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!

 

#RareDiseaseDay #29BOSFacts

29days

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!

Bewaren

Year of AЯRE

We would like to share you the amazing journey of the AЯRE Foundation and highly recommend to subscribe their Newsletter. You can read the latest newsletter here:

2018 YEAR IN REVIEW

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:

Health tips and strategies
• Techniques to assist children with visual impairments
Food is your “medicine” in supporting healthy memory
Strategies for better sleep

Success story!
Amelia learns to walk.

Navigating rare disease
• Adaptive PE
• All about Augmentative and Alternative

Communication
• Cultivating a strong marriage
• Complex care – An administrative headache!

Learn all about music therapy.

Ask an expert
• Q&A with Dietician Dee Madore
• Gene therapy and editing Q&A with Dr. Loren D.M. Pena

2018 Inaugural ASXL Research Symposium was a huge success!

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.

Read here all about our journey: https://mailchi.mp/ee95de46997a/arre-newsletter-may-1709661

Thank you for being part of our AЯRE community. We wish you a joyous, festive and happy holiday season!

Cheers,
AЯRE Team

Happy Holidays

The magic of Christmas never ends and it’s greatest of gifts are family and friends.

Wishing you a season of gladness, a season of cheer,
and to the top of it all, a healthy and wonderful year!

Merry Christmas & Happy New Year!

Asxl1 loss effects lung maturation

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).

» Read here the article: Asxl1 exerts an antiproliferative effect on mouse lung maturation via epigenetic repression of the E2f1-Nmyc axis. By Seungtae Moon, et al. Cell Death & Diseasevolume 9, Article number: 1118 (2018). https://doi.org/10.1038/s41419-018-1171-z

BOS Meeting Point

Meeting Point

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!

Is this list incomplete? Please feel free to send us your Story about raising a child with Bohring-Opitz Syndrome. Thank you!

 

ASXL Conference – registration now open

2018-6-23 ASXL Research Symposium Agena

More information about the first Research Symposium about all ASXL Families you can find on the website of the AЯRE Foundation.

Register here: registration asxl

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

 

Pulmonary hypertension

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)

Maternal Mosaicism

Inheritance mosaicism2

This new article by Emma Bedoukian and collegues present the first report of germline inheritance of Bohring-Opitz Syndrome.
“[…] Most patients [affected with Bohring-Opitz Syndrome (BOS)] […] have a de novo nonsense or frameshift variant in ASXL1. We report a case of BOS caused by a pathogenic ASXL1 variant inherited from a germline mosaic mother. The ASXL1 mutation was detected via trio exome sequencing. The sequencing data demonstrated that the variant was inherited maternally but that the maternal variant was underrepresented in comparison to the normal allele. These results suggested maternal mosaicism for the variant. Additional testing on the mother was performed on buccal cell DNA, which was also consistent with mosaicism. The mother had been reported to be healthy and the family history is unremarkable. This is the first report of BOS caused by a mutation inherited from an unaffected, presumed germline mosaic parent. This phenomenon has been reported for other traditionally de novo dominant disorders like CHARGE syndrome and Cornelia de Lange syndrome. This case emphasizes the need for accurate low but non‐negative recurrence risk counseling for families with children with BOS and it impacts exome interpretation strategy.”

» Bedoukian E, Copenheaver D, Bale S, Deardorff M. Bohring‐Opitz syndrome caused by an ASXL1 mutation inherited from a germline mosaic mother. Am J Med Genet Part A. 2018;176A:1249–1252. https://doi.org/10.1002/ajmg.a.38686

Inheritance mosaicism1

In most of the cases Bohring-Opitz syndrome (BOS) is the result of a novo mutation in the  ASXL1 gene. The risk of having another child with Bohring-Opitz Syndrome is low. (Russell, B. et al. 2018)

Inheritance de novo

»Read also our blog post https://bohring-opitz.org/2017/10/30/bos-inherited-by-germline-mosaicism/

Research for ASXL Syndromes

fall back imageWe are thrilled to announce the launch of the ASXL Rare Research Endowment (AЯRE) Foundation (www.arrefoundation.org)! 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.

Our ASXL families — who have Bohring-Opitz Syndrome (ASXL1), Bainbridge-Ropers Syndrome (ASXL3), and Shashi-Pena Syndrome (ASXL2) – face extraordinary challenges and uncertainty. AЯRE will bring together the medical and scientific leaders to study ASXL genes and clinical challenges so that we can improve care management strategies, assist with patient advocacy, and ultimately introduce potential treatments/cure.

I would like to thank our incredible team of officers & board volunteers for all their efforts to make this possible! We are on this journey together and need your help to realize this vision. Please consider to rally family & friends to support this important cause through volunteer efforts and donations.

VOLUNTEER

DONATE

AЯRE has more exciting news and actionable information ahead. Check out our website (www.arrefoundation.org) to learn more about our plans, join us on Facebook, and sign up for our newsletters.

NEWSLETTER

Our ASXL children are an incredible inspiration and have changed our perspective on life. Let’s join together so that we can become stronger advocates and provide our children with the best lives possible.

I am excited about our road ahead and look forward to hearing from you!

Best,
Laura Badmaev
Chair, AЯRE Foundation
laura@arrefoundation.org