Today is BOS day!

Gold and Denim for Bohring-Opitz Syndrome Awareness Day April 6th

Good morning dear BOS Family,

Today, April 6th is Bohring-Opitz Syndrome Awareness Day. This day was chosen because that’s the day that the Bohring-Opitz Syndrome support group was created on Facebook, on April 6th 2011! This group has helped so many families to connect all over the world!

With this awareness day we want to encourages people to learn more about Bohring-Opitz Syndrome to improve the lives of children and their families and caregivers living with this rare genetic condition.

Why this colors? Many children with Bohring-Opitz Syndrome are suffering from high myopia. Contrasting colors like blue and yellow are the best perceived colors. Bohring-Opitz Syndrome is a rare genetic condition. Less than 60 cases are reported in medical literature worldwide. These are official numbers but here in our support group the number is now estimated to be closer to 200 families. However, throughout new diagnoses and available and better genetic testing, the number of children diagnosed with BOS became significant higher, Bohring-Opitz Syndrome is still ultra-rare and underdiagnosed. So that’s why we chose blue denim as awareness color for rare and genetic diseases. The second color is gold because our children love shimmering objects. And above all, our children are worth their weight in gold. The diamond is to honor all our children who became wings too early.

We are excited to see so much engagement for us, the BOS Family.

The Bohring-Opitz Syndrome Foundation is still dedicated to raise awareness for Bohring-Opitz Syndrome. In their press release (http://bos-foundation.org/blog/2019/4/5/spreading-awareness-of-bohring-opitz-syndrome-ultra-rare-syndrome-celebrates-its-day-in-the-spotlight you can read how they continue to strive to improve the quality of life for families living with BOS.

BOS Awareness Day (source: BOS Foundation)

Today is also the day that the ASXL Rare Research Endowment (AЯRE ) Foundation celebrates her first Anniversary. Happy Birthday AЯRE!

The AЯRE Foundation was born to support research that will increase our understanding of the ASXL genes and to improve the treatment of individuals with congenital ASXL mutations. 

The leading cause for Bohring-Opitz is a mutation in the ASXL1 gene. ASXL1 belongs to human gene family with 3 members (ASXL1, ASXL2 – Shashi-Pena, and ASXL3 – Bainbridge-Ropers). There are many similarities between these three groups and they have much more in common than different.

ASXL Diagram by Caitlin Calder (source: http://www.arrefoundation.org)

AЯRE key tenets include good stewardship of our resources and transparency. For this day the AЯRE Foundation published her donor summary: https://www.arrefoundation.org/arre-donor-summary-2018.

Priorities of the AЯRE Foundation. Donor Summary 2018. (Source http://www.arrefoundation.org)

However we sometimes have the feeling that too little is known about the syndrome,  researchers are continue working on Bohring-Opitz syndrome. Did you know that in the past year that more than 10 new publications have been published about BOS?

We would like to highlight the work of Dr. Bianca Russell and Dr. Wen-Hann Tan, who have done amazing progress in the research history of Bohring Opitz Syndrome due creating the Bohring-Opitz Patient Registry. If you haven’t enrolled yet, please consider to participate to the patient registry. Only research is creating new knowledge!

On the last ASXL conference in Los Angeles Dr. Bianca Russell (The first year of the Bohring-Opitz Patient Registry ) and Dr. Wen-Hann Tan (ASXL1 Clinical Discussion) gave presentations about ASXL1/Bohring-Opitz. You can read and watch the presentations on the News Page of the AЯRE Foundation. The latest publication of Dr. Bianca Russell and Dr. Wen-Hann Tan  you can read here:  Bohring-Opitz Syndrome (https://www.ncbi.nlm.nih.gov/books/NBK481833/) If you are interested to learn more about Bohring-Opitz, you find more articles on our website.

We are optimistic for the future of the BOS Family and looking forward to see all your personal creations and how you mark this special day! Let’s bring together children living with BOS, their families and caregivers out of isolation and put them in the spotlight by wearing GOLD & BLUE DENIM on April 6th!

BOS Patient Registry 1st Year

Did you know that more than a half (55%) were not suspected to have Bohring-Opitz? Read and watch more interesting findings of the BOS Patient Registry by Dr. Bianca Russell en Dr. Wen-Hann Tan!

This presentation was given at the ASXL Symposium of the
AЯRE Foundation in Los Angeles. Watch also the livestream of the presentation on the website of the ARRE Foundation.

