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Coffin-Lowry Syndrome (CLS)
Sunday, 20 July 2003
Thursday, 19 May 2005


Coffin-Lowry syndrome (CLS) is a genetic disorder characterized by mental disabilities, low muscle tone, and differences of the head, face, and skeleton.


Coffin-Lowry syndrome occurs in about 1 in 40,000 to 1 in 50,000 births, but this may be an underestimate. CLS occurs equally in both males and females, however, males are more severely affected than females.

Signs and Symptoms

Coffin-Lowry syndrome is present from birth but may not be recognized right away. CLS is characterized by severe mental retardation in males. Females vary in intellect from normal to severely retarded. Children with CLS are often described as happy and pleasant although this varies from child to child. Length and weight at birth are usually normal. However, growth problems develop and children with CLS become short and underweight. Dental problems are common. Teeth may not come in on time or fall out too early. They may be small, abnormally shaped, or crooked. About 10-20% of children may experience drop-attacks starting in mid-childhood to the teenage years. These are brief collapses with no loss of consciousness due to excitement from touch or sound. There are several other symptoms that can be associated with CLS. At least 47% of males and 32% of females develop progressive kyphoscoliosis (abnormal curvatures of the spine). This is one of the most troubling symptoms of the long-term care of individuals with CLS and can be so severe that it causes difficulty breathing. About 14% of males and 5% of females have heart disease. Some children may be at risk of hearing and vision problems. As children get older, there are typical facial features that are seen especially in males. Females have less striking physical features and may appear normal. The following characteristics are variable and not all are seen in every individual. The forehead and eyebrows are prominent. Eyes may be widely spaced and slant downward. The nose is thick causing the openings to be small and the bridge of the nose is low. The mouth is large and children usually keep their mouths open. The lips are thick and the lower lip pouts. The ears and chin appear large. Hands are short, soft, and fleshy. Fingers are wide at the base and small at the tips with small fingernails. The chest wall may be abnormally shaped. They may have flat feet.

Possible Causes

About 65% of cases of Coffin-Lowry syndrome is caused by changes (mutations) in the RPS6KA3 gene. This gene is located on the X chromosome. There are still many cases of CLS where the exact cause is unknown. CLS is an X-linked dominant disorder. Girls have two X chromosomes. Boys have one X chromosome and one Y chromosome. If the RPS6KA3 gene has a change (mutation) on one of the X chromosomes, the child will have CLS. Since males only have one X chromosome, they have more severe symptoms. Since females have two X-chromosomes, they have one normal X chromosome and one abnormal X chromosome. Because they still have one X chromosome that is normal, they often have milder symptoms.


Coffin-Lowry syndrome is first suspected when the child shows delays in development. It is usually diagnosed based on the physical features listed above. However, it is hard to diagnose CLS in infants because the physical characteristics are mild and may be similar to other syndromes. Because so many genetic conditions are associated with developmental delay, a karyotype is often performed to check for abnormal chromosomes. This test may be normal in patients with CLS. The diagnosis can be confirmed with genetic testing of the RPS6KA3 gene to look for changes (mutations).


There is no cure for Coffin-Lowry syndrome. Treatment is geared toward the child’s symptoms. Physical therapy is helpful for muscle movement and coordination. Speech therapy is important to improve communication skills. Special education classes should be aimed at promoting mental and overall developmental abilities. Hearing and vision should be screened. The heart should be checked for abnormalities. Children should be monitored for kyphoscoliosis, the abnormal curvatures of the spine. This may need treatment with back braces or back surgery. It is important to prevent the curvatures from becoming so severe that the heart and lungs become affected. Caution should be taken to avoid any stimuli that can trigger drop-attacks so that these events can be avoided or reduced in frequency. The environment should be made safe in case a drop-attack does occur. Anti-seizure medication is sometimes used to prevent or lower the occurrence of the attacks. Other medications, such as risperidone, may be used to help with other unwanted behaviors that may injure the child.


The prognosis for children with Coffin-Lowry syndrome depends on the severity of the symptoms. Many of the facial and skeletal features become more noticeable as the child gets older, and some of the motor and coordination problems aren’t evident until late childhood. Early treatment of the child may improve the developmental and mental disabilities. Premature death is increased in individuals who have severe cardiac problems, respiratory complications, or severe progressive kyphoscoliosis.

Connect with other parents

In the spirit of community and support, Madisons Foundation offers the unique service of connecting parents of children with rare diseases. If you would like to be connected to other parents of children with this disease, please fill out this brief form.


The Coffin Lowly Syndrome Foundation
This has great information, helpful links, frequently asked questions, articles, contact information, and support groups.

National Institute of Neurological Disorders and Stroke
This website has information about the disease and ongoing clinical research trials.

Google Search for Coffin-Lowry Syndrome (CLS)

References and Sources

Gene Reviews. Coffin-Lowry syndrome. McKusick V. OMIM. Coffin-Lowry syndrome.