Coffin-Lowry syndrome

December 31, 2014

Overview

Coffin-lowry syndrome was characterised by Coffin (1966) and Lowry (1971). Coffin-Lowry syndrome was independently described by Dr. Coffin and his associates in 1966 and later described by Dr. Lowry and associates in 1971. Dr. Temtamy showed that the cases represented a single syndrome in 1975

Symptoms

Coffin-Lowry syndrome is a severe mental retardation associated with abnormalities of: Growth In utero growth is normal but post natal growth is retarded. Patients are sometimes microcephalic. Cardio-vascular Cardiac abnormalities affect 15% of the patients. Skeleton Progressive kyphoscoliosis affects 1 in 2 patients. Vision and audition Auditory abnormalities are frequent and often present. Vision abnormalities are not often present.

Causes

Mutations in the RPS6KA3 gene cause Coffin-Lowry syndrome.[4] This gene is located on the short arm of the X chromosome (Xp22.2). The RPS6KA3 gene makes a protein that is involved with signaling within cells. The protein RSK2 which is encoded by the RPS6KA3 gene is a kinase which phosphorylates some substrates like CREB and histone H3. RSK2 is involved at the distal end of the Ras/MAPK signaling pathway. Researchers believe that the protein helps control the activity of other genes and may play an important role in the central nervous system. Mutations in the RPS6KA3 disturb the function of the protein, but it is not well understood how mutations lead to the signs and symptoms of Coffin-Lowry syndrome. At this time more than 120 mutations have been found1. Some people with the features of Coffin-Lowry syndrome do not have identified mutations in the RPS6KA3 gene. In these cases, the cause is unknown. This condition is inherited in an X-linked dominant pattern. A condition is considered X-linked if the gene that causes the disorder is located on the X chromosome (one of the two sex chromosomes). The inheritance is dominant if one copy of the altered gene is sufficient to cause the condition. In most cases, males experience more severe symptoms of the disorder than females. A striking characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.

Prognosis

There is no cure and no standard course of treatment for Coffin-Lowry syndrome. Treatment is symptomatic and supportive, and may include physical and speech therapy and educational services.