What is FOXG1 Syndrome?

FOXG1 Syndrome is a rare 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 either misdiagnosed, left undiagnosed, or  were diagnosed as having a congenital form of Rett Syndrome. This is due to the fact that many symptoms, such as abnormal movements, hand wringing and digestive problems, 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.

Domenico practices sitting at 20 months old. Physical therapy can prevent muscle atrophy. When we find a cure, he will be better positioned to learn to sit, stand and walk.

Why does it happen?

In some cases, it can be inherited from parents. Otherwise, it occurs due to a "de novo," or spontaneous, non-inherited mutation. It is thought to happen at or before conception, within a sperm or egg. There is no current research to explain the cause of a de novo mutation.

How rare is FOXG1 Syndrome?

There are approximately 1,000 known cases of FOXG1 worldwide. However, given many cases were initially misdiagnosed, it is quite possible there are tens of thousands of children with FOXG1 Syndrome who remain misdiagnosed or undiagnosed. This can happen for many reasons, but the three most common are:

  • Anyone diagnosed prior to the discovery and classification of FOXG1 Syndrome was often diagnosed with another disorder
  • There are many genetic tests that don't include every mutation of the FOXG1 gene. As such, without genetic proof, FOXG1 children are often misdiagnosed as having Cerebral Palsy or Autism
  • Unfortunately, many times doctors do not suggest genetic testing and instead diagnose with Cerebral Palsy or Autism

Can it be detected before birth?

Yes! Since FOXG1 Syndrome is present at or before conception, the gene mutation is present throughout the full pregnancy. Unfortunately, however, the FOXG1 gene is not included in the standard genetic testing panels offered during pregnancy. Infact, most genes that result in rare disorders are not included. In order to include the FOXG1 gene during testing, you'd need to ask your practitioner to have it added. Or, you can ask for what's called a "full genome sequencing," which will check every known gene. Full genome sequencings are generally not covered by insurance, and can be expensive. Rapid Genome Sequencing is a new method of screening, still in it's infancy. There are many activist groups working to change legislation to include better prenatal screening, such as with Every Life Foundation.

What are the known mutations?

Known mutations include:

  • Deletion
  • Duplication
  • Nonsense
  • Frameshift
  • Missense

Each mutation produces a different amount of FOXG1 protein. Furthermore, each mutation's specifics produces a different amount of protein. A deletion, for example, can delete a small segment of the gene or a very large segment, resulting in little or no FOXG1 protein. As such, it is important to discuss your child's genetic results with your genetic counselor.

What are the signs and symptoms?

FOXG1 Syndrome is a neurodevelopmental disorder showing symptoms early in life, or "congenitally," versus a neurodegenerative disorder showing symptoms later and progressively worsening.

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 due to feeding issues.

There are a couple of mutations where there is motor control, often seen with missense mutations. Kids with these mutations can usually walk, talk, and for som, can 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:

  • Excessive crying
  • Irritability
  • Lack of purposeful hand movements
  • Abnormal movements of arms and legs that interfere with purposeful movement
  • Inability to walk or limited mobility
  • Low muscle tone
  • Inability to fall asleep
  • Sleep disturbances while asleep
  • Inability to sleep for long periods
  • Inability to talk or limited communication skills
  • Cortical vision impairment
  • Strabismus (eye crossing, often requiring surgery)
  • Acid reflux
  • Feeding problems
  • Teeth grinding
  • Microcephaly
  • Partial or complete agenesis of the corpus callosum
  • Reduced folds on the surface of the brain
  • Reduced brain white matter
  • Seizures / Epilepsy

Heather Olson, MD, MS, Neurologist at Boston Children's and Instructor of Neurology at Harvard Medical School, gives an overview of FOXG1 Syndrome.

Are there treatments or cures?

None of the FOXG1 mutations have treatments or cures. There are treatments for symptoms, such as epilepsy medication, sleep aids, acid reflux medications, etc.

What is the life expectancy for FOXG1 Syndrome?

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 overnight can come easier.

Where can I find more info?

There are many organizations offering parent support as well as funding research to cure FOXG1 Syndrome:


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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.