Chopra-Amiel-Gordon Syndrome (CAGS)

Chopra-Amiel-Gordon Syndrome (CAGS), also known as ANKRD17-related neurodevelopmental syndrome, is a rare genetic disorder that affects the brain, immune system, and kidneys. CAGS is caused by a rare and damaging variant in one copy of the ANKRD17 gene, which plays a key role in brain and organ development, growth, and immune system function.

CAGS is a rare condition first identified in 2021. As awareness and understanding of the condition has grown, more individuals have been diagnosed each year.

Symptoms of CAGS can vary widely. Many children with CAGS receive a diagnosis after a doctor orders genetic testing to better understand developmental delays, seizures (epilepsy), or growth concerns. Standard features of CAGS include:

• Delayed speech and motor development
• Neurodevelopmental conditions such as autism spectrum disorder and ADHD as well as behavioral disorders
• Seizures or abnormal EEG findings
• Feeding difficulties
• Frequent infections, particularly ear or sinus infections
• Kidney issues such as differences in size or shape
• Muscle weakness (hypotonia)
• Subtle but recognizable facial features, such as deep-set eyes, a thin upper lip, and a triangular face shape
• Vision concerns, including nearsightedness, farsightedness, or strabismus

CAGS is caused by a change (pathogenic variant) in one copy of the ANKRD17 gene, which helps regulate how the brain develops, how the immune system responds to infection, and how organs form. Most variants in the ANKRD17 gene happen de novo, meaning they occur spontaneously and aren’t inherited from either biological parent. Researchers are working to better understand whether specific gene variations in the ANKRD17 gene result in distinct symptoms.

Physicians typically diagnose CAGS in children who have a pathogenic variant (a damaging change) in the ANKRD17 gene and show common symptoms of the condition.

At Boston Children’s Hospital, our diagnostic testing may include:

• Whole-exome or genome sequencing
• EEG and brain imaging to assess neurologic features
• Kidney ultrasound and imaging of other organs

Researchers are evaluating whether testing the immune pathway regulated by ANKRD17 could help diagnose CAGS.

There’s currently no cure for CAGS, but many symptoms can be managed with support from a coordinated team of specialists. At Boston Children’s CAGS Clinic, care may include:

• Genetic counseling for families
• Immune system evaluation and infection prevention strategies
• Individualized education planning (IEPs) and behavioral therapies for neurodevelopmental and behavioral concerns, including autism and ADHD
• Kidney monitoring and management of urinary concerns
• Neurologic care for seizures or abnormal EEG activity, and for behavior and tone concerns
• Speech therapy, occupational therapy, and physical therapy
• Surveillance for eye or vision complications

Early diagnosis, intervention, and supportive care for children with CAGS can significantly improve their quality of life and development, especially in communication and social-emotional abilities.

We’re still studying the long-term outcomes of CAGS. However, existing research suggests that children with CAGS show significant progress in language development and social interaction when they receive the appropriate therapies. In addition, a long-term natural history study led by our team is contributing to the understanding of how conditions such as CAGS evolve, which can lead to improved care and support for children and their families.

At Boston Children’s, our CAGS Clinic is the first and only clinic in the world dedicated to children and adults with the condition.

We care for the largest known group of individuals with CAGS, giving families access to the latest medical knowledge, personalized care strategies, and ongoing research opportunities.

Because CAGS affects many parts of the body, our team takes a coordinated, multidisciplinary approach to care. Experts from multiple specialties collaborate to provide individualized, research-driven care, including genetic counseling and opportunities to join international research studies.

We’re committed to working closely with you and your family to deliver compassionate care that supports your child’s long-term health and development.