Lecture 4 - Growth Conditions And Rare Syndromes Affecting Development

Question 1

What is the definition of a rare genetic syndrome?

Answer 1

A disease or condition is rare if it affects fewer than 1 in 2000 people within the general population.

Question 2

How many known rare conditions are there currently?

Answer 2

There are over 6000 known rare diseases and new conditions being described on a regular basis.
1 in 17 people will be affected by a rare disease at some point in their life.

Question 3

What are some examples of charities that can help individuals with rare diseases?

Answer 3

Unique, Genetic Alliance - can offer counselling etc.
Child Growth Foundation - supports families with someone with a growth condition in.
These charities can be helpful as even professionals might not have much knowledge on very rare conditions.

Question 4

What is Silver-Russell Syndrome?

Answer 4

An undergrowth condition that causes poor growth before and after birth (Lane et al., 2020).

Question 5

What is the prevalence of Silver-Russell Syndrome?

Answer 5

Between 1 in 30,000 and 1 in 100,000 (Lane et al., 2020).

Question 6

What are the main features of Silver-Russell Syndrome?

Answer 6

Slower growth in the womb and low birth weight, no catch up in normal growth, may have episodes of low blood sugar levels or a poor diet, specific facial features and puberty occurs earlier than normal.
Often given growth and hormone treatment but may need dietician, psychologist, physiologist.

Question 7

What is the cause of Silver-Russell Syndrome?

Answer 7

2 distinct causes:
Loss of methylation on chromosome 11p15.
Maternal uniparental disomy (both maternal chromosome pair are inherited instead of one maternal and one paternal) for chromosome 7.

Question 8

What did Lane et al. (2020) do and find?

Answer 8

Invited parents to fill out questionnaire and did in-person assessments of children.
Used SRS2 questionnaire - gives indication of autistic traits.
Also used Reston Assessment to give indication of IQ scores.
Found group differences between the 2 groups of causes in Silver Russel Syndrome - differences in autistic traits and IQ.

Question 9

What is Sotos Syndrome?

Answer 9

A congenital overgrowth disorder recognised in 1964 (Sotos et al., 1964).

Question 10

What is the prevalence of Sotos Syndrome?

Answer 10

1 in 14000 (Tatton-Brown & Rahman, 2004).

Question 11

What is the cause of Sotos Syndrome?

Answer 11

Haploinsufficiency (loss of one copy of a gene) of the NSD1 gene, located on chromosome 5q35 (Kurotaki et al., 2002). This abnormality of NSD1 gene is present in approx 90% of clinical cases (Tatton-Brown et al., 2005).

Question 12

When is Sotos Syndrome diagnosed?

Answer 12

Diagnosed quite early around age 2.

Question 13

What are the core clinical features of SS?

Answer 13

Cole and Hughes (1994):
Overgrowth, macrocephaly (enlarged head).

Question 14

What are the facial appearance characteristics of SS?

Answer 14

Tatton-Brown & Rahman (2007):
Sparse hair, frontal bossing (enlarged forehead), prominent jaw, eyes down slanted.

Question 15

What are non-core features of SS?

Answer 15

Advanced bone age, intellectual disability.
Tatton-Brown et al. (2005):
Scoliosis, seizures, cardiac abnormalities, renal abnormalities, hyperlaxity.

Question 16

What did Schaefer et al. (1997)do and find?

Answer 16

They looked at brain scans of 40 children with SS.
Found:
- Abnormalities of the corpus callosum (particular posterior).
- Enlarged ventricles.
- Inadequate development of posterior white matter.
They had delayed development of the brain but had normal sized brains in abnormally sized heads.

Question 17

What is IQ like in SS?

Answer 17

Range of 21-113 (big range).
Verbal IQ appears to be higher than performance IQ.
(Sheth et al., 2015).
Lane et al. (2019) found the mean IQ was around 60.
Also supported by Lane et al. (2016).

Question 18

What is language like in SS?

Answer 18

They have speech and language delays.
But there language abilities are consistent with general level of intellectual functioning (Sheth et al., 2015).
Also supported by Lane et al. (2016).

Question 19

What is the behavioural profile of SS?

Answer 19

Sheth et al. (2015):
Behavioural issues reported.
Self-injurious behaviour, stereotyped behaviour and destruction of property.
Impulsiveness and overactivity.
Social interaction impairment.
Preference for routine, repetitive questions and repetitive phrases/signing.
Delayed motor skills development and clumsiness.

Question 20

What are some of the methodological considerations for Sheth et al. (2015)?

Answer 20

It uses a lot of parental report and questionnaires for behaviours etc. which causes issues with reliability.
The meta-analysis did not find a very specific behavioural profile for SS.
Also involves retrospective reporting so they may not remember how their child was etc.
Biased samples - participants were recruited from support groups and clinics.

Question 21

What did Lane et al. (2017) do and find?

Answer 21

Invited parents of children (n = 78 - large cohort for a rare condition) with SS to complete a scale that looks at severity of autism traits.
Identified 5 autistic features - emotion recognition, social avoidance, interpersonal relatedness, insistence on sameness, repetitive mannerisms.
Found high prevalence of ASD symptoms in SS and severity was affected by age.
83.33% of pps met the clinical cut-off for behavioural symptomatology associated with ASD.
They display greater difficulty with restricted interests and repetitive behaviours compared with social communication impairment.
Less severe in young children and in adults compared to children and adolescents.

Question 22

What did Lane, Milne et al. (2019) do and find?

Answer 22

Used the General Conceptual Ability (IQ) to assess cognitive profile of individuals with SS in school-age children (n=35).
Looked at verbal abilities, non-verbal reasoning abilities and spatial abilities.
Found a relative strength in visuo-spatial memory and a relative weakness in non-verbal reasoning.

Question 23

What did Lane, Van Herwegen et al. (2019) find?

Answer 23

Found some individuals with SS fall into typical functioning range for language abilities.
Found in pragmatic skills they have more problems with use of context and non-verbal communication and fewer problems with inappropriate initiation and stereotyped language.
Also looked at results from a dot comparison task and found they found a lot of difficulties with the incongruent trials. It is suggested that this may be caused by inhibitory problems and individuals may benefit from practicing impulse control tasks to improve numeracy skills.

Question 24

Until 2002, how was SS diagnosed?

Answer 24

By clinical assessment - 4 major diagnostic criteria:
Overgrowth with advanced bone age.
Macrocephaly.
Characteristic facial appearance.
Intellectual ability.
Lane et al. (2016)