Gene/phenotype/disorder of interest
- Epidermal Nevus Syndromes (ENS) — HRAS, KRAS, NRAS (ORPHA: 35125)
- Schimmelpenning-Feuerstein-Mims Syndrome (SFMS) — HRAS, NRAS, KRAS (OMIM #163200; ORPHA: 35122)
- Cutaneous Skeletal Hypophosphatemia Syndrome (CSHS) — HRAS, NRAS (OMIM #659000; ORPHA: 563996)
- Keratinocytic Epidermal Nevus Syndrome (KENS) — KRAS (OMIM #162900; ORPHA: 476)
- Phacomatosis Pigmentokeratotica (PPK) — HRAS, KRAS, BRAF, FGFR1 (OMIM #174710; ORPHA: 2874)
- Encephalocraniocutaneous Lipomatosis (ECCL) — KRAS, NRAS (OMIM #613001; ORPHA: 2396)
- Oculo-Ectodermal Syndrome (OES) — KRAS (OMIM #600268; ORPHA: 2717)
- Gorham-Stout Disease — KRAS (OMIM #123880; ORPHA: 73)
- Mosaic Lymphatic Anomalies — SOS1, KRAS, ARAF, BRAF, NRAS, CBL (ORPHA: 100976)
- Mosaic Vascular Malformations (RAS-related, syndromic) — KRAS, NRAS, BRAF, MAP2K1, RASA1 (ORPHA: 538)
- Melorheostosis with extraskeletal involvement — MAP2K1, KRAS (OMIM #155950; ORPHA: 2494)
- Mosaic PTPN11-related syndrome with lateralized overgrowth and vascular malformation — PTPN11
Abstract
Mosaic RASopathies are a clinically and genetically heterogeneous group of disorders caused by postzygotic activating variants in genes of the RAS/MAPK signaling pathway. Unlike germline RASopathies, mosaic forms typically present with localized or asymmetric features, including epidermal nevi, neurodevelopmental anomalies, vascular malformations, lymphatic anomalies, bone dysplasias, and — in their syndromic forms — multisystem involvement affecting the central nervous system, eyes, and skeleton. Despite growing recognition of individual entities, the overall clinical spectrum, genotype-phenotype correlations, and natural history of syndromic mosaic RASopathies remain poorly defined, largely due to the rarity and phenotypic variability of each condition. We invite all ITHACA centers to share clinical and molecular data on patients with any syndromic mosaic RASopathy, in order to build a multicenter cohort enabling systematic characterization of these disorders and identification of shared pathophysiological mechanisms and potential therapeutic targets.
Coordinating clinicians
- Alessandro Mussa; alessandro.mussa@unito.it
- Giuseppe Reynolds; giuseppe.reynolds@unito.it
Institution
Department of Public Health and Pediatrics, University of Turin – Regina Margherita Children’s Hospital, Turin, Italy
Specific requirements beyond clinical data and genotype data sharing
- Re-analysis of DNA samples: N
- Resampling of patients: N
- Linked to a translational/basic research project? N