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Schinzel-Giedion Syndrome Foundation

Schinzel-Giedion Syndrome Foundation

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

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Carla’s Story

Carla’s Story

July 2021

It’s a girl! I was overjoyed when the doctor told me. We had two boys, 2 and 4 years old at that time, we so much wished to have a girl. That was in the 17th week of pregnancy. Everything seemed to be perfect, we had two healthy children, what could happen. We waived additional preventive medical checkups.

There were no abnormalities whatsoever- until the 30th week of pregnancy. During the next ultrasound, the doctor was unusually silent. I had a bad feeling and suddenly he said something was wrong. “Look at the kidneys, both very large, congested and cystic.” I also had far too much amniotic fluid. I felt sick. My gynecologist was always very honest and direct when I asked him what this could mean. A syndrome. Trisomy 18 maybe. He told me to go straight to the hospital for an amniocentesis. The doctor at the hospital was more optimistic. It does not have to be that bad, just wait. The results of the test took 10 days. I think those were the worst days of my life, knowing our daughter was going to be sick or even might not be able to survive.

The result was unremarkable. It took a load off my mind; the doctor was stumped. He was still sure she had a syndrome, but I wanted to finish the pregnancy more positively and hoped that everything would be ok. He sent me to another doctor, in hospital, a nephrologist who was supposed to have better equipment. I went there every week for an ultrasound.

Unfortunately, he also found abnormalities in the baby’s brain. “That doesn’t mean anything, but in the worst case she could be blind.” I was totally insecure. We would have to wait until she was born, we should not worry so much. Easy to say… I was especially scared this time before the birth. I thought maybe she would not make it because she was sick. There was talk of possible adjustment problems and we thought about a C-section. But the doctors advised against it, the adjustment problems could be even harder for her, she was estimated at 4 kg, she would make it. So, we waited.

6 days past the calculated date of birth, on 11.05.2018 was the day. We were in the hospital for a routine check when it started. After 7 hours of being in labour she was delivered with the help of a suction cup. The birth was extremely dramatic, her heartbeat was gone, and everything had to be done very quickly. I felt as if she was ripped out of my body. The room was full of people, doctors, nurses and midwives. They tried to help her, she did not make any noise and did not breathe. I shouted, “What’s happening to her?” After a while, a doctor said she was breathing and now she was going to the NICU for monitoring. “What shall be her name?” – ” Carla”, I said. They would not let me see her. Meanwhile the doctors took care of me, I had atony and lost a lot of blood.

2 hours later my husband was allowed to visit Carla, I asked him to take a picture. She was cute, our baby, but I also noticed that she looked somehow different. I was extremely tired and so glad that she survived the birth.

The next day they brought me to her in a wheelchair. I could hardly see anything of her little face. A cap with a breathing mask covered it. She also had a feeding tube for the milk. I was allowed to take her in my arms and fell in love immediately. She had her tiny hands clenched in fists. Her little toes were slightly above the other toes and her ears looked a little deep out of her cap. “All very obtrusive, she even has a special voice” the doctors said. A team of geneticists would look at her in the next few days. I could not breastfeed her and so I went every day and tried to bottle-feed her my milk, it was very difficult. She always had too little oxygen and had to be supported.

Carla’s brothers could see her after 3 days. They had so many questions, I hoped I would soon have an answer. After one week I was able to go home. Carla had to stay for another week, then she was stable that she was transferred to the children’s hospital.

When the boys were in kindergarten, I was at the hospital with Carla helping her to practice drinking. Carla learned fast but she still had to use the feeding tube for milk. She had some tests that confirmed what we knew. Bilateral hydronephrosis and underdeveloped corpus callosum. Her eyes and ears could not yet be examined properly. Each kidney had 50% function, and her blood levels were good. So, if she learned to drink, she may go home. Thanks to the help of the nurses, we managed to achieve this. She was finally able to go home after a total of 5 weeks.

After 3 weeks was the first suspicion of Schinzel-Giedion Syndrome. Even the doctors had not heard of it yet. They would test for it. We did not want too much information about this syndrome until the final tests were done. We wanted to wait and see if it was confirmed or not.

The day I picked her up, I was full of joy. Finally, I can take our baby home. The doctor asked if I was alone, or if I needed to be picked up. I was alone, my husband worked all day and could not come. She wanted to talk to me before I went home with Carla.

She had good news and bad news. The good news is we have a confirmed diagnosis of Schinzel-Giedion Syndrome. And they got it quickly, which is not easy, because it is an exceedingly rare disease. But it would have been worse not to have a diagnosis, not to know what is wrong with her. The bad news was the consequences of this diagnosis. She would not tell us earlier. The child has a life expectancy of about 2 years, will develop very slowly, sometimes hardly at all. I was shocked. I wondered: “What could be worse than this prognosis?” I was devastated, phoned my husband immediately and told him everything. I waited with Carla for a while until I calmed down and went home with her.

