An Overview of Coffin Lowry Syndrome

Coffin Lowry is a rare genetic disorder that has a variety of signs and symptoms, including facial and skeletal abnormalities, mental retardation, low muscle tone and short stature. The disorder is equally distributed in males and females, but generally are more severe in males. It is thought that as many as 1 in 40,000 to 50,000 are affected by this syndrome.

A mutation in the gene, RPS6KA3, on the X chromosome seems to cause Coffin Lowry syndrome. However, it is still unclear as to what causes the mutation in this gene and what preventative actions could be taken to avoid this syndrome.

Facial features in affected individuals can include:

• An underdeveloped upper jaw bone
• Wide spaced eyes
• Large nose
• A prominent brow
• Low set ears
• Thick eyebrow
• Slanted eyelids

Skeletal characteristics are:

• Curvature of the spine
• Tapered, short fingers
• Exaggerated breastbone
• Dental irregularities

Organ complications include:

• Hearing impairment
• Respiratory aliments
• Muscular movement irregularities; gait
• Heart and kidney complications

As an X-linked dominant trait, Coffin Lowry syndrome is caused by a mutation on the gene RPS6KA3 which encodes a protein RSK2. Males often experience more severe complications of the disorder than do females. Men who inherit the affected X chromosome will be affected, whereas females will be carriers and at risk of developmental delays and other mild symptoms of Coffin Lowry syndrome. As it is not yet understood what causes this mutation, there are no preventative actions that are known to diminish the inheritance of this gene.

RSK2 is known to be involved in cell signaling and pathways. When inhibited, researchers believe that the development of the central nervous system is decreased due to the lack of signaling between cells.

There are known patients with Coffin Lowry that do not exhibit the mutation of RPS6KA3 and therefore the etiology is unknown.

Currently, there is no cure or long-term course of action for the complete treatment of the genetic disorder Coffin Lowry syndrome. However, treatment options do exist to help or treat speech and hearing impairments, mental retardation and therapies for muscular movement. Most therapies are available from schools and community centers, outpatient clinics, hospitals and other various rehabilitation centers.

Coffin Lowry syndrome can be determined by undergoing a complete sequence test of the X chromosome from the patient in question. The test reveals the bases of the gene and when known, can determine if the chromosome is mutated or not. Testing will usually require a meeting with a genetic counselor that will assess the family history, the patient in question, and even review options; such as testing, possible courses of treatment and more.

• http://ghr.nlm.nih.gov/condition/coffin-lowry-syndrome
• http://www.ninds.nih.gov/disorders/coffin_lowry/coffin_lowry.htm
• http://www.nature.com/ejhg/journal/v18/n6/full/ejhg2009189a.html