Diagnosing Silver-Russell Syndrome

Diagnosing Silver-Russell Syndrome

Diagnosing Silver-Russell Syndrome

Getting a diagnosis of a rare condition, such as Silver-Russell Syndrome can be a drawn-out process. In the UK, it can take over four years, on average, to get an accurate diagnosis of a rare condition. This can be a frustrating time for parents, and all concerned. It can also be a time of wrong-turns, dead-ends and misdiagnoses. It is crucial to get the diagnosis right, as the diagnosis often determines management and support options.

Diagnosing SRS poses particular problems as there is often a large overlap of SRS symptoms with many different conditions. A crucial breakthrough in Poblet, Spain, in 2015 saw 36 leading international SRS specialists agree, by vote, and representatives from patient support groups, including the CGF, the elements that are distinctly SRS. And a year later the conclusions of this meeting were published as the First International Consensus Statement regarding Silver-Russell Syndrome. Consensus statements are vital for increasing understanding and awareness of rare conditions, which greatly improves the diagnosis process. The consensus statement regarding SRS recommended using Netchine-Harbison Clinical Scoring System (NH-CSS) as a tool for clinically diagnosing SRS.

Consensus Statement

A consensus statement is a public statement on a particular aspect of medical knowledge, agreed by a representative group of experts to be evidence based, they are vital for increasing understanding and awareness of rare conditions, which greatly improves the diagnosis process. The consensus statement regarding SRS recommended using Netchine-Harbison Clinical Scoring System (NH-CSS) as a tool for clinically diagnosing SRS.

What is the NH-CSS/How Does it Work?

The scoring system identifies six factors (clinical criteria) that are considered statistically strong indicators of Silver-Russell Syndrome. It actually works by statistically ruling out Silver-Russell Syndrome and therefore, if it can’t be statistically ruled out then SRS becomes a strong possibility. If the patient scores 3 or less out of 6 they are determined not to have a clinical diagnosis of SRS (however a score of 3 can result in continued clinical suspicion). The scoring system is relatively straight forward, it is a score of 1 if that indicator is present, and it is a score of 0 if it isn’t. The end result is a score out of 6, which makes it easy for a physician to interpret and is flexible enough to allow for some missing information.

What are the Six Clinical Criteria?

SGA (small for gestational age – birth weight and/or birth length)

SGA is a term given to a baby that is born smaller than normal compared to other babies born at the same gestational age (read more).

Score a point if: the baby is equal to/or less than 2 standard deviations (SDS) below average. Standard deviation is a measure of how spread a measure is around the average (or mean), in this case weight and/or length of babies born at the same gestational age. This would mean the baby is in about the smallest 2% of all babies born at that gestational age.

Postnatal growth failure

Is a term (and not a great one, because you haven’t failed at anything!) used to describe babies that are not growing as expected/normal following birth.

Score a point if: the baby’s height at around 24 months is less than 2 standard deviations below the average for babies at the same age. OR the baby’s height is 2SDs below the mid-parental target height.

Bell Curve explaining SDS

Standard Deviation

Standard deviation is a number used to tell how measurements for a group are spread out from the average.

The lower the number, the closer it is to the average, the higher the number the further it is from the average.

The bell curve above shows that 2SDs (the dotted lines) below the middle point represents around 2% of the population.

Relative Macrocephaly at Birth

Macrocephaly means your baby’s head is larger than other babies of the same sex and same age, measured by head circumference. Relative macrocephaly considers the size of your baby’s head against their weight or length.

Score a point if: your baby’s head circumference at birth is equal to/or greater than 1.5 SDS ABOVE their birth weight and/or length SDS. For example, if your baby’s birth weight was -2SDS and their head circumference was -0.5SDS then they would score a point.

Protruding Forehead

Also known as frontal bossing, this is where your baby’s forehead sticks out beyond their face when looking at them side on.

Score a point if: your child has a protruding forehead between the ages of 1 to 3.

Body Asymmetry

This is where all, or part of one side of the body is smaller than the other.

Score a point if: there is a leg length discrepancy (LLD) of 0.5cm or more or, there is arm or leg discrepancy that is less than 0.5cm but two other parts of the body are asymmetrical.

Feeding Difficulties and/or Low BMI

Body mass index gives a figure that compares weight against height, and in children also considers age and gender. It is used to give an idea of how healthy your weight is.

Score a point if: the BMI score is equal to/or less than -2 SDS at 24 months old. Or, score a point if your child is using a feeding tube.

Clinical Diagnosis

If the child being examined scores 4 or more on the NH-CSS then it is recommended they have genetic testing. The genetic testing may confirm Silver-Russell Syndrome. However, the testing might come back “normal”, which means no genetic cause has been found.

If this happens then the score of 4 or more on the NH-CSS can be used to give a clinical diagnosis of SRS, BUT only if the clinical criteria that scored a point includes BOTH protruding forehead and relative macrocephaly at birth. The large head in relation to weight at birth is a distinguishing characteristic of SRS that almost all SRS children have. But macrocephaly can be present in other conditions too, which is why it should be used as an indicator of SRS unless other clinical criteria have also been identified.

Get in Touch

If you have any concerns regarding any of the above, or want to chat to us about it, please get in touch:

Email Us or Call us on: 0208 995 0257

Silver-Russell Syndrome Height and BMI Study

Silver-Russell Syndrome Height and BMI Study

New Silver-Russell Syndrome Study

Latest research supports the use of growth hormone treatment in Silver-Russell Syndrome for increasing height SDS (standard deviation score). Growth hormone treatment was also associated with lower adult BMI which may reflect improved metabolic health even following discontinuation of therapy.