Part 1. Bianca Russell: “ASXL Related Disorders: The First Year of our Registry.”

Part 2. Bianca Russell: “ASXL Related Disorders: The First Year of our Registry.”

Dr. Bianca Russell received her bachelors degree from Connecticut College in New London, Connecticut in 2008 and her medical degree from the University of California, Irvine in 2013. She completed her residency in Paediatrics and Human Genetics at the Cincinnati Children’s Hospital in Cincinnati, Ohio and will be a Genetics attending at UCLA beginning in June of 2018. She has focused her career and research on clinical genetics with a particular interest in the management of genetic conditions including Bohring-Opitz Syndrome.

BOS Gen found in a boy and ExAC

Again the recent publication by Urreizti et al. shows that pathogenic gene variants are part in a reference database should be taken into account. In order to assess genetic variants, reference population databases such as the Exome Aggregation Consortium (ExAC) database are part of researches. It is assumed that in this population database pathogenic gene variants are absent or rare. Urreitzi et al. present a boy who has already been clinically diagnosed with Bohring-Opitz Syndrome (BOS). Sanger sequencing of ASXL1 revealed the p.Gly646Trpfs*12 mutation, an ASXL1 variant that is considered as causing Bohring-Opitz Syndrome. This variant is present in 132 persons from the reference database ExAC. Even though Carlston et al. 2017 discovered that in the ExAC database are BOS causing ASXL1 variants in individuals who are healthy with the conclusion that somatic mosaic of ASXL1 variants should be taken into account.


» Urreizti R, Gürsoy S, Castilla‐Vallmanya L, et al. The ASXL1 mutation p.Gly646Trpfs*12 found in a Turkish boy with Bohring‐Opitz Syndrome. Clin Case Rep. 2018;00:1–5. https://doi.org/10.1002/ccr3.1603

» Carlston CM, O’Donnell‐Luria AH, Underhill HR, et al. Pathogenic ASXL1 somatic variants in reference databases complicate germline variant interpretation for Bohring‐Opitz Syndrome. Human Mutation. 2017;38:517–523. https://doi.org/10.1002/humu.23203

 

Bohring-Opitz Syndrome

genereview

Bianca Russell, Wen-Hann Tan and John M Graham have published a new comprehensive overview about Bohring-Opitz Syndrome (BOS) in GeneReviews.

After the publication of the Unique leaflet by Joanna Kennedy (2017), the “Clinical management of patients with ASXL1 mutation and Bohring-Opitz Syndrome […]” by Bianca Russell and colleagues (2015) and previously published article about BOS (Magini, P. et al. 2012, Hoischen, A. et al. 2011 and Hasting,R. et al. 2011) this review is an excellent resource to understand and learn about Bohring-Opitz Syndrome. Part of the publication are summary, diagnosis, clinical characteristics, genetically related disorders and management of Bohring-Opitz Syndrome as well as genetic counselling and because it is written in understandable language it is an exceptional reference work not only for experts but for parents also!

Please read the full text of “Bohring-Opitz Syndrome” here: https://www.ncbi.nlm.nih.gov/books/NBK481833/

Germline mutation but no BOS

We have learned that  germline mutations of human ASXL1 is the cause of Bohring-Opitz  syndrome (BOS). Germline means its a novo ASXL1 mutation, the gene mutates at conception, creating a developmental disorder that leads to BOS. Patients with somatic ASXL1 mutation (the mutation formed during later life) have an increased risk of myelodysplasia (MDS), myeloproliferative neoplasms (MPN), and acute myeloid leukemia (AML) acute myeloid leukemia (AML), forms of blood cancer.

Karen Seiter and colleges present a father and son who have a identical mutation of ASXL1 with the inference that these cases support the diagnosis of a germline mutation of ASXL1. Interestingly this specific mutation has been reported in one case of Bohring-Opitz syndrome. Both, father and son have developed myelodysplasia to myeloid leukemia but have no Bohring-Opitz Syndrome.

» Read here the article of Karen Seiter and colleges: “Acute myeloid leukemia in a father and son with a germline mutation of ASXL1″ (Biomarker Research 20186:7, https://doi.org/10.1186/s40364-018-0121-3)

New cause for BOS?

