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Coffin-Lowry syndrome

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A teenage boy has severe intellectual disability, coarse facial features with a prominent forehead and widely spaced eyes, and large soft hands with tapered fingers.

XLD; RPS6KA3 gene

  • Intellectual disability (severe in males, variable in females)
  • Coarse facies, prominent forehead, hypertelorism
  • Large, soft hands with tapered fingers
  • Skeletal abnormalities, progressive kyphoscoliosis
  • Stimulus-induced drop attacks (some patients)
  • Clinical recognition: characteristic coarse facies, large soft hands with tapered fingers, and intellectual disability (severe in males)
  • Confirm with molecular testing of RPS6KA3 (sequencing plus deletion/duplication analysis); females show variable expression
  • Skeletal survey for vertebral and hand changes (drumstick terminal phalanges); echocardiogram for valvular disease
  • Multidisciplinary developmental, educational, speech, and physical/occupational therapy
  • Orthopedic monitoring for progressive kyphoscoliosis; cardiology surveillance for mitral valve disease and arrhythmia
  • For stimulus-induced drop attacks, protective measures (wheelchair/helmet) and trial of medications (e.g., clonazepam or selective serotonin reuptake inhibitors); periodic hearing screening

"There's a coRPSe in the Coffin": The gene is RPS6KA3 (Ribosomal Protein S6 Kinase A3).

"Seeing a Coffin will make you fall Low": Stimulus-induced drop attacks (SIDAs), brief collapse after unexpected stimulus. "CoLlapse in Coffin-Lowry."

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