FOXG1 Syndrome is a rare neurodevelopmental genetic disorder caused by a mutation of the FOXG1 gene. It is usually non-inherited. Prior to 2018, when FOXG1 Syndrome was classified, individuals exhibiting symptoms were often misdiagnosed as having cerebral palsy or autism, or were left undiagnosed. In some cases, individuals were diagnosed as having a congenital form of Rett Syndrome. This is due to the fact that many symptoms, such as being non-verbal, non-ambulatory and having abnormal limb movements, hand wringing, digestive problems, and epilepsy, overlap with Rett Syndrome symptoms. Still today, FOXG1 Syndrome is often described as a congenital form of Rett Syndrome, even though the FOXG1 gene has been identified.
In rare cases, mutations of the FOXG1 gene can be inherited from parents. Otherwise, mutations occur due to a "de novo," or spontaneous, non-inherited mutation. In general, non-inherited genetic mutations are believed to most likely occur at, or in the months before, conception, within a sperm or egg. This is the period of the most cell division, offering the most opportunities for mutations to occur. In some cases, mutations can occur during the formation of an embryo.
In general, non-inherited genetic mutations across any gene within sperm, eggs or embryos can occur for a number of reasons. At times, mutations can occur when cells divide, for unknown reasons. As for known reasons, the most researched include mutations that occur due to exposure to substances than can be toxic to sperm, eggs and embryos such as drugs, alcohol, tobacco, certain medications, and certain chemicals such as BPA (Bisphenol A). Another widely accepted cause includes exposure to viral infections.
There are over 1,000 known cases of FOXG1 worldwide, and growing. This represents one in 8 million people. Given many cases are initially misdiagnosed or undiagnosed, it is quite possible there are tens of thousands of children and adults with FOXG1 Syndrome who remain misdiagnosed or undiagnosed. This can happen for many reasons, but the three most common are:
Yes, FOXG1 Syndrome can be detected in the womb. In most cases, the FOXG1 gene mutation is present throughout the entirety of the pregnancy. The FOXG1 gene, however, is not included in the standard genetic testing panels offered during pregnancy. In fact, most genes that result in rare disorders are not included. If your child shows abnormalities during scans, such as potential microcephaly, your practitioner may recommend genetic testing that may include the FOXG1 gene. Otherwise, in order to include the FOXG1 gene during testing, you'd need to ask your practitioner to have it added. There are many activist groups working to change legislation to include more comprehensive prenatal screening, such as with Every Life Foundation.
Examples of known mutations include:
Each mutation results in a change in the functional amount of FOXG1 protein produced. Furthermore, each mutation's specific details of the mutation affect this production. A deletion, for example, can delete a small segment of the gene or a very large segment, resulting in differing function of the gene. It is important to discuss your child's genetic results with your genetic counselor to understand the specific of your child's genetic mutation.
FOXG1 Syndrome is a neurodevelopmental disorder showing symptoms early in life, or "congenitally," versus a neurodegenerative disorder showing symptoms later and progressively worsening, such as with Rett Syndrome.
A child born with any of the more common FOXG1 mutations suffers a severe lack of motor control alongside severe cognitive impairment. They are nonverbal and cannot walk. They often have seizures, vision issues, an inability to sleep for long stretches, and may rely on feeding tubes and breathing tubes.
There are mutations where there is motor control, often seen with missense mutations, for example. Kids with these mutations can usually walk, talk, and for some, can even hold jobs later in life. However, they have their own set of problems, often including seizures and, at times, severe autism-like behavior.
Below is a list of typical symptoms. Children with the more severe mutations often suffer from all of these symptoms:
None of the FOXG1 mutations have treatments or cures. There are treatments for symptoms, such as epilepsy medication, sleep aids, acid reflux medications, and surgeries to ease breathing, eating, vision or back and spine issues.
Unfortunately there isn't concrete data on this, however it is well accepted that approximately 30% of children die before the age of 5 years old. Oftentimes this is due to an infection that progresses uncontrollably, due to death during a seizure, or sometimes due to unknown reasons, most often occuring overnight during sleep. It is hypothesized that controlling seizures and avoiding overburden with too many medications can help increase life expectancy, in that breathing can come easier.
There are many organizations offering parent support and funding research to cure FOXG1 Syndrome:
----------------------------
For further reading and article sources, see below:
Stay up to date on news and activities!
Stay up to date on news and activities!
The Children's Rare Disorders Fund is dedicated to finding a cure for FOXG1 Syndrome, and replicating successes across as many rare genetic disorders as possible through funding gene, stem cell and/or drug therapy research. Children with rare disorders are often neurologically and physically disabled. They are often unable to walk, talk, feed themselves, nor do much of what we take for granted every day. Founded by parents of a toddler affected by FOXG1 Syndrome, The CRD Fund is one of the few charities in the world in which 100% of every donation is directed to the cause - in this case, to the development of cures and treatments.
.png)