Bainbridge-Ropers Syndrome (ASXL3)

Gene sequencing, a type of broad genetic testing, is typically used to identify a change or variant in the ASXL3 gene. Bainbridge-Ropers Syndrome is a specific diagnosis usually linked to a particular type of genetic variant in the ASXL3 gene that causes a vague but recognizable set of clinical features. The specific genetic variants currently associated with Bainbridge-Ropers Syndrome are typically (but not always):

• De novo, meaning they are a new variant or mutation and is not inherited from a parent
• Pathogenic or likely pathogenic, meaning they are known or suspected to cause disease based on evidence analyzed by the testing laboratory
• Truncating variants, like a nonsense or frameshift mutation, that results in the production of a shortened protein than is produced by a typical gene
• Occuring in the last two sections (exons) of the ASXL3 gene

There are other types of ASXL3 variants, including inherited or missense variants. Some of the more comprehensive recent research papers do describe people with other types of ASXL3 variants and may use the term “ASXL3-related disorder” to describe this wider category of ASXL3-linked conditions. We’re still learning how these other variants affect people and how their symptoms may differ. See below for information about uncertain diagnoses, including a variant of uncertain significance (VUS).

Unless otherwise noted, the information on this page primarily uses the term Bainbridge-Ropers Syndrome, since most clinical research so far has involved people with this specific diagnosis. If your loved one has a different ASXL variant, you may still find this information and the community resources helpful. The ARRE Foundation is here to support everyone affected by changes in any of the ASXL genes, as we continue to learn more about these rare and complex conditions.

Uncertain diagnoses: If your loved one has a variant of uncertain significance (VUS) or otherwise does not have a definitive Bainbridge-Ropers Syndrome diagnosis, please reference our Uncertain Genetic Diagnosis resources for more information.

There is significant variability in the symptoms and clinical features in Bainbridge-Ropers Syndrome, including a wide spectrum of severity. We don’t yet know why changes in the ASXL3 gene cause this wide spectrum of symptoms and features (known as genotype-phenotype correlation).

Some of the most common characteristics of Bainbridge-Ropers Syndrome include:

• Gross motor delay of varying severity
• Intellectual disability of varying severity
• Delayed or absent speech, including having no or limited spoken words
• Characteristic but non-specific facial features
• Dental and oral abnormalities, including high arched palate and crowded teeth
• Low muscle tone (hypotonia)
• Feeding difficulties particularly in infancy, including cyclic vomiting or reflux that may be extreme and lead to hospitalization
• Constipation and motility issues
• Respiratory infections, particularly in infancy
• Behavioral concerns, including aggression, screaming, and general emotional dysregulation
• Autism or autistic traits, including sensory processing challenges, stereotypies (hand flapping, rocking), and inflexibility with changes in routine
• Orthopedic concerns, including scoliosis and kyphosis
• Seizures
• Sleep disturbances, including irregular sleep/wake cycles
• Obstructive and/or central sleep apnea

This list includes features documented in the medical literature and symptoms observed in the ASXL3 family community.

As genetic testing becomes more widely accessible, we are learning of more people who have been living undiagnosed with Bainbridge-Ropers Syndrome. The oldest known individuals with Bainbridge-Ropers Syndrome are in their thirties.

We don’t know much yet about what life looks like past childhood and young adulthood for someone with Bainbridge-Ropers Syndrome. Some symptoms seem to change over time, including some that improve (such as feeding difficulties) and some that worsen (such as orthopedic challenges and challenging behaviors). From the family community, we know that individuals with Bainbridge-Ropers Syndrome have a wide range of skills and abilities that will influence their ability to live independently. Most of the individuals we are aware of with Bainbridge-Ropers Syndrome cannot live independently and will require some degree of lifelong care.

Bainbridge-Ropers Syndrome is not known to be a life-limiting disorder and it is not known to be a neurologically degenerative disorder where cognitive function and ability decreases over time. You can help us learn what life with Bainbridge-Ropers Syndrome looks like over time by enrolling your loved one in the ASXL-Related Disorders Natural History Study.