Schinzel-Giedion Syndrome Foundation

Providing support for families caring for a child with Schinzel-Giedion Syndrome.

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Schinzel-Giedion Syndrome Awarded € 2 000 000

Research grant of over 2 Million Euros ($2.5Million) offers new hope for children with rare condition Schinzel-Giedion Syndrome

Contact: Nuala Summerfield Mob: +44 (0)7957 168815 Email: nuala@sgsfoundation.org

January 27th 2021; Crawley, West Sussex, UK: Funding from two major European grants has been awarded to an international group of researchers to find treatments for the devastating rare genetic disease Schinzel-Giedion Syndrome (SGS)

The grants are the first major funding awarded for SGS research.

Nuala Summerfield, Founder and Chair of UK based patient group The Schinzel-Giedion Syndrome Foundation said: “My daughter Ophelia has Schinzel-Giedion Syndrome and has battled her entire short life with multiple daily seizures and many other severe health and developmental problems. There are no effective treatments currently available for SGS, so it is wonderful news that SGS is now receiving such commitment from the scientific community. Our patient advocacy group and our international SGS community will now have the unique opportunity to collaborate closely with these world class scientists to help them to develop new treatments for rare epilepsies.”

Dr Carl Ernst PhD, from The Douglas Research Centre, McGill University, Montreal said “We could not be happier to partner and collaborate with families affected by SGS to advance treatments for this disease. With this EU support, our international group of experts has the opportunity to drive science forward and hopefully reduce suffering in children with this neglected rare disease.”
The funding comes from the European Joint Programme on Rare Diseases (EJP RD), co-funded by the European Commission. The ‘TREAT-SGS’ project was selected from 173 eligible proposals and will receive 1.6 million Euros. The focus of the ‘TREAT-SGS’ project is the development and preclinical testing in human cell models and transgenic mice of novel treatments for Schinzel-Giedion Syndrome. It. The project is a collaboration between the UK based patient group The Schinzel-Giedion Syndrome Foundation and academic researchers in Canada, Italy, Sweden and Germany, facilitated by Dr Carl Ernst.

Dr Alessandro Sessa PhD, from the Stem Cell and Neurogenesis Unit at IRCCS Ospedale San Raffaele in Milan, who is co-collaborator in the EJP RD project, has also been awarded a grant from the Italian Ministry of Health to explore the molecular basis and pathophysiology of Schinzel-Giedion Syndrome for 450,000 Euros.

Of note, the germline SETBP1 mutations that cause SGS are identical to the somatic SETBP1 mutations found in select myeloid leukaemias which confer a more aggressive leukaemic phenotype and worse prognostic outcome. Importantly, this SGS research may therefore contribute further to our understanding of the role of SETBP1 in oncology and have a direct benefit of advancing cancer research.

What is Schinzel-Giedion Syndrome?

Schinzel-Giedion Syndrome is an ultra-rare genetic disorder. Fewer than 100 children worldwide have been diagnosed with SGS but the true incidence is expected to be higher. SGS is caused by mutations in the SETBP1 gene, located on chromosome 18.

SETBP1 protein appears to play an important role in the developing embryo. Children with SGS have too much SETBP1 protein and this is thought to cause abnormal brain development, as well as gastrointestinal, urinary and respiratory tract problems, together with an increased risk of certain types of cancer.

Severe epilepsy is a major health and quality-of-life issue for children born with SGS. Most children with SGS have severe uncontrollable seizures, which are often the reason why many will die before their 4th birthday.

About The Schinzel-Giedion Syndrome Foundation

The Schinzel-Giedion Syndrome Foundation is a registered UK charity (Number 1186327), established in 2019 by an international group of parents of children with Schinzel-Giedion Syndrome (SGS). The charity is supported by a Scientific and Medical Advisory Board (SMAB), including researchers at renowned institutions, medical geneticists, paediatric clinicians and industry-level therapeutic developers. The Schinzel-Giedion Syndrome Foundation is the only SGS patient group and serves to represent the international SGS community. https://www.sgsfoundation.org

About The European Joint Programme on Rare Diseases (EJP RD)

The European Joint Programme on Rare Diseases (EJP RD) brings together over 130 institutions from 35 countries to create a comprehensive, sustainable ecosystem allowing a virtuous circle between research, care and medical innovation https://www.ejprarediseases.org/

Contact The Schinzel-Giedion Syndrome Foundation

Nuala Summerfield, Founder and Chair
Tel: +44 (0)7957 168815
nuala@sgsfoundation.org
https://www.sgsfoundation.org

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#schinzelgiedionsyndrome
#sgsfoundation
#raredisease
#rareepilespy

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Recurrence Risk

In this photo: Caroline

Recurrence Risk

This is a very important question for parents with a child diagnosed with Schinzel-Giedion Syndrome, considering having another child.

