What to know about Coffin-Lowry syndrome

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CLS is a genetic condition that typically results in intellectual disability and several other possible physical symptoms, including tapered fingers, downward-slanting eyes, and delayed bone development. Evidence suggests that CLS affects an estimated 1 in 40,000—50,000 people.

While the condition usually affects males and females in equal numbers, males with CLS often have more severe learning disabilities and more pronounced facial symptoms than females with the condition. This is due to the gene alteration that results in CLS occurring on the X chromosome. Therefore, symptoms are usually more severe in males as they typically only have one X chromosome.

CLS is an example of a genetic condition, which occurs due to changes in the DNA sequence. CLS occurs when there is an alteration in the RPS6KA3 gene. This gene is present on the X chromosome, which is a sex chromosome.

CLS follows an X-linked dominant inheritance pattern. As males typically only inherit one X chromosome, a variant in their only copy of this gene is sufficient to cause the condition. Females typically inherit two X chromosomes. However, having an alteration in one of the two copies of the gene is enough to cause CLS due to its dominant inheritance pattern. This is also why females usually experience less severe symptoms of CLS.

The RPS6KA3 gene is responsible for providing instructions for making a protein known as ribosomal S6 kinase 2. This protein helps regulate the activity of certain genes and has a role in signaling within cells. It is also responsible for learning, forming long-term memories, and the survival of nerve cells. As such, while researchers are unsure of the exact mechanism, producing little to none of this protein likely results in CLS symptoms.

However, some people with features of CLS do not possess alterations in the RPS6KA3 gene. In such cases, researchers are unsure of the exact cause of the condition.

Children born from a biological mother known to have a copy of a gene variation for CLS are at a 50% risk of inheriting the disorder. However, evidence suggests that around 70–80% of people with CLS have no family history of the disorder. Between 20% and 30% of people with CLS have more than one additional affected family member.

CLS symptoms can vary from person to person, and the severity of symptoms can also vary. Below are some of the common characteristics of CLS.

Intellectual disability

People with CLS often have intellectual disabilities. Males with CLS often have severe to profound intellectual disabilities. However, there are also some reports of males with mild intellectual disabilities. Females with CLS tend to have mild to moderate intellectual disabilities.

Characteristic head and facial features

There are some characteristic head and facial features that commonly occur in people with CLS. These features often become more apparent as the person ages. Common head and facial features of CLS include:

• a prominent forehead
• a prominent brow ridge with thick eyebrows
• widely spaced, down-slanted eyes
• a broad nose
• protruding nostrils
• an underdeveloped upper jaw bone
• large, low set ears

Skeletal problems

Skeletal problems may also occur in people with CLS. These can include:

• an excessive curvature of the spine
• an atypical prominence of the breast bone, often known as pigeon chest or pectus carinatum
• dental problems
• short, hyperextensible, tapered fingers

Other possible symptoms

Other possible features of a person with CLS may include:

• short stature
• feeding problems
• respiratory problems
• hearing impairment
• awkward gait
• heart and kidney problems

Around 20% of people with CLS also experience stimulus-induced drop attacks (SIDAs). A SIDA occurs when unexpected stimuli or excitement triggers a person to briefly collapse while remaining conscious.

A doctor may suspect an infant has CLS according to distinctive physical symptoms. These can include the characteristic head and facial features and other physical symptoms.

Doctors may then use certain tests to confirm their diagnosis. A doctor may use molecular genetic testing to diagnose CLS. They can use a blood specimen or a cheek swab to carry out the genetic test. If the test results show an alteration in the RPS6KA3 gene, they can then confirm that a person has CLS.

Currently, there is no cure for CLS. There is also no single, standard treatment for people with the condition. Instead, medical professionals will create a treatment plan to help support a person in their daily life and help tackle certain CLS symptoms. It is also advisable for them to have regular cardiac, hearing, and visual examinations.

A person with CLS may make use of the following treatment options:

• Physical therapy: Physical therapy can help a person with CLS overcome certain physical symptoms of the disorder, such as spinal curvature.
• Speech therapy: A person with CLS may undergo speech therapy to help them improve the way they communicate with those around them.
• Occupational therapy: An individual with CLS may use occupational therapy to help them carry out daily activities and gain independence.
• Medication for SIDAs: Certain medications may help prevent SIDAs from occurring. Medications may include antiseizure medications and benzodiazepines.

If treatments for SIDAs are ineffective, a person may have to wear a protective helmet to protect their head. They may also use a wheelchair to prevent falling and injury.

The prognosis for CLS is different from person to person. The severity of someone’s symptoms can greatly affect their outlook. Early intervention can improve the outlook of people with CLS. In some cases, CLS can reduce a person’s lifespan. Evidence suggests that around 13.5% of males and 4.5% of females with CLS died at an average age of 20.5 years.

CLS is a rare genetic disorder that affects roughly 1 in 40,000—50,000 people. It typically causes intellectual disability and several other physical symptoms. Some physical symptoms of CLS may include tapered fingers, downward-slanting eyes, and delayed bone development.

CLS affects females and males equally. However, as it follows an X-linked dominant inheritance pattern, males often experience more severe symptoms. While there is currently no cure for CLS, treatment options are available that can help manage symptoms and improve quality of life.