Within our cells, intricate communication networks direct fundamental life processes. A component of this system is the enzyme Ribosomal S6 Kinase 2 (RSK2). This protein kinase functions as a cellular messenger, relaying signals that influence activities necessary for health. The instructions for building RSK2 are provided by the RPS6KA3 gene.
The Role of RSK2 in Cellular Processes
The RSK2 protein operates within a signaling network called the MAPK/ERK pathway. This pathway acts as a command chain inside the cell, responding to external cues and translating them into specific actions. RSK2 receives signals from another protein, ERK, and carries the message forward by activating other molecules to trigger a cellular response.
Through its position in this pathway, RSK2 regulates cell growth, proliferation, and survival. By phosphorylating numerous targets, it helps control the expression of genes and the synthesis of proteins for these activities. RSK2 helps interpret signals that tell a cell when to divide, grow, and stay alive.
The protein’s influence extends to the nervous system, as it is prominently expressed in brain regions associated with learning and memory. Its activity in neurons is connected to synaptic plasticity, which is the ability of connections between nerve cells to strengthen or weaken over time. This adaptability is a fundamental mechanism for how memories are formed.
Coffin-Lowry Syndrome
Mutations in the RPS6KA3 gene cause a deficient or non-functional RSK2 protein, leading to a rare genetic disorder called Coffin-Lowry syndrome (CLS). This loss of RSK2 function disrupts normal cell signaling, causing the developmental and physical traits associated with the condition. The incidence of CLS is estimated to be between 1 in 50,000 and 1 in 100,000 people.
Individuals with CLS often present with a recognizable set of physical characteristics, which may progress in severity over time. These include:
- A prominent forehead, wide-set eyes, a flattened nasal bridge, and a wide mouth with full lips
- Broad, soft hands with short, tapered fingers
- Short stature
- Skeletal changes like a forward curvature of the spine (kyphosis) or a sideways curvature (scoliosis)
Beyond physical traits, Coffin-Lowry syndrome involves developmental challenges. Cognitive impairment is a feature, with intellectual disability ranging from moderate to severe. Sensorineural hearing loss and cardiac issues, such as mitral valve dysfunction, can also be associated with the syndrome. The presentation of CLS is highly variable, and symptoms can differ greatly from person to person.
Genetic Basis and Inheritance
Coffin-Lowry syndrome is caused by mutations in the RPS6KA3 gene, which is located on the X chromosome. Due to this location, the disorder follows an X-linked inheritance pattern, which has different implications for males (XY) and females (XX).
A male who inherits a mutated RPS6KA3 gene on his single X chromosome will develop Coffin-Lowry syndrome. He will experience the full range of symptoms with greater severity because he lacks a second, normal copy of the gene to produce functional RSK2 protein.
Females who inherit the mutated gene are often less severely affected because their second X chromosome has a normal copy of the RPS6KA3 gene. This allows their bodies to produce some functional RSK2, resulting in presentations ranging from asymptomatic to having mild features. The mutation can be inherited from a carrier mother or occur as a new (de novo) mutation.
Diagnosis and Management
While clinical findings and physical characteristics can suggest a diagnosis, molecular genetic testing provides confirmation. This process involves sequencing the RPS6KA3 gene to identify one of the more than 140 pathogenic mutations known to cause the disorder.
There is no cure for Coffin-Lowry syndrome, so management is a supportive, multidisciplinary approach tailored to an individual’s needs. This strategy aims to manage symptoms and maximize functional abilities. A team of specialists collaborates to create a comprehensive care plan.
This plan often includes physical therapy to address motor skills, occupational therapy for daily living activities, and speech therapy for communication challenges. Individualized educational plans are put in place to support learning. Regular surveillance for potential health complications, like cardiac and skeletal issues, is also a standard part of long-term care.