Neuropediatrics 2015; 46 - FV03-05
DOI: 10.1055/s-0035-1550665

Somatic PIK3CA Mosaic as a Cause of Hemimegalencephaly and Congenital Infiltrating Lipomatosis of the Face

A. Hahn 1, J. Hoffmann 2, S. Biskup 2, B. Reich 3, I. Scheer 4, K. Mayer 4, B. Neubauer 5
  • 1Abteilung Neuropädiatrie, Gießen, Germany
  • 2Center for Genomics and Transcriptomics, Tübingen, Germany
  • 3Kinderherzentrum, Gießen, Germany
  • 4Abteilung Neuroradiologie, Zürich, Switzerland
  • 5Abteilung Kinderneurologie, Gießen, Germany

Case Study: Hemimegalencephaly (HME) is a rare malformation of cortical development characterized by enlargement of one cerebral hemisphere associated with focal or diffuse neuronal heterotopia. Congenital infiltrating lipomatosis of the face (CILF) is defined as progressive hemifacial soft-tissue and skeletal overgrowth present from birth. The combination of HME and CILF (HME–CILF) has been rarely reported as a distinct clinical entity of unknown pathogenesis.

Recently, gain of function mutations in different components of the PI3K-AKT3-mTOR pathway have been identified in brain tissues from some individuals with HME, and mutations in PIK3CA, encoding the α subunit of the enzyme phosphoinositide-3-kinase, have been detected in affected tissues from all subjects with isolated CILF investigated.

Therefore, we performed deep sequencing of the PIK3CA gene in DNA extracted from affected tissue obtained by an intraoral biopsy and from the blood of a 3-month-old boy presenting with HME–CILF.

This detected the mutation c.1258T > C (p.C420R) at a frequency of 26% in the biopsy sample. As this mutation was not present in the patient's blood, this suggests a somatic mosaic, eventually arisen in the neural crest cell component of primitive ectoderm during early embryogenesis, as the cause of the patients' symptoms.

These findings demonstrate that overgrowth in HME–CILF can be secondary to overactivation of the PI3K-AKT3-mTOR pathway, adds HME–CILF to the list of disorders caused by germ line or somatic mutations in PIK3CA, and suggests that deep sequencing of PIK3CA in affected tissue obtained by biopsy is an effective and minimally invasive method to identify the genetic defect. Early identification of the underlying mutation may be of clinical relevance, because inhibition of PI3K-AKT3-mTOR pathway activity is principally feasible.

Keywords: hemimegalencephaly, congenital infiltrative lipomatosis of the face, PIK3CA.