German living in The Netherlands together with my husband and mother of four, writing about the rare disease Bohring-Opitz Syndrome (BOS) of my first born son at bohring-opitz.org and founder of the BOS support group on Facebook.
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 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.
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!
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!
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!
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.
On the occasion of Rare Disease Day we published 29 #BOSFACTS two years ago. Annother year has past and these facts about Bohring-Opitz Syndrome are still up to date. But there are important news for the Bohring-Opitz Family:
Research on Bohring-Opitz Syndrome are still going on and more medical articles about Bohring-Opitz Syndrome are published. The BOS & ASXL REGISTRY is here! More and more BOS Families enrol the BOS Patient Registry and help in building up 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 will result in a significant step in improving the lives of people affected with Bohring-Opitz Syndrome.
Last year the ASXL Rare Research Endowment (AЯRE) Foundation (www.arrefoundation.org) is launced! AЯRE will provide sustainable support for evidence-based research that will increase our understanding of the ASXL genes and improve the treatment of individuals with congenital ASXL mutations. This year this foundation will organize the second ASXL Conference for researchers and families.
And last but not least the Hollywood award winning documentary KULUUT can now be seen worldwide.
#BOSFACT 1 RARE
Bohring-Opitz Syndrome is RARE – less than 100 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. Update: 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.
#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.
Update: This year we will celebrate our 8th birthday!
#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!
Update: The award winning documentary KULUUT is a great success and is now seen worldwide also with English subtitles!
#BOSFACT 23 FOUNDATION
Established in 2015 by Carrie Hunsucker and Taylor Gurganus, the Bohring-Opitz Syndrome Foundation, facilitate birthday/sympathy gifts to individuals with Bohring-Opitz Syndrome who have joined their Birthday club. The Foundation also sends welcome baskets to patients who are newly diagnosed with Bohring-Opitz Syndrome. Furthermore, the foundation organizes an annual meet up event in the United States.
Update: This year the AЯRE Foundation will have her 1st Anniversary. The AЯRE Foundation is the first foundation who supports and finances research on Bohring-Opitz, Shashi-Pena and Bainbridge-Ropers Syndrome, all on ASXL Family!
#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!
We would like to share you the amazing journey of the AЯRE Foundation.
ASXL Rare Research Endowment (AЯRE) Foundation was launched in April to
support research that will increase our understanding of the ASXL genes
and to improve the treatment of individuals with congenital ASXL
mutations, and it has been quite a year! These are some of our favorite
moments:
2019 calendars still available! Give the gift of support for children with all types of ASXL syndromes. From December 1, 2018 through January 31, 2019, anyone who donates $30USD or more to AЯRE will receive a beautiful 2019 AЯRE Foundation Calendar.
Thank you for being part of our AЯRE community. We wish you a joyous, festive and happy holiday season!
Fig. 8: Hypothetical model for the epigenetic role of Asxl1 in regulating Nmyc expression during mouse fetal lung development. From: Asxl1 exerts an antiproliferative effect on mouse lung maturation via epigenetic repression of the E2f1-Nmyc axis. DOI 10.1038/s41419-018-1171-z
An important step towards a better understanding of the mechanism of ASXL1 mutation and Bohring-Opitz syndrome!
Little is known about the role of an ASXL1 mutation in the organ development. “Recent studies using Asxl1-null mouse models indicated a critical role for Asxl1 in development. Depending on the model, Asxl1 loss causes embryonic lethality and developmental abnormalities, including dwarfism, anophthalmia, microcephaly, kidney podocyte defects, and craniofacial defects.” In this study, published in ‘Cell Death and Disease’, Moon et. al. discovered that ASXL1 gene affect the lung development. They noticed that Asxl1−/− mouses were dying just after birth due to cyanosis, a respirator failure and suspected a reduced air space and a defective lung maturation. This prompted the researchers to investigate the underlying mechanism, focusing on the role of Asxl1 in lung development. Comparing a normal wild mouse, the Asxl1−/− mouse lung sank and […] failed to inflate with air because of its thicker alveolar wall, smaller air space, and more numerous small alveoli.
In most of the patients with Bohring-Opitz Syndrome the novo mutation in ASXL1 has been identified. Respiratory infections and reactive airway disease are common in patients with BOS and leading cause of death in the first two years of live (Russell et.al. 2016).
Having support and community resources can help increase your confidence in managing Bohring-Opitz-Syndrome (BOS), enhance quality of life, and assist in meeting the needs of other family members. Parenting is often challenging, and parenting a child with a chronic condition like BOS can add additional stress to the day-to-day challenges. It’s important to remember you’re not alone in your situation. There are people who have experience in supporting and caring for children with Bohring-Opitz Syndrome. They can provide information about all aspects of living with Bohring-Opitz Syndrome.
If you are the parent or caregiver of a child with BOS, it might be helpful to talk with other parents who have a child with the same condition in our “Bohring-Opitz Support Group”.
A child with Bohring-Opitz Syndrome will have a life that is different from than most children, but Bohring-Opitz children have delightful personalities and are extremely lovable. They will give you love that is totally unconditional.
Please feel free to meet these amazing families who have created their own personal Facebook Pages about raising a BOS child and see how they enjoy their wonderful children!
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
A new case report at Kagoshima City Hospital, Kagoshima, Japan describes in a newborn with Bohring-Opitz Syndrome Pulmonary Hypertension (PH). Children with Pulmonary (= lungs) hypertension (= high blood pressure) have small passageways, blood vessels, in the lungs and because these passageways are so narrow, there is a very high blood pressure in the pulmonary blood vessels. The heart therefore has to work much harder than normal so that the body gets enough oxygen. Children with PH may occasionally suffer from shortness of breath.
Despite treatment, the infant died from the consequences of severe heart failure.
» Read here the article “Lethal persistent pulmonary hypertension of the newborn in Bohring–Opitz syndrome” by Masaya Kibe et al. (https://doi.org/10.1002/ajmg.a.38681)
