Surgical management of Chiari malformation type 1 associated to MCAP syndrome and study of cerebellar and adjacent tissues for PIK3CA mosaicism

Eur J Med Genet. 2023 Feb;66(2):104678. doi: 10.1016/j.ejmg.2022.104678. Epub 2022 Dec 9.


Background: Subjects with Megalencephaly-Capillary Malformation-Polymicrogyria syndrome (MCAP) can present with a Chiari Malformation Type 1 and resulting alterations in cerebrospinal fluid (CSF) dynamics, which may require surgical treatment. The aim of this paper is to describe the features of children with MCAP who underwent surgical decompression for CM1, and to explore the PIK3CA variant allele frequency (VAF) identified in cerebellar parenchyma and other adjacent structures.

Methods: This study reviewed two cases of children with CM1 and MCAP who underwent surgical decompression treatment. These two cases were part of a national cohort of 12 MCAP patients who had CM1, due to their surgical eligibility. Tissue samples were obtained from the cerebellar tonsils and adjacent anatomical structures during the surgical procedures. Samples were then subsequently analyzed for PIK3CA postzygotic variants.

Results: In both cases, alterations in CSF dynamics, specifically hydrocephalus and syringomyelia, were observed and required surgical treatment. PIK3CA targeted sequencing determined the VAF of the postzygotic variant in both cerebellar and adjacent bone/connective tissues.

Discussion: The recognition of a CM1 comorbidity in MCAP patients is of paramount importance when considering personalized treatment options, especially because these patients are at higher risk of developing complications during surgical decompression surgery. The variable PIK3CA VAF identified in the different analyzed tissues might help explain the heterogeneous nature and severity of anomalies observed in the volume of the posterior fossa structures in MCAP patients and associated CSF and venous disorders.

Keywords: Cerebellar ectopia; Cerebrospinal fluid; Hydrocephalus; MCAP; PIK3CA; Physiopathology; Suboccipital decompression; Syringomyelia.

MeSH terms

  • Arnold-Chiari Malformation* / complications
  • Arnold-Chiari Malformation* / genetics
  • Arnold-Chiari Malformation* / surgery
  • Child
  • Class I Phosphatidylinositol 3-Kinases / genetics
  • Humans
  • Megalencephaly* / complications
  • Mosaicism
  • Treatment Outcome


  • Class I Phosphatidylinositol 3-Kinases
  • PIK3CA protein, human

Supplementary concepts

  • Megalencephaly cutis marmorata telangiectatica congenita