Coffin-Lowry syndrome

Coffin-Lowry syndrome is an X-linked dominant genetic disorder that causes intellectual disability, often together with abnormalities of growth, cardiac abnormalities, kyphoscoliosis, and auditory and visual problems. It arises from mutations in the RPS6KA3 gene on the X chromosome, which produces the RSK2 protein needed for cell signaling pathways involved in learning, memory formation, and nerve cell survival. Over 120 distinct mutations have been identified, though a minority of patients with the clinical picture have no detectable mutation. Males are typically affected more severely than female carriers. Common features include cognitive disability of varying severity, muscular spasticity, progressive muscle weakness that can lead to paralysis, distinctive facial characteristics such as a flattened nose, widely spaced downward sloping eyes, a prominent forehead and large lips, small tapered fingers, hearing loss, and abnormal spine curvature. Affected individuals face an elevated stroke risk and some experience stimulus induced drop attacks, sudden temporary paralysis triggered by unexpected sensory stimuli. Grange S. Coffin first described the condition in 1966, Robert Brian Lowry independently identified it in 1971, and it was established as a single syndrome in 1975; the responsible RSK2 gene was identified in 2002.