Coffin-Lowry syndrome

Coffin-Lowry syndrome (CLS) is a rare genetic disorder caused by loss-of-function mutations in the RPS6KA3 gene (also known as RSK2), located on the X chromosome. This gene encodes a serine/threonine kinase involved in cell signaling pathways critical for learning, memory, and skeletal development. The condition predominantly affects males, who typically present with the full spectrum of clinical features, while heterozygous females may show variable manifestations ranging from unaffected to moderately affected. Key clinical features include moderate to severe intellectual disability in affected males, characteristic facial features (prominent brow ridge, wide nasal bridge, thick nasal septum, anteverted nares, thick everted lips, and widely spaced teeth), and progressive skeletal abnormalities such as kyphoscoliosis, pectus carinatum or excavatum, and short, broad, tapering fingers with soft and fleshy hands. Growth retardation leading to short stature is common. A distinctive feature seen in some patients is stimulus-induced drop episodes (SIDAs), which are sudden episodes of collapse triggered by unexpected tactile or auditory stimuli, without loss of consciousness. These episodes typically begin in childhood or adolescence. Additional features may include sensorineural hearing loss, cardiac abnormalities (including mitral valve prolapse), and microcephaly. There is no cure for Coffin-Lowry syndrome, and management is supportive and symptomatic. Treatment may include special education programs, speech therapy, physical therapy, and orthopedic interventions for skeletal complications. Anticonvulsant medications such as clonazepam or valproate may help manage stimulus-induced drop episodes. Regular cardiac and audiological monitoring is recommended. Genetic counseling is important for affected families.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

Common questions about Coffin-Lowry syndrome