FOXG1 syndrome: Year of the Zebra

FOXG1 syndrome is a rare neurologic condition caused by alterations in the FOXG1 gene. The FOXG1 gene codes for a protein that plays an essential role in early brain development and is particularly important for the formation of the cerebral cortex. It also helps to establish connections between the right and left hemispheres through a large nerve tract called the corpus callosum, and is important for regulating the proliferation and survival of cells in the brain. Alterations in the FOXG1 gene usually occur sporadically, meaning they are typically not inherited from a parent and do not run in families.

Symptoms of FOXG1 syndrome are generally present since early childhood. Most children have severe developmental delays affecting speech and motor skills. They can also have autism-like traits, such as difficulty with social interactions and communication. As they grow older, some children develop acquired microcephaly, which is when there is a deceleration in head growth despite having an average head circumference at birth.

A classic feature of FOXG1 syndrome is the presence of a hyperkinetic movement disorder characterized by involuntary muscle twitching or jerky contractions, as well as choreoathetosis, which is a combination of chorea, or involuntary and irregular spasmodic movements, and athetosis, or involuntary twisting movements. Individuals may also exhibit stereotypies, which are repetitive sounds or movements, like body rocking or finger tapping.

Additionally, the majority of children develop seizures that are often resistant to medication and can evolve into epilepsy syndromes. In addition to neurologic symptoms, FOXG1 syndrome is associated with feeding difficulties and gastrointestinal problems like reflux and constipation; as well as sleeping problems like difficulty falling or staying asleep and unexplained episodes of crying.