Segmental overgrowth disorders - Deep sequencing

Gene: PIK3CA

Comment on mode of inheritance: Changed MOI from 'Other' to 'monoallelic' following discussion with clinical team.

Created: 11 Apr 2017, 1:32 p.m.

In a number of patients with CLOVE syndrome (OMIM:612918), Kurek et al., 2012 (PMID:22658544) identified somatic mosaic mutations in the PIK3CA gene (H1047R rs121913279, E542K rs121913273, C420R rs121913272 mutations) in affected tissues. They concluded that CLOVE syndrome is caused by postzygotic activating mutations in PIK3CA. Full details are available on OMIM.

In a number of patients with MCAP (OMIM:602501), mosaic mutations have been found (G914R rs587776932, C378Y rs397514565, H1047Y rs121913281); the C378Y mutation shows varying levels of mosaicsm. Full details are available on OMIM.

Created: 15 Nov 2016, 4:50 p.m.

Comment on list classification: Updated rating from Amber to Green because PIK3CA in original list provided by Richard Scott.

Created: 7 Nov 2016, 2:47 p.m.

CLOVE syndrome can be caused by somatic mosaicism for postzygotic activating mutations in the PIK3CA gene.

Created: 7 Nov 2016, 2:41 p.m.

Mode of inheritance
Other

Mode of pathogenicity
Other

Green List (high evidence)

Phenotypes
Megalencephaly-capillary malformation-polymicrogyria syndrome, 602501; MCAP; congenital lipomatous overgrowth, vascular malformations, and epidermal nevi, 612918; CLOVE syndrome; Macrocephaly and Overgrowth Syndromes; Megalencephaly-Capillary malformation syndrome; Congenital Lipomatous Overgrowth Vascular Malformations, Epidermal Nevi and Scoliosis/Skeletal/Spinal anomalies syndrome; CLOVES syndrome; Congenital Lipomatous Overgrowth, Vascular Malformations, and Epidermal Nevi; Megalencephaly-Capillary Malformation- Polymicrogyria Syndrome; CLOVES; Megalencephaly-capillary malformation-polymicrogyria syndrome, somatic; macrocephaly-capillary malformation (MCM) syndrome