The megalencephaly-polymicrogyria-polydactyly-hydrocephalus (MPPH) syndrome is characterized by:

  • Megalencephaly (MEG) – often congenital
  • Polymicrogyria
  • Hydrocephalus – may require neurosurgical intervention
  • Polydactyly – typically postaxial polydactyly

Mutations are most often heterozygous de novo. Mosaic mutations have also been reported.

Focal brain malformations including hemimegalencephaly (HMEG) and focal cortical dysplasia (FCD) are characterized by early onset, often intractable, epilepsy.
Mutations are most often post-zygotic (mosaic).

Diffuse megalencephaly (MEG) with polymicrogyria (similar to MCAP syndrome) is associated with:

  • Epilepsy
  • Oromotor dysfunction (expressive speech delay, difficulties handling oral secretions, dysphagia)

Mutations are most often heterozygous de novo, or rarely post-zygotic (mosaic).

Diffuse megalencephaly without cortical dysplasia is associated with:

  • Intellectual disability
  • Autism spectrum disorders
  • Behavioural issues

Mutations are most often heterozygous de novo or rarely post-zygotic (mosaic).