I did not want to believe it. This day, which was supposed to be so happy, turned into a sad day. I bathed Carla and while I was massaging her, I talked to my friends on the phone. “I love my daughter, we will enjoy the baby time, as normally as we possibly can.” I did not want to learn more about this syndrome for a while…

It was a nice first summer with her. Carla was physically very well at that time. We wanted to make the time she had as beautiful as possible. I avoided any idea that she might not be with us for long and started to have faith in her. She was so cheerful, always sweet, cried little and slept well at night. The sucking on the bottle got better and better and I was able to calm her down most of the time by cuddling and holding her hands.

We celebrated Carla’s christening that very summer, we were afraid that her condition might decline. Before we took her with us on our summer holiday, we had to have some tests done. Will she be able to come with us? After a short time, we no longer needed the feeding tube. It was tedious and took a long time, but Carla managed her daily milk rations. The nephrologist was also satisfied: – Nothing has changed. Carla’s blood values are fine, the kidneys are working well. She hardly needs any support, no oxygen, hardly any medication, just antibiotic prophylaxis.

The holiday was great, we were in the mountains and I was able to take Carla with her 4 kg everywhere. Our family and friends accept and integrate her as she is. A wonderful experience, everyone had her on their arms and was interested in her, that gave me incredible strength. At the end of the holiday she would start to regurgitate a lot, the milk came out of her nose. I was worried, but her condition improved again, and it only came in transients. She choked more often, but we learned to deal with it well.

Soon we noticed that she was having seizures, more and more often. Her sleep got worse and she became very restless in the evening. After an EEG, she was given medication for epilepsy. She had more and more mucus and had to inhale more often to cough up the mucus. She often had a rhinitis and could hardly breathe. I became more and more worried: – Does she need a feeding tube after all?

Up to then we had always refused to accept this. I am always so happy when she drinks, one can really see how she likes it. I started to learn about Schinzel-Giedion Syndrome. I wanted to help her as much as I could and felt very alone. Nobody really knew about it. It became more and more obvious over time that she was not really developing well. We suspected that she could not see at all or only poorly, she hardly reacts to sounds. She does not reach for things and is rather apathetic. She does not cry and she does not laugh.

I searched the internet and found a story about a girl, with beautiful pictures. I read it, I think, three times. It was the first time I saw pictures of a child with this syndrome, and they all look so similar. It was a story written by the family, not by doctors. Experiences and feelings of people who are going through it themselves, like we are. It helped me so much. I was impressed by the love and strength of this mother. I wanted to be strong too. I also wanted to be there for Carla. What good is it for my baby if I cry, if I surrender or if I am sad. I want her to feel that I love her and will always be here for her.

Shortly afterwards we had an appointment with a geneticist. We were to be tested and Carla was examined. The doctors were very interested in her and had never seen a child with this syndrome before. We did not really get answers to our questions, just statistics and tables were shown to us. We were given forecasts about her short life expectancy, her poor mental and physical development. As expected, our genetic test was without result. Carla’s genetic defect is a new mutation. The geneticist pointed out to us that there was a Facebook group. I was very curious and willing to meet more parents. I received a very warm welcome and was overwhelmed by the many testimonials and pictures. A great community and support, for which I am still infinitely grateful.

The list of drugs has become long now, and it has not always been easy to administer everything to her orally. She is given medication for constipation, for flatulence, two drugs for epilepsy – which we have better, but not completely under control yet – and a sleeping pill and sedative. Along with the increased number of seizures, her sleep was so disturbed that she could not sleep for weeks and cried hysterically at night. That was a hard time for us. My husband works during daytime. While the boys are in kindergarten and school, I often have appointments with Carla, or we spend time at home or with friends. My parents moved to live with us, my mother supports me a lot and now we also have a home help, which is partly financed. So, we get along well.

Carla is developing very slowly, but we do as much as possible to support her. We go to physiotherapy once a week, Carla likes that very much. She likes to be moved and loves to be massaged. Once a week she has early vision support, we play a lot with lights and sounds, to try out what she likes. Carla makes very little progress, but she usually seems relaxed, opens her hands, can turn her head and lift it slightly. If leaned back against support, she can sit for a short time. She cannot see well, but she follows bright and colorful lights with her eyes. She also has hearing aids, but unfortunately, she still does not respond well to sounds. That is why we focus on the sensory aspect. Cuddling, caressing, putting lotion on and bathing, she loves that. Sometimes she smiles for a short time. I know Carla well, she does not have much expression on her face, but I can see exactly when she feels good, has pain or is angry.

We try to avoid unnecessary procedures and tests; we do not want her to be tormented just to get another diagnosis that can’t be changed. We do whatever is necessary so that she can live without pain. Of course, we undertake all preventive and routine examinations. We have met such great people, great doctors and nurses who have impressed me very much and to whom we also like to come.

