P126 A novel phenotype of eruptive pyogenic granulomas and bone involvement due to mosaic <i>NRAS</i> mutations

Abstract Somatic overgrowth syndromes include a spectrum of disorders, ranging from those predominantly characterized by vascular malformations to those with significant tissue overgrowth and minimal vascular involvement. These conditions arise from pathogenic somatic mosaic mutations, resulting in a diverse array of clinical and pathological manifestations. We present a case series of NRAS mosaic mutations presenting with specific clinical features. Case 1 is a 13-year-old boy who presented with a painful vascular anomaly of the left femur and a colocalized capillary malformation (CM), which subsequently developed recurrent pyogenic granuloma (PG)-like lesions. Bone histopathology showed a vascular lesion, which was positive for NRAS. Excisional biopsy of the PG-like lesion was consistent with a PG and also showed the same pathogenic NRAS mutation. Case 2 is a 16-year-old girl who was noted to have a large CM of the right leg with hypertrophy and increased limb length. An NRAS mutation was detected in a skin biopsy. Case 3 is a 20-year-old man who has recurrent PG of the right arm and shoulder area with a confirmed mosaic mutation in NRAS. Case 4 is an 11-year-old boy with multiple PGs on the right side of his back with a causative mosaic NRAS mutation. Case 5 is an 18-year-old man with a similar phenotype characterized by PG of the right shoulder area caused by a mosaic NRAS mutation. Case 6 is a 54-year-old woman with a progressive venous malformation of the head and neck, with painful depressed osseous abnormalities of the skull associated with digenic mosaicism in NRAS and TEK. Although her clinical phenotype is largely in keeping with a TEK mutation, the bony lesions may be related to the NRAS mutation, similarly to case 1. We present case series of a mosaic NRAS mutations leading to vascular malformations involving skin. The majority of our patient cohort (cases 1, 3, 4 and 5) exhibited PG-like lesions with or without a CM in the affected area. Vascular malformations with mutations in NRAS are uncommon entities. In addition to providing a genetic diagnosis, genetic analysis also provides potential targeted treatment options, highlighting the possibility of targeting the RAS–RAF–MAPK–ERK pathway. In conclusion, this new genotype–phenotype correlation may aid in future diagnosis and can also provide direction for targeted therapy for these patients.