SG06 (P061) Blaschko linear hypopigmentation caused by <i>GNA11</i> and <i>PIK3CA</i> mosaicism

Abstract Blaschko linear hypopigmentation has been attributed to multiple mosaic genetic causes including chromosomal abnormalities and single gene variants. However, many cases remain unsolved. Two unrelated female children presented to our service for assessment of abnormal pigmentation. The first, aged 2 years, had extensive Blaschko linear hypopigmentation on the left upper limb, left trunk and left lower limb but no other symptoms or signs. The second, aged 12 years, had Blaschko linear hypopigmentation affecting the left lower limb, in addition to four café au lait macules and a small capillary malformation under the left lower eyelid, but no other symptoms or signs. Both patients were consented for genetic testing and a skin biopsy was taken from a representative area of hypopigmentation. DNA was extracted directly from the whole biopsy and underwent targeted next-generation sequencing. Patient 1 was found to have a pathogenic variant in GNA11 c.547C&amp;gt;T p.(Arg183Cys) at 1.5% variant allele frequency. Patient 2 was found to have a pathogenic variant in PIK3CA c.1633G&amp;gt;A p.(Glu545Lys) at 4% variant allele frequency. Neither GNA11 nor PIK3CA has been described previously to cause Blaschko linear hypopigmentation. However, the exact variants described here are well known in the context of other cutaneous mosaic diseases. The mosaic GNA11 variant can cause port-wine stains with or without Sturge–Weber syndrome, phakomatosis pigmentovascularis with dermal melanocytosis, and extensive dermal melanocytosis. The mosaic PIK3CA variant can cause overgrowth, vascular or lymphatic malformations and epidermal naevi. This is therefore highly supportive of the pathogenicity of these variants in this new clinical presentation. As Blaschko linear patterning is a sign of genetic disease affecting the epidermal lineage, we propose that this new phenotype is caused by the mosaic variant affecting that lineage. These cases expand our current knowledge of mosaic variants causing Blaschko linear hypopigmentation, and of the disease phenotypes caused by mosaicism for GNA11 and PIK3CA. GNA11 and PIK3CA testing should be considered in children presenting with Blaschko linear hypopigmentation.