Coffin-Lowry Syndrome

What Causes Coffin-Lowry Syndrome?

Coffin-Lowry syndrome is caused by an abnormal change (mutation) in a gene called the RPS6KA3 gene. This gene is responsible for producing a protein (RSK2) crucial for proper cell functioning. Scientists don’t fully understand the function of the RSK2 protein, but it seems to be particularly important in the function and survival of brain cells. It may play a significant role in brain functions such as long-term memory and learning.

The RPS6KA3 gene is on the X chromosome. Females have two X chromosomes, and males have only one X chromosome. CLS develops in a dominant pattern, meaning that the disorder will develop if even one mutated gene is present. However, females can have one mutated copy of the gene and one normal copy. In these cases, the normal gene may compensate to a degree for the mutated gene in the production of the RSK2 protein. Since males with the mutated gene do not have a normal copy to compensate, their cells’ production of the protein may be more significantly impacted. This may explain why CLS symptoms are often more severe in males.

Is Coffin-Lowry Syndrome Hereditary?

Most cases of Coffin-Lowry syndrome are not inherited. In up to 80 percent of cases, the RPS6KA3 gene mutation appears to occur spontaneously during fetal development. In some cases, no detectable RPS6KA3 gene mutation is present.

In 20-30 percent of cases, children with CLS have a relative with the disorder. In these cases, there may be an inherited component.

How Is Coffin-Lowry Syndrome Detected?

Facial features in CLS are often distinctive, but they might not be recognized at birth. A broad forehead might be noticeable when the baby is born, but it may be mistaken for a congenitally enlarged head (macrocephaly). Facial features are usually more pronounced in boys, and delays in growth and intellectual development are often apparent by early childhood. Features and delays are often less significant in girls, making early diagnosis more difficult.

How Is Coffin-Lowry Syndrome Diagnosed?

Doctors may suspect CLS when a child exhibits features of the disorder and is experiencing developmental delays. A diagnosis of Coffin-Lowry syndrome can be confirmed using tests and exams to look for the disorder’s distinctive features and genetic signature.

Common diagnostic steps include:

• X-rays or imaging exams to detect skeletal or other abnormalities
• Tests to measure the activity of the RPS6KA3 protein. This test cannot detect the syndrome in females.
• Genetic testing to look for RPS6KA3 gene mutations. Not all children with CLS have a detectable mutation, so a negative test does not rule out the disorder.

PLEASE CONSULT A PHYSICIAN FOR MORE INFORMATION.

How Is Coffin-Lowry Syndrome Treated?

Coffin-Lowry syndrome has no cure. Standard treatment approaches aim to lessen the severity of symptoms, prevent complications, and improve quality of life.

Common treatments include:

• Anti-convulsant medications to prevent SIDEs
• Physical therapy
• Speech therapy
• Occupational therapy
• Monitoring of kyphoscoliosis, which can lead to life-threatening heart problems
• Regular vision, hearing, and dental exams
• Avoidance of situations that could cause SIDEs

How Does Coffin-Lowry Syndrome Progress?

Some of the symptoms of CLS are progressive and can lead to potentially life-threatening complications. When kyphoscoliosis is severe, serious heart or respiratory complications can result.

Other potential long-term complications include:

• Broken bones or injuries from falls due to motor impairments
• Injuries related to SIDEs
• Depression
• Hearing or vision loss
• Dental problems

How Is Coffin-Lowry Syndrome Prevented?

There is no known way to prevent Coffin-Lowry syndrome when the disorder-causing gene mutations are present. A woman who has CLS herself has a 50 percent chance of passing the mutation to her child with each pregnancy. Any of her male children who inherit the mutation will have the disorder. Any female children who inherit the mutation will be carriers like the mother and will be at risk of developing symptoms of CLS. A woman with CLS or a family history of the disorder may want to consult a genetic counselor before becoming pregnant.

Coffin-Lowry Syndrome Caregiver Tips

• Educate yourself about CLS. CLS is a life-long disorder, and both you and your child will have to learn how to live with its challenges. The more you know about how the condition affects your child, the better you’ll be able to help them thrive.
• Be active in your child’s medical care. Many of the symptoms of CLS can lead to severe complications if they’re not handled correctly. So follow your doctor’s advice, and be sure to stick to a schedule of regular checkups and doctor visits.
• Reach out to the CLS community. Online support groups can give you sources of information and answer your questions. Perhaps most importantly, they can also remind you that you’re not alone in living with CLS.

Many people with Coffin-Lowry syndrome also suffer from other brain and mental health-related issues, a condition called co-morbidity. Here are a few of the disorders commonly associated with CLS:

• People with CLS are at increased risk for stroke.
• About 1 in 20 people with CLS also suffer from epilepsy.
• Female carriers of CLS are at increased risk of bipolar disorder, schizophrenia, and other psychoses.

Coffin-Lowry Syndrome Brain Science

Scientists are currently working to understand better the role the RSK2 protein plays in brain function. Some researchers believe that animal experiments may provide clues to the mechanism of a disorder like CLS in the human brain.

Studies of mice whose RSK2-producing gene has been turned off found that the mice experienced problems with both cognitive and emotional behaviors. The mice had defects in their memories and learning abilities, but they also seemed to show changes in their behavior in areas such as anxiety and depression. The studies suggest that the effects of CLS in human brains may go beyond the cognitive symptoms that have already been noted.

Coffin-Lowry Syndrome Research

Title:  Personalized Spine Study Group (PSSG) Registry (PSSG)

Stage: Recruiting

Contact: Christopher Kleck, MD

University of Colorado, Denver

Denver, CO

The registry follows patients during their standard of care visits. During a standard of care visit, a study subject will be required to answer questions about themselves and fill out patient-reported outcome questionnaires. Spinopelvic measurements will be collected from the standard of care x-rays. This registry is only used to address patient outcomes sagittal profile through the pre-operative, plan, and postoperative events. Patient outcomes in subgroups are defined by surgery performed, comorbidities, radiographic measurement, or other outcome variables.  

Title: Prognosis Factors for the Treatment of Pectus Carinatum With a Dynamic Compression System (Pectusdyn)

Stage: Recruiting

Contact: Aurélien SCALABRE

CHU de Saint-Etienne

Saint-Etienne, France

Pectus carinatum is a deformation of the thoracic wall causing an aesthetic prejudice. Since 2011, our team uses a dynamic compression system to treat this deformation. It is a harness that the patient wears all day long for an average duration of 1 year, which remodels the chest by exerting moderate pressure on it. The local cohort is one of the largest in the world. The few previous publications have shown the validity of this method, but the prognosis factors for the success of this innovative treatment are not yet identified.

The principal investigator hypothesizes that the success or failure of the treatment depends on several parameters assessable before treatment, such as the patient’s age, gender, initial correction pressure, symmetry, or not of the deformation.