ASXL-related disorders

ASXL-related disorders are a group of rare neurodevelopmental conditions that include Bohring-Opitz Syndrome (ASXL1), Shashi-Pena Syndrome (ASXL2), and Bainbridge-Ropers Syndrome (ASXL3). These syndromes are caused by changes in the ASXL genes and are associated with complex medical, developmental, and behavioral needs.

ASXL-related disorders

ASXL-related disorders are a family of rare genetic disorders caused by changes in one of the three ASXL genes: ASXL1, ASXL2, and ASXL3. The genetic change, commonly called a variant or mutation, usually happens randomly around the time of conception (de novo). In rare cases, it may be inherited from a parent.

Variants in the ASXL genes disrupt the typical DNA sequence, which are the instructions the human body needs for typical development and functioning. Variants in the ASXL genes are known to impact the development and function of multiple body systems, including the brain and nervous system. Because of the impact to the brain, ASXL-related disorders are typically classified as neurodevelopmental disorders.

Symptoms

The three ASXL-related disorders have overlapping symptoms and features as well as features that are unique to each disorder. There is a wide spectrum of symptoms and severity that may evolve over time. We estimate that there are fewer than 1,000 people diagnosed with ASXL-related disorders in the world, with many people living undiagnosed who have not had genetic testing. There are currently no specific treatments to address the underlying cause of ASXL-related disorders. Treatment plans typically include a multidisciplinary team of specialists and therapists to address symptoms.

What ASXL genes do

The ASXL gene family (ASXL1, ASXL2, and ASXL3) helps control when and how other genes are turned on or off – a process known as epigenetics. These genes work together as part of a process called the polycomb deubquitinase (PR-DUB) complex, which helps open and close tightly wound sections of DNA (called chromatin) so cells can read the right set of instructions at the right time during development. Because changes in these genes affect how DNA is used without changing the DNA itself, ASXL-related disorders are considered epigenetic disorders. They are also categorized as chromatin modifying disorders, or chromatinopathies.

Why we support the three ASXL-related disorders together

The ARRE Foundation focuses on the three ASXL-related disorders because they are closely connected at a biological level, share similar underlying mechanisms, and have similar clinical features. By studying them together, researchers can learn more efficiently and apply discoveries from one disorder to the others, saving time and resources. This creates an “economy of scale” in research, making it more cost-effective to invest in shared tools, models, and data.

In addition, since each disorder affects a very small number of people, combining efforts across all three conditions helps build a stronger, more unified community. This “strength in numbers” makes it easier to attract researchers, funding, and attention to the needs of all families affected by ASXL-related disorders.

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ASXL-related disorders