Neurosurgery notes/CSF/Hydrocephalus (HCP)/X-linked hydrocephalus

X-linked hydrocephalus

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Hydrocephalus (HCP)

General information

  • Inherited hydrocephalus (HCP) with phenotypic expression in males, passed on through carrier mothers who are phenotypically normal.
  • Classical phenotypic expression will skip single generations.

Numbers

  • Incidence: 1/25,000 to 1/60,000.
  • Prevalence: ≈ 2 cases per 100 cases of hydrocephalus.

Genetics

  • X-linked pattern
  • Mutations in the L1CAM gene (Xq28) encoding the L1 cell adhesion molecule that is expressed mainly in the developing nervous system.
  • L1CAM membrane-bound receptor
    • Function
      • CNS development for axonal migration to appropriate target locations through Integrin cell adhesion molecules and MAP Kinase signal cascade.

Pathophysiology

  • Abnormal gene expression results in poor differentiation and maturation of cortical neurons, macroscopic anatomical abnormalities.
  • Mild L1 Syndrome
    • Mutations retaining expression of some functional protein (component imbedded in cell membrane)
    • Adducted thumbs, spastic paralysis, hypoplasia of CC
  • Severe L1 syndrome
    • Cytoplasmic domain loss of function mutations
    • Symptoms of mild L1 syndrome
    • Anterior cerebellar vermis hypoplasia
    • Large massa intermedia, enlarged quadrigeminal plate, rippled ventricular wall following VP shunt placement (pathognomonic for X-linked HCP).
    • Profound mental retardation in virtually all cases

L1 syndromes

  • Classical syndromes
    • CRASH
      • Corpus callosum hypoplasia
      • Retardation
      • Adducted thumbs (clasp thumbs)
      • Spastic paralysis
      • HCP
    • MASA
      • Mental handicap
      • Aphasia
      • Shuffling gait
      • Adducted thumbs
    • HSAS
      • HCP with Stenosis of the Aqueduct of Sylvius.
  • Recent delineations
    • Mild L1 syndrome
      • Adducted thumbs, spastic paralysis, hypoplasia of CC
    • Severe L1 syndrome

Radiographic findings

  • (Esp for severe cases)
    • Severe symmetric HCP with predominant posterior horn dilation
    • Hypoplastic CC/ACC
    • Hypoplastic anterior cerebellar vermis
    • Large massa intermedia
    • Large quadrigeminal plate
    • Rippled ventricular wall following VP shunt placement (pathognomonic)
notion image

Treatment

  • No intervention demonstrates improvement in retardation status in observational papers.
  • VP shunt
    • Main purpose is management of head size for improved care by caregiver.
    • Does not improve neurologic outcome
  • No genetic therapies for L1CAM protein abnormalities
  • Prenatal U/S
    • Early (≈ 20–24 weeks gestational age) with frequent repeat scan in known carrier mothers.
    • May allow for medically indicated termination early on.
  • Genetic testing for L1CAM mutation
    • Male infants with HCP and≥ 2 clinical/radiographic signs