TABLE I. Consideration of Endpoints for Costello and CFC Syndromes.

Endpoint considerations	Phenotypic characteristics
Cancer	CS: Cancer is seen in up to ~17% of individuals. Embryonal rhabdomyosarcoma is the most common CFC: May have a predisposition to acute lymphocytic leukemia though this is still unclear
Cardiac	CS and CFC: A cardiac phenotype is seen in about 80% of individuals and are somewhat similar in both groups  with hypertrophic cardiomyopathy, structure defects, and arrhythmias present
Cutaneous	CS: Cutaneous papilloma, redundant skin with deep creases, hyperkeratoses, generalized hyperpigmentation,  curly brittle hair CFC: Acquired melanocytic nevi, keratosis pilaris, ulerythema ophryogenes, infantile hemangiomas,  hyperkeratoses
Growth	CS and CFC: The vast majority have linear growth delays, feeding, and weight gain issues, gastroesophageal  dysmotility and reflux with many requiring gastrostomy tubes for feeding; some with growth hormone  deficiency
Musculoskeletal	CS and CFC: Generalized hypotonia, pectus deformities, joint laxity, kyphosis and/or scoliosis, abnormal bone  metabolism, osteopenia
Neurocognition	CS and CFC: Most with cognitive delay and/or learning disabilities ranging from mild to severe
Ocular	CS and CFC: Ocular abnormalities are seen in the majority of individuals with strabismus, nystagmus,  astigmatism, myopia, or hyperopia being common
Quality of life  (QOL)	CS and CFC: QOL endpoints can be a challenge because of its subjective nature. However, both CS and CFC  have multi-system organ involvement which can severely affect activities of daily living both in the family as a  whole and in the individual. Thus, QOL may be a valuable endpoint.