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Case Reports
. 2020 Sep 12:2020:8826945.
doi: 10.1155/2020/8826945. eCollection 2020.

Gingival Biopsy to Detect Mosaicism in Overgrowth Syndromes: Report of Two Cases of Megalencephaly-Capillary Malformation Syndrome with Periodontal Anomalies

Mathieu Marty  1 , Carole Bonnaud  1 , Natalie Jones  2 , Michel Longy  2 , Frédéric Vaysse  1 , Eric Bieth  3 , Isabelle Bailleul-Forestier  1   4
Affiliations
Case Reports

Gingival Biopsy to Detect Mosaicism in Overgrowth Syndromes: Report of Two Cases of Megalencephaly-Capillary Malformation Syndrome with Periodontal Anomalies

Mathieu Marty et al. Case Rep Dent. .

Abstract

Background: Megalencephaly-capillary malformation (MCAP) is a rare overgrowth syndrome caused by postzygotic activating mutations in the PIK3CA gene.

Aim: To illustrate the benefits of gingival biopsy in the genetic diagnosis of overgrowth syndromes.

Design: Gingival biopsy was performed on a 13-year-old patient and a 16-year-old patient with MCAP and who suffered from periodontal disease. PIK3CA sequencing was performed on DNA extracted from gingival biopsies, blood, and saliva.

Results: Pathogenic p.Glu365Lys and p.Glu545Asp PIK3CA mutations were found in the gingival biopsies with an allelic frequency of 22% and 35%, respectively, while they were undetectable in blood or saliva. The genetic diagnosis of MCAP through detection of PIK3CA somatic mosaicism in a periodontal biopsy is unprecedented.

Conclusions: Considering the tissue distribution and level of somatic mosaicism for PIK3CA mutation, the composite embryologic origin of periodontium and its high fibroblast cell content make it an ideal target for molecular analysis in overgrowth syndromes, and multidisciplinary approach including paediatric dentists should be encouraged. In addition, our clinical findings suggest that periodontal disease is part of the MCAP phenotypic spectrum and should be systematically investigated.

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Conflict of interest statement

None of the authors had conflicts of interest to declare.

Figures

Figure 1
Figure 1
(a) Intraoral initial situation. (b) Intraoral situation after root planning and gingivectomy. (c) At 6 months, end of the first phase of periodontal treatment.
Figure 2
Figure 2
Identification of a mosaic PIK3CA missense mutation in a gingival biopsy. (a) Next-generation sequencing (NGS) of the gingival biopsy sample identified a missense mutation in exon 6 of the PIK3CA gene, as indicated by the yellow square. Twenty-two percent of reads showed the G>A change (324/1475 reads, 174+ 150-), suggesting a potential mosaic mutation. (b) Direct Sanger sequencing of 3 independent samples from the patient confirmed the presence of the missense mutation in the (i) gingival biopsy sample and showed the absence of this mutation in the (ii) blood and (iii) saliva samples, supporting the hypothesis of a mosaic mutation.
Figure 3
Figure 3
(a) Intraoral situation for patient 2. (b) Aspect of the inflammatory papillae between teeth 42 and 43. (c) Result of the genetic analysis.
See this image and copyright information in PMC

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