Plastic Surgery Research Council
Members Only  |  Contact  | 
PSRC on Facebook  PSRC on Twitter

Back to Annual Meeting Program

Presenter: Reid Maclellan, MD
Co-Authors: Greene AK; Luks VL; Mulliken JB; Warman ML; Kurek KC
Boston Childrens Hospital Harvard Medical School

Background: Facial infiltrating lipomatosis (FIL) is a rare, congenital, non-heritable, disorder characterized by hemifacial soft-tissue and skeletal overgrowth, precocious dental development, macrodontia, hemimacroglossia, and mucosal neuromas. It has been hypothesized that FIL is caused by a somatic mutation, with regional expression, that arose during embryonic development. The purpose of this study was to search for causative somatic mutations in patients with FIL by using massively parallel sequencing.

Methods: Human FIL tissue was obtained prospectively from 4 patients during a clinically-indicated procedure and stored frozen. DNA was extracted from these specimens to produce massively parallel sequencing libraries that were enriched for coding sequences from genes involved in pathways that control cell growth using targeted capture. We massively parallel sequenced the enriched libraries and analyzed the sequence data for mutations that appeared to be mosaic and unique to the affected tissue.

Results: We identified a different missense mutation in PIK3CA in each patient s affected tissue. PIK3CA encodes the catalytic subunit of the enzyme phosphoinositide-3-kinase (PI3K), which promotes cell growth. One patient had a nucleotide transition that changed a histidine to an arginine codon at the amino acid residue 1047 (p.H1047R), the other patients had different amino acid mutations: p.H1047L, p.E453K, or p.E542K. Each mutation is predicted to significantly increase enzymatic activity. The frequency of mutant cells in the affected tissue ranged from 12% to 68%, compatible with their representing somatic mosaic rather than germline mutations.

Conclusions: Somatic mosaic mutations in PIK3CA cause FIL. Interestingly, similar mosaic mutations have recently been identified in patients with other overgrowth disorders including CLOVES syndrome, hemimegalencephaly, and segmental fibroadipose hyperplasia. PIK3CA inhibitors are currently in clinical trials for cancers containing PIK3CA mutations; they may be efficacious in patients with FIL and other PIK3CA-associated overgrowth syndromes.

Back to Annual Meeting Program