Carla is now 2 years old. She is almost blind and almost deaf; she will not be able to sit or walk. She will not speak. Sometimes I am sad when I see children her age playing and romping, I wish the same for her. But we have accepted that Carla’s world is different. It does not matter what she cannot do, it’s important that she is doing well and that she can enjoy the life she has. And she can do that, everyone loves her, our family, our friends and acquaintances, everyone accepts and integrates her. Everyone is very understanding and respectful towards her and towards us. I am incredibly grateful and proud that we have such a great family and friends who do not turn away but stand by us and are there for us. We love you; we thank you!

“Life’s a bed of roses”, that was my slogan in life. To regard everything as positive as possible. With Carla I had to learn painfully that life is not always bedded on roses. But I would like it to be – and so we now live together with Carla in our rose garden. And it is good the way it is. It was not easy to write about Carla, such feelings can hardly be put into words. I hope that Carla’s story will be going on for a long time to come.

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Nuala’s Story

Read about Nuala and Ophelia at Rare Disease UK

Nuala’s Story

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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 rare cancer research.

Nuala Summerfield, Founder of The Schinzel-Giedion Syndrome Foundation with her daughter Ophelia

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.

Medically refractory 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

Contact Dr Alessandro Sessa, PhD

Division of Neuroscience Stem Cells & Neurogenesis Unit
San Raffaele Scientific Institute
via Olgettina 58
20132 Milan, Italy
Lab ph. +39 02 26434612
Office ph. +39 02 26435790
Fax: +39 02 26436585
Email: sessa.alessandro@hsr.it or ale.sessa81@tin.it

Contact Dr Carl Ernst, PhD

Douglas Research Centre
Department of Psychiatry, McGill University
6875 Boulevard LaSalle
Montréal, QC
H4H 1R3
Ph: (514) 761-6131 x3382
Fax: (514) 762-3023
Email: carl.ernst@mcgill.ca

Hashtags to use if sharing this article:

#schinzelgiedionsyndrome
#sgsfoundation
#raredisease
#rareepilepsy

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Happy 1st Birthday to SGS Foundation!

Happy 1st Birthday to The Schinzel-Giedion Syndrome Foundation!

Read the Story Here

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International SGS Awareness Day

International Schinzel-Giedion Syndrome Awareness Day 13 November 2020

By Emma Hudson, Secretary and Trustee of The Schinzel-Giedion Syndrome Foundation and mum to 2-year-old Jude who has SGS

Happy Birthday to Us!

13 November 2020 marked one year since the The Schinzel-Giedion Syndrome Foundation was registered as an official charitable organisation with the Charity Commission in the United Kingdom. Our Foundation was created to represent children living with SGS and their families all over the world. One of our missions is to raise awareness of SGS as a rare disease. This mission led us to establish the very first International SGS Awareness Day. What better way to celebrate our Foundation’s birthday?!

13 Days of Awareness

From November 1st, every day for 13 days in the run-up to our Awareness Day, we shared social media posts on Facebook, Instagram and Twitter featuring stories of children with SGS, important information about the condition and photographs of our SGS children and their families. The aim was for these posts to be shared far and wide so the world could learn about SGS and the way it affects our children’s quality of life. The international SGS community took the Awareness Day campaign to heart and shared our posts with not just family and friends but also medical professionals, researchers and other patient organisations.

Purple and Proud

We asked our families to share photographs of their children wearing purple to show their support for the SGS Awareness Day. There was a selection of heart-warming photos shared widely on Facebook and Instagram with the #sgsawarenessday and #schinzelgiedionsyndrome. The purple theme was strong throughout, with our children’s classmates and teachers wearing purple in support of SGS, as well as purple-themed painting and sensory play sessions and delicious purple SGS cakes!

SGS Photobombs Explode!

A very special part of the SGS Awareness Day was the creation of the eye-catching digital photo frames which featured children from all over the world who are part of our international SGS community. The photo frames were designed to be posted and shared on Facebook and Instagram by our families. The highlight was a beautiful short film created from all of the framed photos, which can be viewed here. A special thank you to Franco Grech, graphic designer, who created these digital frames and film as part of the pro-bono work he does for the Foundation. They really made an enormous impact and helped to make our Awareness Day so memorable.

Fundraising Success!

Another of our missions is to facilitate and support medical research that will help us find better treatments to improve the quality and length of life of children living with SGS. To do this we need to raise funds to support vital medical research.

A very important part of the SGS Awareness Day campaign was the fundraising that occurred within the SGS community. The call to arms was heard by our community and generous donations were received from across the globe.

This is a huge achievement for our very first fundraising campaign and we would like to thank everyone for their amazing generosity. We will soon share further information about the research projects that these funds will be supporting and the impact this research will have for our children.

Date for your diary: International SGS Awareness Day 2021 will be on Saturday 13 November 2021.

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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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