Of note, the development of Noonan syndrome, Costello syndrome, and neurofibromatosis type 1 are RASopathies, associated with mutations in the RAS cell signaling pathway. ERMS caused by genetically inherited mutations is cannot be morphologically distinguished from spontaneously acquired ERMS. Diagnosis
Rhabdomyosarcoma is diagnosed through the presence of embryonic myogenesis, or skeletal muscle formation, which can be identified through morphological examination as well as assays containing myogenic markers. Immunohistochemical assays use protein expression to determine the fusion status of the growth, differentiating fusion-negative rhabdomyosarcoma from fusion-positive  rhabdomyosarcoma. In the recent years, there has been a shift to use molecular classification over histological classification as histology alone does not predict the fusion type of rhabdomyosarcoma. The performance of molecular genetic tests as well as matching the genotypic result to the clinical presentation are necessary to confirm the diagnosis of rhabdomyosarcoma as well as identify a subtype. Immunochemistry
Fusion-status is determined through the expression of certain proteins that indicate muscle differentiation, or immunomarkers, although the specific assay panel used for diagnosis depends on the tumor morphology. These immunomarkers include desmin, muscle-specific actin, Myogenin, and MyoD1, the latter two being transcription factors that are involved in muscle differentiation. Embryonal rhabdomyosarcoma can be classified by its lack of PAX3–FOXO1 or PAX7–FOXO1 gene fusions, but approximately 20% of alveolar rhabdomyosarcomas are also determined to be fusion-negative. However, it is suggested that these "fusion-negative" ARMS may be a misclassification of embryonal rhabdomyosarcomas with predominantly dense morphology. The World Health Organization recommends considering "fusion-negative" ARMS as a "primitive form of ERMS".
Embryonal rhabdomyosarcoma is the most common in young children but there has been report of a second age peak in adolescence years. United States
As the most common form of soft tissue sarcoma, RMS affects around 4.5 people per million individuals under the age of 20 in the United States. From 1975 to 2005 in the United States, there is a lower incidence rate of rhabdomyosarcoma and better 5-year survival rates in Native Indian/Alaskan Native/Asian/Pacific Islander children compared to white or black children; however, Native Indian/Alaskan Native/Asian/Pacific Islander make up only 6.5% of the total population studied. Global
The incidence of RMS in Europe is similar to that of the United States, while the incidence in some parts of Asia is half of the United States. Etiology
Embryonal rhabdomyosarcoma results from copy number alterations as well as mutations in the RAS pathway. Genomic patterns associated with ERMS include the gains in chromosomes 8, 2, 11, 12, 13, and/or 20 and losses in chromosomes 10 and 15. Another common genomic alteration is loss of heterozygosity at chromosome 11p, the short arm of chromosome 11. It is believed that some of the identifying genetic mutations that can cause ERMS include p53 loss, RAS pathway activation, MYOD1 mutations. Patients in the fusion-negative group had different genetic mutation profiles than those in the fusion-positive group.Focusing on the fusion negative population, it was shown that the most fusion-negative tumors were caused by RAS isoform mutations.