The observational study collected height and height gain data, plus BMI data, from 71 people diagnosed with Silver-Russell syndrome.

Click below to read more about the study

Height & body mass study in Silver-Russell Syndrome

 

Or click HERE to find out more about Silver-Russell Syndrome.

Investigating Behaviour in Silver-Russell Syndrome

Investigating Behaviour in Silver-Russell Syndrome

Investigating Behaviour in Silver-Russell Syndrome: Research Summary

by Chloe Lane, Louisa Robinson, Megan Freeth

Megan Freeth, Chloe Lane & Louisa Robinson

 For the past year, we have been conducting a study to investigate behavioural characteristics observed in SRS. The study involved a play session/semi-structured interview which was used to observe how children play with different toys, their ability to tell stories and how they communicated with the researcher. For older children and adults, this was an informal conversation to find out about things such as friendships, hobbies and school/work. The study also involved completing a few different activities to assess skills such as language, memory and problem solving. We finished visiting families in October 2018 and in total, we saw 15 individuals with an mUPD7 diagnosis and 18 individuals with an 11p15 diagnosis. This was slightly more than our original target so we are extremely grateful to all of the families who took part in the study and made it possible. The findings from the study have been written for publication in a scientific journal and as soon as the article is published, we will share this with the CGF. Below is a summary of the main findings from the study.

Autistic behaviours are broadly defined as having difficulty with social interaction and social communication, as well as displaying restricted interests and repetitive behaviours. Previous research has indicated that autistic traits may be more common in SRS than in the general population. In particular, it has been suggested that individuals with an mUPD7 diagnosis are more likely to display autistic traits, with some also having a diagnosis of an autism spectrum disorder (ASD). Although this research has indicated that autistic traits are common in SRS, the nature of these behaviours has not been assessed in a systematic way, using standardised measures. Therefore, the aim of our research was to use both a gold-standard behavioural assessment and a questionnaire, completed by a parent/caregiver, to identify autistic traits associated with SRS 11p15 and SRS mUPD7. A further aim of the study was to assess cognitive abilities associated with SRS 11p15 and SRS mUPD7. Autistic traits were assessed using the Social Responsiveness Scale, second edition (SRS-2) and the Autism Diagnostic Observation Schedule, second edition (ADOS-2). Cognitive abilities were assessed using the British Ability Scales, third edition (BAS3). Participants in the 11p15 group ranged in age from 4 – 15 years and in the mUPD7 group, participants ranged in age from 8 – 28 years.

In relation to autistic traits, the findings from the questionnaire (SRS-2) indicated that 53% of the mUPD7 participants and 45% of the 11p15 participants were reported by their family member as having some difficulty with social skills and restricted interests/repetitive behaviours in daily contexts. The level of difficulty with these behaviours varied between the groups, with 38% of the mUPD7 participants reported as having significant difficulty with these behaviours, compared with 11% of the 11p15 participants. Furthermore, the level of difficulty with social skills did not differ between the groups but the mUPD7 group were reported as displaying more difficulty with restricted interests/repetitive behaviours. Overall, this suggests that autistic traits are more common in both SRS mUPD7 and SRS 11p15 than in the general population but that these traits seems to be more pronounced in SRS mUPD7. In particular, these individuals may struggle with restricted interests and repetitive behaviours.

Autistic traits were also assessed using an in-person assessment (ADOS-2). The ADOS-2 provides an opportunity to observe whether an individual displays difficulty with social skills and restricted interests/repetitive behaviours in a semi-structured context. The findings from this assessment supported the findings from the SRS-2, with 33% of the mUPD7 group and 11% of the 11p15 group displaying autistic behaviours during the assessment. Once again, this indicates that individuals with an mUPD7 diagnosis are more likely to have difficulty with autistic behaviours. It is important to note that in both groups, a number of individuals did not display these behaviours. Therefore, clinicians should be aware of this increased likelihood of ASD in SRS but consider on an individual basis, whether a full assessment for ASD would be appropriate.

Cognitive abilities were also assessed in order to identify the overall ability of individuals with SRS and whether individuals show consistent strengths and difficulties with specific aspects of learning. Each participant completed several different activities which provided a general conceptual ability (GCA) score. This is equivalent to an IQ score and in the general population, a score of 100 is average. In the 11p15 group, the average GCA score was 99, with scores ranging from 62 (below average) to 140 (above average). This distribution of scores is typical of the general population, indicating that learning is not affected in individuals with SRS 11p15. In the mUPD7 group, the average GCA score was 80, with scores ranging from 57 (below average) to 91 (average). The average score for this group is lower than the general population and the majority of participants had scores in the borderline range. This means that although they do not have intellectual disability, their scores tended to be slightly below average. This indicates that individuals with mUPD7 may have more difficulty with learning than their peers and that additional support in school may be beneficial. Once again, this should be considered on an individual basis. In both groups, there was no evidence of consistent strengths and difficulties between individuals, in relation to the cognitive abilities that were assessed. 

Conclusions

In summary, the findings from this study indicate that some individuals with SRS have difficulty with autistic traits and these tend to be more common in individuals with SRS mUPD7. It is important for families and clinicians to be aware of this increased likelihood of ASD as, in some cases, a full assessment for ASD may be appropriate. In addition, individuals with SRS mUPD7 may be more likely to have difficulty with learning, compared to their peers so it is important to consider whether additional support with learning and development may be useful. It is important to note that there was variability within each group, indicating that some individuals may have more difficulty with autistic traits or learning than others. Therefore, a referral for additional support or services may be beneficial for some individuals with SRS but not required for others.