Chopra-Amiel-Gordon syndrome: Year of the Zebra 2024

Chopra-Amiel-Gordon syndrome, or CAGS for short, also known as ANKRD17-related neurodevelopmental syndrome, is a rare genetic condition that primarily affects the development of the brain, eyes, face, and limbs.

CAGS is caused by mutations in the ankyrin-repeat domain-containing protein 17, or ANKRD17, which is a type of protein structure involved in many cellular functions. Ankyrin repeat proteins have a unique shape that allows them to act like hooks, connecting them with other proteins to help in the formation of more complex structures. It is thought that ANKRD17 is involved in the development of blood vessels, yet, how the mutation in this protein leads to the clinical manifestations of CAGS is currently unknown.

Most cases of CAGS come from de novo mutations, meaning they arise on their own and are not inherited. However, several cases of familial inheritance have also been reported.

Typically, individuals with CAGS have unique facial features, which include a triangular face shape, high anterior hairline, low-set ears, a thin upper lip, and deep-set or almond-shaped eyes. Less common features include scoliosis and cleft lip or palate, which are openings in the upper lip or roof of the mouth, respectively.

Individuals with CAGS also typically have varying degrees of learning disabilities and delays in reaching developmental milestones, such as sitting, crawling, and speaking. Additionally, they may have difficulties with tasks that require coordination and balance, like walking. Some individuals may experience epilepsy and have eye abnormalities; and there may also be neurobehavioral symptoms, like repetitive behaviors and difficulty with social interactions.

Finally, children with CAGS tend to have feeding problems and frequent respiratory infections, which, if left untreated, can result in failure to thrive and decreased weight gain.