Researchers have expanded the clinical spectrum of KLHL7 […] by describing a syndrome with features overlapping CS/CISS1 (Crisponi syndrome/cold-induced sweating syndrome type 1) and Bohring-Opitz Syndrome (BOS). At six patients with microcephaly, facial dysmorphism, including exophthalmos, nevus flammeus of the glabella and joint contractures with a suspected BOS posture in five out of six patients they found with whole-exome sequencing (WES) mutations in the KLHL7 gene.

Prior to 2011, geneticists relied on making a clinical diagnosis by recognizing the distinguishable physical characteristics in the appearance of their patients. In 2011, researchers at the Radboud University Nijmegen medical centre discovered one genetic cause of Bohring-Opitz Syndrome. They found that seven of 13 examined patients with the BOS phenotype had the novo mutation in the ASXL1 gene. However another six children with clinical diagnosis of BOS didn’t have this mutation, this indicates that other genes may be involved in this syndrome suggesting clinical and genetic heterogeneity, meaning there must be at least one other cause of BOS.

»Bruel A, Bigoni S, Kennedy J, et al: Expanding the clinical spectrum of recessive truncating mutations of KLHL7 to a Bohring-Opitz-like phenotype.

 

The BOS Registry

BOS registry 10

Our best chance to help individuals who are affected by Bohring-Opitz Syndrome (BOS) is a registry that will collect important information about raising a child with BOS and their medical history and build a resource for a better understanding of this rare disease for patients, caregivers as well for medical professionals.

The amount knowledge started small, with just four patients presented by Axel Bohring in 1999. Over the years, more and more cases were presented and our BOS Family is still growing.

The BOS & ASXL REGISTRY is here! We need your help in building such a resource and encourage you to become part of the “Bohring-Opitz Syndrome (BOS) & ASXL related Registry”. This registry, created by Dr. Bianca Russell and Dr. Wen-Hann Tan, is a milestone in the history of Bohring-Opitz Syndrome and the more people registered, the more valid and valuable the information becomes, which will result in a significant step in improving the lives of people affected with Bohring-Opitz Syndrome.

»Learn more about the registry!

Thank you for considering having your child or BOS-Angel join the registry. Your participation makes the difference!

 

Surveillance Recomendation

A new publication in the AACR (American Association for Cancer Research) by Jennifer M. Kalish and colleagues about uniform tumor screening recommendations for rare syndromes with increased risk for Wilms tumor, hepatoblastoma and other embryonal tumors like Bohring-Opitz Syndrome. “In the 43 cases reported by Russell and colleagues (2015), two patients developed WT and one had nephroblastomatosis leading to a renal neoplasm incidence of 7%. The small number of reported patients with BOS and high infant mortality rate indicates that the true cancer risk may be higher than reported.” (Kalish, 2017)

Abstract:

“A number of genetic syndromes [as is the case here among other syndromes, the Bohring Opitz Syndrome has been described] have been linked to increased risk for Wilms tumor (WT), hepatoblastoma (HB), and other embryonal tumors. Here, we outline these rare syndromes with at least a 1% risk to develop these tumors and recommend uniform tumor screening recommendations for North America. Specifically, for syndromes with increased risk for WT, we recommend renal ultrasounds every 3 months from birth (or the time of diagnosis) through the seventh birthday. For HB, we recommend screening with full abdominal ultrasound and alpha-fetoprotein serum measurements every 3 months from birth (or the time of diagnosis) through the fourth birthday. We recommend that when possible, these patients be evaluated and monitored by cancer predisposition specialists. At this time, these recommendations are not based on the differential risk between different genetic or epigenetic causes for each syndrome, which some European centers have implemented. This differentiated approach largely represents distinct practice environments between the United States and Europe, and these guidelines are designed to be a broad framework within which physicians and families can work together to implement specific screening. Further study is expected to lead to modifications of these recommendations.” (Surveillance Recommendations for Children with Overgrowth Syndromes and Predisposition to Wilms Tumors and Hepatoblastoma. Jennifer M. Kalish, Leslie Doros, Lee J. Helman, Raoul C. Hennekam, Roland P. Kuiper, Saskia M. Maas, Eamonn R. Maher, Kim E. Nichols, Sharon E. Plon, Christopher C. Porter, Surya Rednam, Kris Ann P. Schultz, Lisa J. States, Gail E. Tomlinson, Kristin Zelley and Todd E. Druley.

