Coffin-Lowry syndrome
Coffin-Lowry syndrome is a genetic condition characterized by intellectual disability, distinctive facial features, and skeletal abnormalities, with symptoms typically more severe in males.
Overview
Coffin-Lowry syndrome affects many parts of the body. While symptoms range from mild to severe in females, males typically experience severe to profound intellectual disability and delayed development.
Symptoms
Features of the syndrome often become more pronounced with age and include:
- Stimulus-induced drop episodes (SIDEs): Beginning in childhood or adolescence, some individuals experience brief episodes of collapse when excited or startled by loud noises.
- Facial features: A prominent forehead, widely spaced and downward-slanting eyes, a short nose with a wide tip, and a wide mouth with full lips.
- Skeletal and physical traits: Soft hands with tapered fingers, short stature, an unusually small head (microcephaly), and progressive abnormal curvature of the spine (kyphoscoliosis).
Causes
The condition is caused by mutations in the RPS6KA3 gene. This gene provides instructions for making a protein involved in cell signaling, which is crucial for brain function, including learning, long-term memory formation, and nerve cell survival. Mutations result in little or no production of this protein, though the exact mechanism linking this deficiency to the syndrome's symptoms is not fully understood.
Inheritance
Coffin-Lowry syndrome is inherited in an X-linked dominant pattern. Because the gene is located on the X chromosome, males (who have one X chromosome) are generally more severely affected than females (who have two). Fathers cannot pass X-linked traits to their sons.
Approximately 70 to 80 percent of cases are caused by new mutations in the RPS6KA3 gene with no family history of the condition. The remaining 20 to 30 percent of individuals have other family members affected by the syndrome.