An Overview of Coffin-Lowry Syndrome

A Rare Congenital Disorder

In This Article

Coffin-Lowry syndrome is a rare neurological disorder characterized by mild to profound intellectual disability, as well as developmental delays in growth and motor coordination. Usually more severe in men, affected individuals have distinctive facial features such as a prominent forehead and widely-spaced downward-slanted eyes, a short, wide nose, and soft hands with short fingers. In many cases, people with this condition experience abnormal curvature of the spine, shortness of stature, and microcephaly (an abnormally small head).

Symptoms

The symptoms of Coffin-Lowry syndrome, which tend to be more severe in men, become more prominent with age. These include:

  • Intellectual Disability: The scope of this symptom ranges from mild to profound intellectual disability, with some people with this condition never developing speech abilities.
  • Broad Facial Features: Especially prominent in males and most visible in late childhood, those with Coffin-Lowry syndrome have a prominent forehead, widely-spaced and downwardly slanted eyes, a shorter, wide nose, as well as a wider mouth with thicker lips.
  • Large, Soft Hands: Another feature of this condition is larger, soft hands with shorter, tapered fingers.
  • Stimulus Induced Drop Episodes: Arising in childhood or adolescence in some people, some with this condition may experience collapse in response to loud sounds or noise.
  • Spine Curvature: Many with Coffin-Lowry syndrome experience either scoliosis (lateral curvature) or kyphosis (outward rounding) of the spine.
  • Microcephaly: An abnormally small-sized head—microcephaly—is a frequent symptom.
  • Skeletal Abnormalities: Those with this syndrome may have double-jointedness, a shortened big toe, thicker facial bones, shortening of longer bones, and a pointed or sunken breast-bone.
  • Loss of Muscle Mass: Poor formation of musculature is often observed in those with Coffin-Lowry syndrome.
  • Progressive Spasticity: This is defined as the tensing up of certain muscle groups, a problem which can worsen over time.
  • Sleep Apnea: A frequently recorded symptom of this condition is sleep apnea, which is snoring and/or problems breathing while asleep.
  • Increased Risk of Stroke: There’s evidence that the population of those with Coffin-Lowry syndrome are at an increased risk of dangerous stroke, due to interruptions in blood flow to the brain.
  • Increased Mortality: Studies have shown that those with this condition may end up seeing a significantly reduced lifespan.

As noted above, these symptoms do vary a great deal, with some becoming much more pronounced than others.

Causes

A congenital condition, Coffin-Lowry syndrome arises due to mutations in one of two specific genes of the X chromosome: RPS6KA3 and RSK2. These genes help regulate signaling between cells in the body, especially those involved in learning, long-term memory formation, and overall lifespan of nerve cells. Furthermore, it’s been established that they help control the function of other genes, so one mutation can lead to a cascade effect. Ultimately, though, more research is needed to ascertain the exact mechanism of this mutation as it relates to the syndrome.

Notably, this condition follows what’s called an “X-linked dominant pattern,” meaning the affected RPS6KA3 or RSK2 gene is on the X chromosome (one of the two sex-linked chromosomes). Only one mutation of the gene is sufficient to cause Coffin-Lowry syndrome, hence its “dominance.” In this pattern of inheritance, fathers with the syndrome cannot pass it to sons (since sons receive a Y chromosome from the father, with their X chromosome coming from their mother). A majority of cases—between 70 and 80 percent—arise in those who have no family history of the syndrome.     

Diagnosis

Initial diagnosis of Coffin-Lowry syndrome involves assessment of physical features; doctors will seek out physical features endemic to the condition, while noting other developmental issues and impairments. This initial work is then aided via imaging techniques, usually X-ray or MRI, of the brain. The diagnosis can be confirmed with molecular genetic testing, which involves sampling from a cheek swab to determine the presence and activity of RPS6KA3 and RSK2. This varies slightly between the sexes, and, notably, such tests can only confirm a suspected diagnosis. A small percentage of those with the condition have no detectable mutation.  

Treatment

There’s no single, standard treatment for this condition; rather, approaches to Coffin-Lowry syndrome are based on the type and severity of symptoms. Those with the condition should have their cardiac health, hearing, and vision tested regularly.

In addition, anti-epileptic drugs may be prescribed for stimulus-induced drop episodes, and those experiencing these symptoms may need to wear helmets. Furthermore, physical therapy or even surgery may be necessary to treat the spinal curvature associated with the condition, as this can eventually impact respiratory capacity and cardiac health.

To take on the intellectual and developmental aspects of this condition, physical and occupational therapy approaches—alongside specially catered education—can also be very helpful. Furthermore, genetic counseling—in which a doctor talks to a family about the risk of inheriting congenital conditions like this—is often recommended.

Coping

There’s no doubt that a condition with such a cascade of effects leaves a heavy burden. Depending on the severity of the Coffin-Lowry syndrome case, treatment may become an ongoing and intense process. Family members of those affected will need to play an important supportive and empathetic role. That said, with the right support and intervention, people with the condition can achieve a fine quality-of-life. Therapy and support groups may also be beneficial for families of those living with the syndrome.

A Word From Verywell

Coffins-Lowry syndrome is difficult because there’s no singular, established cure for it. The primary approaches, as noted above, involve managing effects and symptoms, which requires care and dedication. Taking it on means being proactive and engaged; it means arming yourself and your loved ones with knowledge, and it means finding the right kind of medical help. Part and parcel with that is a willingness to be communicative and clear with caregivers, family, and those with condition alike.

The good news is that understanding of this syndrome—as well as all congenital diseases—is growing rapidly, and treatment options are expanding. The fact of the matter is that today we are better than ever equipped to confront Coffin-Lowry syndrome cases. And with every advance, the outlook grows brighter and brighter.   

Was this page helpful?

Article Sources

  1. National Institutes of Health. Coffin-Lowry syndrome. Genetics Home Reference. Published 2016. 


  2. National Organization for Rare Disorders. Coffin Lowry Syndrome. Published 2018. 


  3. Rogers R, Abidi F. Coffin-Lowry syndrome - Conditions. Published 2018. 


Additional Reading