Coffin-Lowry Syndrome

What is Coffin-Lowry syndrome?

Coffin-Lowry syndrome (CLS, or Coffin syndrome) is a rare condition that can affect many parts of the body. It’s congenital, meaning that people are born with it.

CLS often causes unusual facial features, intellectual disability, abnormal skeletal development, short stature and weak muscle tone. People with the condition also might have large hands with short, thin (tapered) fingers.

Some affected people also experience stimulus-induced drop episodes (drop attacks). During the episodes, they are conscious but collapse suddenly in response to an unexpected noise, event or emotion.

People inherit (passed down from one generation to another) Coffin-Lowry syndrome — most often on the X chromosome. But most people with the condition have no family history of the condition meaning they occur sporadically.

How common is Coffin-Lowry syndrome?

CLS is rare. Scientists estimate that it affects 1 in 50,000 to 1 in 100,000 people. Approximately 70% to 80% are sporadic cases.

Who might get CLS?

CLS occurs in both males and females, but symptoms are generally more severe in males and people assigned male at birth. Specifically, males with CLS often have severe intellectual disabilities. But affected females range from having average cognitive skills to mild, moderate, or severe intellectual disability.

What causes CLS?

A mutation in a gene named RPS6KA3 is the usual cause of Coffin-Lowry syndrome. The gene is responsible for making a protein that helps cells communicate with each other. With the gene mutation, the body produces less of that protein. But scientists don’t fully understand how the protein is linked to Coffin-Lowry syndrome.

Some people have CLS without a detectable RPS6KA3 gene mutation. In those cases, scientists don’t yet understand what causes the condition.

What are the symptoms of Coffin-Lowry syndrome?

Symptoms of Coffin-Lowry syndrome vary widely from person to person and are usually more severe in males. They affect many different parts of the body and become more obvious as a person gets older.

CLS facial features often include:

• Wide-set eyes with slits that slant downward.
• Oversized ears that are lower than usual.
• Prominent forehead, eyebrows and chin.
• Upturned nose with a broad bridge and flared nostrils.
• Wide mouth with thick lips.

People with Coffin-Lowry syndrome also have distinctive hands:

• Double-jointed fingers.
• Fingers that are thick at the base and then taper toward the tip.
• Large, soft hands.

Skeletal issues include:

• Curved spine (kyphosis or scoliosis) that gives the appearance of a hunched back.
• Dental abnormalities, such as a misshaped mouth or missing teeth.
• Pointed or sunken breastbone.
• Shorter long bones (for example, thigh bone, shin bone, upper arm).
• Short stature (height).
• Microcephaly (small head).

Other symptoms can include:

• Developmental delays and intellectual disability.
• Drop attacks.
• Hearing loss.
• Loose, stretchy skin.
• Problems with the heart, liver or kidneys.
• Short big toes.
• Speech problems.
• Weak muscle tone with muscle weakness.

How is Coffin-Lowry syndrome diagnosed?

A healthcare professional can diagnose Coffin-Lowry syndrome based on:

• Observation of the classic symptoms.
• Blood test or cheek swab to confirm a genetic mutation in the RPS6KA3 gene.
• X-rays to see the effects on the spine, fingers and long bones.
• Neuroimaging studies to look closely at the brain, although this is not conclusive.

Is there a cure for Coffin-Lowry syndrome?

There is no cure for this condition or any specific treatments. The goal is to manage the condition, reduce symptoms and live life as fully as possible.

People with CLS may need regular visits with a variety of medical specialists, such as:

• Audiologists (hearing).
• Cardiologists (heart).
• Neurologists (nervous system).
• Ophthalmologists (vision).
• Orthopedists (joints, bones and spine).
• Dental specialists.
• Occupational therapists to help improve performance with daily activities, such as eating and writing.
• Physical therapists to improve strength and movement.
• Speech therapists for communication delays.

For drop episodes, a healthcare provider may prescribe anticonvulsant medications, normally used to control seizures, or anti-anxiety medications.

Skeletal deformities may require surgery.

Your healthcare provider also may recommend genetic counseling.

Can I prevent CLS in my child?

Scientists don’t know what causes the genetic mutation or sporadic cases. Therefore, there is no way to prevent Coffin-Lowry syndrome. A woman with the condition has a 50% chance of passing it on to her baby. Prenatal genetic testing can check for the gene mutation. Your healthcare provider may also recommend genetic counseling for close family members.

What can I expect if my child or I have this condition?

The outlook for people with CLS varies widely. Prognosis depends on the parts of the body affected and how severe those effects are.

Is Coffin-Lowry syndrome fatal?

The condition can reduce lifespan. Some studies have reported that about 13.5% of males and 4.5% of females died at an average age of 20.5 years.

What else can I ask my healthcare provider about CLS?

If you or your child has CLS, consider asking your healthcare provider the following questions:

• What parts of the body are affected?
• Are any of the effects life-threatening?
• What specialists should I see, and how often?
• Do you recommend medications or surgery?
• Are there any support groups that can help us cope with this condition?
• Do you recommend genetic counseling for our situation?
• Should other people in our family get genetic testing?

A note from Cleveland Clinic

Coffin-Lowry syndrome (CLS) is a rare condition that can affect many parts of the body. Symptoms vary but often involve unusual facial features, skeletal abnormalities, and intellectual disability. If you or your child have CLS, specialists can help determine what body systems are involved, help to manage the effects and offer more information on the heritability of this condition.