitations of the studies reviewed in Lane, Milne & Freeth (2016)
- 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.