In this photo: Caroline

Recurrence Risk

This is a very important question for parents with a child diagnosed with Schinzel-Giedion Syndrome, considering having another child.

This information has been written for our website by Dr. Rocío Acuña Hidalgo, MD PhD Molecular Geneticist and Member of our Scientific and Medical Advisory Board

What is our risk of having another child with Schinzel-Giedion Syndrome? 

One of the most important questions for couples with a child diagnosed with Schinzel-Giedion Syndrome is to understand what is their risk of having another child with the same disease. This is known as “recurrence risk”. 

Parents who have a child with Schinzel-Giedion Syndrome are typically counselled that their recurrence risk is very low, with the risk of having another child with the same disorder at less than 1 in 100. 

Schinzel-Giedion Syndrome is always caused by new mutations in the SETBP1 gene 

Genetic tests for Schinzel-Giedion Syndrome (SGS) will usually find the disease-causing mutation in the blood or saliva of the child with SGS but not in the blood or saliva of the parents. This is because the genetic mutation that causes SGS is not in the cells of the parents’ body, but appears for the first time either in the father’s sperm cell or in the mother’s egg cell. During fertilization of an egg by a sperm cell, if either the sperm or the egg cell has the mutation that causes SGS, the baby will have the genetic mutation and will be born with SGS. 

Because the disease-causing mutation appeared for the first time in the father’s sperm cell or mother’s egg cell by chance, it is very unlikely that the mutation appears a second time by chance. This is why couples with a child who has SGS are counseled that the risk of recurrence is very low. Additionally, other members of the family (such as parents, siblings or other children of the couple with a child with SGS) do not have additional risk of having a child with SGS. 

Recurrence risk and mosaicism for the mutation that causes SGS 

In very rare cases, couples have been reported to have more than one child born with SGS. This can be a source of concern for parents who have a child with SGS and are thinking about having more children.  

Couples who have more than one child with SGS have germline or gonadal mosaicism for the mutation that causes SGS. Germline or gonadal mosaicism means that the genetic mutation that causes SGS appeared in more than one sperm cell in the father or more than one egg cell in the mother. Couples who have germline or gonadal mosaicism, have a higher risk of recurrence; the genetic mutation that causes SGS can still be found in one of the sperm or egg cells of the parents, which could lead to a second child being born with SGS. The risk of recurrence depends on the degree of germline mosaicism (i.e. how many sperm or egg cells there are with the genetic mutation). In even rarer cases, the genetic mutation can also be found in blood of the parents, even if the parent has no signs or symptoms of SGS. This is known as “gonosomal mosaicism” and recent research suggests that for these couples, the risk of recurrence is also higher. 

Please note: this example above uses the father for illustration purposes only, but it could equally be the mother who had a de novo mutation in a single egg cell, who has germline mosaicism or who has gonosomal mosaicism, resulting in a child with SGS.

Summary 

The recurrence risk for most couples with a child diagnosed with SGS is very low (<1%). Couples with a child diagnosed with SGS and who would wish to have more children but are concerned about their risk of recurrence should discuss their options with a genetic counselor (e.g. early prenatal diagnosis).  

On rare occasions, couples may have germline or gonosomal mosaicism for the mutation that causes SGS, which increases their recurrence risk. Unfortunately, currently there is no way to know whether a couple has germline mosaicism. However, couples can be tested for gonosomal mosaicism by trying to detect the disease-causing mutation in the blood of the parents. If the disease-causing mutation is found in the parents’ blood, the risk of recurrence is higher. 

Note: 

Detection of parental gonosomal mosaicism needs to be carried out with Next Generation Sequencing and not with Sanger Sequencing (please refer to Rahbari et al. Timing, rates and spectra of human germline mutation, Nature Genetics 48, 126–133(2016) 
URL: http://dx.doi.org/10.1038/ng.3469 or https://core.ac.uk/download/pdf/30665023.pdf).  

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