Coffin-Siris Syndrome

Coffin-Siris syndrome (CSS) is a rare genetic condition that can affect many parts of your child’s body. Signs and symptoms vary widely, but most children will experience:

• Underdeveloped or missing fifth (“pinky”) fingers, toes or nails
• Developmental delays and learning difficulties
• Distinct facial features
• Feeding problems
• Frequent infections

CSS looks different in every child. Treatment focuses on managing your child’s specific needs and helping them grow and develop over time. Another name for the condition is fifth digit syndrome.

What are the symptoms of Coffin-Siris syndrome?

Healthcare providers look at Coffin-Siris syndrome on a spectrum. That means symptoms and their severity can be very different from one child to another. Some children have mild differences, and others have more complex medical needs.

Facial features

Many children with Coffin-Siris syndrome have facial features that may look different from what’s typical. Providers sometimes call these “coarse facial features.” This doesn’t mean anything negative. It’s just a medical term providers use to describe certain shared traits. These may include:

• A wide nose with a flat bridge
• Thick eyebrows and long eyelashes
• A wide mouth with full lips
• A longer space between their nose and upper lip

Hair differences are also common. These features may be subtle at birth and become more noticeable as your child grows. Your child might have:

• Thick hair on their face, back or shoulders
• Thin or sparse hair on their scalp

Fingers and toes

One of the most common signs of Coffin-Siris syndrome involves your child’s fifth fingers and toes (their “pinkies”). They may have:

• Small or underdeveloped pinky fingers or toes
• Missing or underdeveloped nails on their fifth digits

Feeding and growth

Feeding challenges and growth issues are very common, especially in babies and young children. You might notice:

• Trouble feeding
• Poor coordination while eating
• Slow weight gain
• Short stature
• A small head (microcephaly)

Development, learning and behavior

Most children with Coffin-Siris syndrome have some level of developmental delay or intellectual disability. This can range from mild to more severe. Your child may:

• Reach milestones later than expected
• Have trouble with muscle strength or coordination
• Learn at a slower pace

Some kids with Coffin-Siris syndrome talk. But speech delays are common. Children with the condition usually understand more than they can say. First words may come later, and building sentences can take time. Some children have limited or no spoken language, especially if delays are more severe.

Behavioral issues with Coffin-Siris syndrome can include:

• Hyperactivity
• Trouble focusing
• Aggressive behavior

Other organ system-related issues

Children with Coffin-Siris syndrome may have issues in other parts of their body. Symptoms and conditions may include:

• Respiratory infections
• Low muscle tone
• Loose joints
• Scoliosis
• Hearing loss
• Seizures
• Heart defects

Coffin siris syndrome causes

A change (variant) in a gene causes Coffin-Siris syndrome. The most common gene involved is ARID1B. But changes in one of 13 other genes can also cause the condition. These include:

• ARID1A
• SMARCA4
• SMARCA2
• SMARCB1
• SMARCE1
• SOX11

About 4 out of 10 people with CSS have normal genetic testing. So, there are likely more genes yet to be discovered.

These genes help control how other genes turn “on” and “off.” Your body has many instructions, but it doesn’t use them all at once. These genes help decide which instructions to use and when. When there’s a change in one of these genes, it can disrupt the process. That’s why CSS can affect many parts of your child’s body.

Is Coffin-Siris syndrome inherited?

Coffin-Siris syndrome follows an autosomal dominant inheritance pattern. That means you only need one copy of the changed gene to develop the condition. But most cases of Coffin-Siris syndrome aren’t inherited. Instead, the gene change usually happens by chance. A new, or “de novo,” variant forms early in fetal development. If a person with CSS were to have a child, then the chance would be 50%.

Nothing you did before or during pregnancy caused this condition. These gene changes happen randomly. Researchers are still learning more about Coffin-Siris syndrome and the related genes.

Risk factors

Researchers don’t know why, but Coffin-Siris syndrome appears to affect females more frequently.

It’s rare, but sometimes an unaffected parent can pass the gene change down. If your child has CSS, you may want to consider genetic counseling. It can help you understand what caused the condition and the chances of it happening again.

How doctors diagnose Coffin-Siris syndrome

Your child’s healthcare provider may suspect Coffin-Siris syndrome based on their symptoms and physical features. Signs can vary, so diagnosis often happens over time as more features become clear.

The only way to confirm Coffin-Siris syndrome is through genetic testing. This test looks for changes in the genes known to be linked to CSS.

If a known gene change runs in your family, testing during pregnancy may be an option. These tests include chorionic villus sampling (CVS) and amniocentesis.

After diagnosis, your child’s provider may recommend other tests to better understand how Coffin-Siris syndrome affects their body. These tests may include:

• MRI scan
• Hand X-ray
• Echocardiogram
• Developmental evaluations
• Hearing and vision tests
• Feeding and nutrition evaluations

How is Coffin-Siris syndrome treated?

There’s no cure for Coffin-Siris syndrome. Treatment is ongoing and may change as your child grows. It focuses on managing your child’s symptoms and helping them reach their full potential.

Therapies and early support

Early intervention is a key part of treatment. Your child may benefit from:

• Speech therapy
• Physical therapy
• Occupational therapy
• Special education services, including individualized education plans (IEPs)

Some children may also use tools like communication devices, eyeglasses or hearing aids.

Feeding and nutrition support

Feeding problems are common in children with Coffin-Siris syndrome. Treatment may include:

• Feeding therapy
• Changes to food preparation or feeding methods
• G-tube placement for extra nutritional support

Medical treatments and procedures

Treatment may also include care for specific symptoms or conditions, like:

• Antibiotics for infections
• Shunt placement for brain-related issues
• Surgery for skeletal or facial differences

Researchers are studying new approaches, like gene therapy. But right now, it’s unclear how these treatments might work.

When should my child see their healthcare provider?

If your child has Coffin-Siris syndrome, regular checkups are an important part of their care. These visits help providers track your child’s growth and development. During these appointments, their provider will:

• Check growth and nutrition
• Monitor development and learning
• Watch for seizures, sleep problems or infections
• Assess movement and daily living skills

You should also keep up with routine care, like vision, hearing and dental checkups.

In general, don’t wait for something to feel “wrong.” Ongoing care helps catch concerns early and ensures your child gets the right support as they grow.

What is the life expectancy of someone with Coffin-Siris syndrome?

There isn’t enough long-term research to know exactly how Coffin-Siris syndrome affects life expectancy. But many people with CSS can live into adulthood. Adults with this condition have been reported in their 20s, 30s and beyond, including at least one person who lived into their late 60s.

Outcomes can vary widely depending on your child’s symptoms and overall health. In rare cases, serious complications, like aspiration pneumonia and seizures, can affect life expectancy. Children who need significant breathing support or have complex medical needs may have a higher risk of serious complications, especially at younger ages.