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A male infant is born with severe hydrocephalus requiring shunting. He has adducted thumbs and later develops spastic paraplegia. Family history is notable for 2 affected maternal uncles with similar symptoms.

XLR; L1CAM gene

  • Hydrocephalus (aqueductal stenosis) → extra "L1quid" in the brain
  • "L1": Leg spasticity + 1ntellectual disability
  • Adducted (clasped) thumbs (affects "1st" digit)
  • Spastic paraplegia (MASA syndrome = milder variant)
  • Agenesis of corpus callosum
  • Suspect in males with congenital hydrocephalus (aqueductal stenosis), adducted thumbs, and spasticity, especially with an X-linked family history
  • Brain MRI: aqueductal stenosis, hydrocephalus, and corpus callosum hypoplasia/agenesis
  • Confirm with molecular testing of L1CAM; spectrum spans L1 syndrome and the milder MASA phenotype
  • Carrier testing of at-risk female relatives and prenatal/preimplantation testing once the familial variant is known
  • Neurosurgical CSF shunting for symptomatic hydrocephalus
  • Multidisciplinary supportive care: physical/occupational therapy and spasticity management (orthotics, baclofen, botulinum toxin)
  • Developmental and educational support for intellectual disability
  • Genetic counseling for X-linked recessive inheritance (carrier mothers, 50% risk to sons)

Mnemonic: Hydrocephalus
"X-L1nked recessive": The "1" in L1 reminds you of the X-linked recessive inheritance of L1CAM.

"L1quid in the brain": Hydrocephalus (extra "L1quid") causes macrocephaly.

"1st digit": Adducted (clasped) thumbs affect the "1st" digit.

"Leg spasticity, 1ntellectual disability": The "L" and "1" in L1 represent the two key neurological features.

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