New Leaflet about BOS by Unique

Unique has published a new leaflet about Bohring-Opitz Syndrome (BOS)!

Written by Dr. Joanna Kennedy1 and reviewed by Professor Ruth Newbury – Ecob2 this information guide is an exceptional user guide designed to help families, caregivers, educators, and medical professionals, alike, understand and plan appropriate care for children with Bohring-Opitz Syndrome. Unique, winners of Eurodis Patient Organisation Award 2016, supports and informs anyone born with a rare chromosome disorder, their families and carers.

We are very grateful that also Bohring-Opitz Syndrome is included in the comprehensive offline database of family-friendly, medically-verified, disorder-specific information guides about rare chromosome disorders compiled by Unique and want to thank Dr. Joanna Kennedy and Dr. Ruth Newbury-Ecob for this outstanding publication.

»Read Unique (Understanding Chromosome Disorders) : Bohring-Opitz Syndrome. Leaflet by  Unique 2017.


1 Academic Paediatric Trainee, Severn Deanery

2 MB ChB, MD, FRCP, FRCPCH, Consultant Clinical Geneticist, Department of Clinical Genetics, University Hospitals Bristol NHS Foundation Trust

29 Facts about BOS

29days

On the occation of Rare Disease Day last year we published 29 #BOSFACTS. A year has past and these facts about Bohring-Opitz Syndrome are still up to date. The Rare Disease Day slogan is this year  ‘With research, possibilities are limitless’. Let’s go for it!

#BOSFACT 1   RARE

Bohring-Opitz Syndrome is RARE – fewer than 60 children are published in medical articles since 1999. The largest number of children live in USA and UK, in other countries there are just 1-3 children diagnosed with Bohring-Opitz Syndrome.

#BOSFACT 2   INTERNATIONAL

Bohring-Opitz Syndrome knows no borders. Children with BOS lives around the world in 28 countries and speak many languages.

#BOSFACT 3  NAME

Bohring-Opitz Syndrome owes its NAME to the geneticists Axel Bohring and John M. Opitz. The terms ‘Bohring’, ‘Bohring-Opitz’ and ‘C-like syndrome’ have all been used to describe this condition. Because Frank Oberklaid reported another case there is also the  name ‘Oberklaid-Danks-Syndrome’ for ‘Bohring-Opitz-Syndrome’.

#BOSFACT 4  PUBLICATIONS

Since 1969 there have been 27 PUBLICATIONS on Bohring-Opitz Syndrome. Two articles are milestones in the medical history of BOS: 2011 the discovery of one genetic cause by Alexander Hoischen and 2015 the article of Bianca Russell who first presented treatments.

#BOSFACT 5   GENETIC CAUSE

Prior to 2011, geneticists relied on making a clinical diagnosis by recognizing the distinguishable physical characteristics in the appearance of their patients. In 2011, researchers at the Radboud University Nijmegen medical center used “next generation sequencing” to find the novo mutation in the ASXL1 gene as one GENETIC CAUSE of Bohring-Opitz Syndrome.

#BOSFACT 6   HETEROGENEOUS

BOS is genetically HETEROGENEOUS, meaning there must be at least one other cause of BOS. Because other children with a clinical diagnosis of BOS didn’t have this mutation, this indicates that other genes may be involved in this syndrome or  that a somatic mosaicism should be considered as cause in patients with a typical phenotype and no detectable mutation.

#BOSFACT 7  TREATMENT

2015 Bianca Russell and colleagues published an article about Bohring-Opitz Syndrome. Beside the presenting of eight new patients, in this article TREATMENT options  were discussed for the first time and the authors suggests certain patients with Bohring–Opitz syndrome should be monitored for Wilms tumors.

#BOSFACT 8   RESEARCH

Researchers around the world are working hard for a better understanding of Bohring-Opitz Syndrome. Investigations like the ongoing sequencing campaign in Spain, RESEARCH on “mouse models” and a German study of the mechanism of ASXL1 gene in human stem cells brings us a step further that one day these knowledge will results in therapies for BOS children.

#BOSFACT 9  SUPPORT

This year our Support group on Facebook is 5 years old. The group was started on April 6th 2011 just with a few families. Now there are almost 100 families of children with BOS united. This group offers so much SUPPORT and all the parents and caregivers there are amazing by helping each other. They all make these group so successful.

