Xia-Gibbs Syndrome was one of the first disorders discovered using new whole exome sequencing (WES) technologies developed at Baylor College of Medicine Human Genome Sequencing Center in Houston, Texas. The research team, headed by Professor Richard Gibbs, discovered that Xia-Gibbs Syndrome arises from mutations in the AHDC1 gene.
Since the initial published report in 2014 describing the first four patients diagnosed, many more people have been diagnosed worldwide. Xia-Gibbs Syndrome is a very rare condition, but awareness is beginning to spread.
Xia-Gibbs Syndrome (XGS) is a rare genetic disorder in which the AHDC1 gene is damaged. As a neurodevelopmental disorder, it originates in the brain, causing physical and intellectual disability.
XGS appears within the first year of life with hypotonia (poor muscle tone), sleep apnea and poor feeding. Next there is severe global developmental and expressive language delay. Older children suffer severe intellectual disability and are sometimes classified with symptoms of autism spectrum disorders (ASDs). Some individuals suffer from scoliosis and/or seizures, and there are a subset with behavioral issues, including aggression and self-injurious behaviors.
There is never a family history, so there is usually a ‘diagnostic odyssey’. Many families search for years before finding the cause of their loved one’s symptoms, receiving misinformation and inadequate care along the way. This is why the building of awareness and collaboration between families and scientists that Xia-Gibbs Society promotes is so important.
Some of the common symptoms are listed below (from what we know so far, not everyone with XGS experiences all of these symptoms and the symptoms vary in severity):
- Global developmental delay (reaching developmental milestones later than usual)
- Intellectual disability (which affect a person’s ability to learn, communicate and retain information and undertake daily living activities)
- Hypotonia (low muscle tone)
- Respiratory difficulties, such as laryngomalacia (airway obstruction caused by floppy tissue)
- Sleep apnea (pauses in breathing during sleep)
- Brain changes (these are visible on an MRI scan)
- Some characteristic facial features
- Scoliosis (sideways curvature of the spine)
- Seizures
- Significant overlap with autism spectrum disorders
It is important to remember that this list of symptoms reflects what we have seen so far in individuals diagnosed with XGS. As more individuals receive a diagnosis, doctors will have a clearer understanding of the symptoms experienced by those affected by XGS.
Xia-Gibbs Syndrome is caused by mutations in a gene called AHDC1, which is found on the short arm of Chromosome 1.
There are many different mutations of AHDC1 present in individuals with XGS. At this time it is not known how each of the mutations will affect them. But what they mostly have in common is that there was some change to the sequence of DNA in the AHDC1 gene that has led to a premature stop codon being made, and so the resulting protein is too short.
When proteins are too short, they don’t look the same to the body and can’t be used in the usual way. They can sometimes even cause damage, because they can interfere with other processes of the body.
There are also some people with XGS who, rather than having a shortened or truncated copy of the AHDC1 gene, are missing one copy of the AHDC1 gene completely, due to what is called a ‘deletion’. So far, researchers have not yet determined whether this results in the same symptoms.
Xia-Gibbs Syndrome is very rare and, as it is only recently discovered, it is hard to estimate its frequency of occurrence in the general population.
We are currently aware of more than 390 persons diagnosed with XGS worldwide, from more than 40 different countries.
Scientists estimate that there may be thousands more individuals affected by XGS who are currently undiagnosed. It is likely that the number of diagnosed cases will grow in line with increasing awareness of this rare syndrome.