ASXL3 Mutations &
About ASXL3 Mutations and Bainbridge-Ropers Syndrome
What is an ASXL3 mutation?
ASXL3 is one of approximately 20,000-25,000 genes that make up the human genome. The ASXL3 gene is located on chromosome 18. *DNA is like a library that has instruction books for your body. Each book contains instructions for your body to perform a particular function. The type of mutation that is found in people with ASXL3/BRS is a truncating mutation. Truncating means that the the mutation is sending out a "stop" signal where there shouldn't be one. It's as if a reader in the library encounters a message that tells them to stop, and they cannot read any further. The instructions in the book are incomplete and the gene can not properly carry out its function.
*I am not a geneticist or a doctor. In fact, science is not my strong suit. This is simply my own way of understanding the complexities of the human genome. If you want basic and comprehensive information on genetics, the National Institute of Health has an excellent site called
What is Bainbridge-Ropers Syndrome?
Bainbridge-Ropers Syndrome (BRS) is named after the genetic researchers who discovered the location of ASXL3 gene and documented some of the ways it affects people with the mutation. BRS is a list of common traits and symptoms that some people have when their ASXL3 gene has a mutation. A few of these symptoms include developmental delays, repetitive behaviors (like head shaking), feeding difficulties, low muscle tone, apraxia of speech, vision problems, and low-set ears.
How did this happen?
No one knows exactly how or why the ASXL3 mutations occur. It is important for parents to understand that their child's condition is in no way their fault. Nothing they did caused the mutation to happen and there was nothing they could have done to prevent it from occurring. For parents who have had their genes sequenced, neither of them carried the ASXL3 mutation. Researchers believe the mutation was random and spontaneous and that it probably occurred within a few hours of conception. The ASXL3 mutation is classified as a de novo truncating mutation. De novo means the mutation was spontaneous and truncating mutation means there is a stop signal in the gene where there shouldn't be one.
What are the key features of ASXL3/BRS?
Most of the children: are nonverbal, have intellectual disabilities, developmental delays, hypotonia (low muscle tone), exhibit stereotypic (repetitive) behaviors such as hand flapping and head shaking, poor eye contact, sleep issues (difficulty falling asleep, sleep apnea), inappropriate/compulsive laughter, fascination with water, eating difficulties, autism or autistic-like traits, mobility issues, sensory sensitivities, short attention span, short nose with anteverted nares (nostrils end lower than the tip of the nose), a high forehead, and low set ears.
Some of the children have: acid reflux (some have had Nissen fundoplication surgery), a clinical diagnosis of autism, a high arched palate, self harming behaviors, bruxism (grinding teeth), g-tubes, high pain tolerance, deep palm creases, collapsed arches, strabismus (eyes sometimes point in different directions), constipation, frequent ear infections (PE tube placement), failure to thrive at birth, microcephaly, lower than average weight/height, vision problems, adenoids/tonsils removed, precocious (early onset) puberty, and dysphagia (swallowing disorder).
A few of the children: have seizures, rarely produce tears, tracheostomy.
What does this mean for my child?
This is probably the most complex question that parents ask. The truth is that every child is different. There is a spectrum, which means a child with an ASXL3 mutation may be severely affected while another child is more mildly affected. Most children fall somewhere between those two extremes.
Is there a cure?
There is currently no cure for an ASXL3 mutation. But that does not mean there will never be a cure and the science of genetics has progressed faster than anyone thought possible. There are several institutions looking for ways to help children with BRS. Please look under our research section to see what research is currently being conducted. We will never give up searching.
What are the chances of having another child with ASXL3/BRS?
The chances of having a second child with ASXL3/BRS is extremely unlikely. Geneticists have put the chances of having a second child with BRS is approximately 1%. Your chances of getting struck by lightning are higher than having a second child with ASXL3/BRS.
How can I best help my child?
Almost every child diagnosed with ASXL3/BRS shows progress with intervention. Early intervention is critical and evaluations for speech, physical, and occupational therapy should be done as soon as developmental delays are evident. For many of the children progress can be slow but many have made significant gains in almost all areas of development.