#BOSFACT 10   ANGELS

BOS children are ANGELS. Many children have passed away far too early. Bohring-Opitz Syndrome is a life limiting genetic condition with a high infant mortality.

#BOSFACT 11    HOPE

There is HOPE – Bohring-Opitz Syndrome is not as severe in all cases than originally foreseen, children could even reach adulthood. When the novo mutation on the ASXL1 gene were discovered, many children have finally gotten the diagnosis at a later age by WES (Whole Exome Sequencing).

#BOSFACT 12   ENGAGED

Parents around the world are pretty much ENGAGED by sharing their experiences in raising a child with Bohring-Opitz Syndrome. There are stories about partnering with doctors, finding helpful resources, and seeking answers… but mostly there are stories of persistence and strength and hope.

#BOSFACT 13   HAPPINESS

Children with Bohring-Opitz syndrome loves to play with shiny and sparkling objects. They love music and can’t get enough cuddles.

#BOSFACT 14   EMOTION

BOS kids feel like us: they have the same EMOTIONS. They are frightened, feel anger and pain. They have joy and happiness.

#BOSFACT 15   STRONG

BOS kids are vulnerable but also incredibly STRONG and brave.

#BOSFACT 16   DEVELOPMENT

Many children are diagnosed with ACC (Agenesis of the Corpus Callosum), a congenital (lifelong) brain abnormality. Common characteristics associated with ACC like vision and hearing impairments, low muscle tone, feeding and sleep difficulties, seizures, to name but a few, affect the DEVELOPMENT in different. But children with Bohring-Opitz Syndrome develop, they learn at their own pace.

#BOSFACT 17   INDIVIDUAL

Although children with Bohring-Opitz Syndrome looks very alike at birth, they are all INDIVIDUALS. Every child is unique and there are different levels and degrees of symptoms. Knowing one child with BOS, does not mean that all BOS children are the same. They are all individuals, regardless whether they have the same mutation on the ASXL1 gene.

#BOSFACT 18   BEAUTIFUL

Children with Bohring-Opitz Syndrome are BEAUTIFUL!

#BOSFACT 19   RESPECT

The word “retarded” is offensive, it hurts. Children with Bohring-Opitz syndrome deserve RESPECT.

#BOSFACT 20   WILLING

There was a time when parents were encouraged to send their BOS babies to mental institutions. What you see now is the hard work and determination of parents WILLING to fight the battle for their children, and for the many that have followed.

#BOSFACT 21   MEANING

Bohring-Opitz Syndrome is much more than just a medical diagnosis, a child with or without BOS has a MEANING, they are valuable!

#BOSFACT 22   DOCUMENTARY

The premiere of the DOCUMENTARY Kuluut will be coming soon. Kuluut is a documentary about Coen and his family. Coen is 4 years old and has Bohring-Opitz Syndrome. This film is about happiness and strength!

#BOSFACT 23   FOUNDATION

Established in 2015 by Carrie Hunsucker and Taylor Gurganus, the Bohring-Opitz Syndrome Foundation, Inc.- a 501c3 non-profit organization- is dedicated to improving the lives of people affected by BOS through the establishment of a medical advisory board, awareness Initiatives, and parent/patient advocacy.

#BOSFACT 24   EQUAL

The number of boys vs girls having Bohring-Opitz Syndrome is EQUAL. According to our knowledge there is no indication that Bohring-Opitz Syndrome is related to gender.

#BOSFACT 25   CHALLENGING

The list of ailments and physical characteristics associated with Bohring-Opitz Syndrome is long but some main health problems like feeding difficulties and respiratory issues are common.   The fact that still little is known and every child is unique makes it CHALLENGING to adapt the best treatment the child.

#BOSFACT 26   CURE

Currently, there is no CURE for Bohring-Opitz Syndrome. However, treatments may improve various symptoms and prevent complications.

#BOSFACT 27   INVOLVED

Families of children with Bohring-Opitz Syndrome are not alone. The engagement of family, friends, caregivers and medical professionals is huge! Doctors and nurses worldwide are working hard to work with us for solutions and to make life with Bohring-Opitz Syndrome better.

#BOSFACT 28   EXPERT

Parents know their child best – they become an EXPERT of their child. Together with professionals they strive to make living with Bohring-Opitz Syndrome optimal.

#BOSFACT 29   LOVE

BOS children teach us the true meaning of unconditional LOVE!

Bewaren