title: Prevalence and clinical features of Costello syndrome and cardio-facio-cutaneous syndrome in Japan: findings from a nationwide epidemiological survey.
abstract: Costello syndrome and cardio-facio-cutaneous (CFC) syndrome are congenital anomaly syndromes characterized by a distinctive facial appearance, heart defects, and intellectual disability. Germline mutations in HRAS cause Costello syndrome, and mutations in KRAS, BRAF, and MAP2K1/2 (MEK1/2) cause CFC syndrome. Since the discovery of the causative genes, approximately 150 new patients with each syndrome have been reported. However, the clinico-epidemiological features of these disorders remain to be identified. In order to assess the prevalence, natural history, prognosis, and tumor incidence associated with these diseases, we conducted a nationwide prevalence study of patients with Costello and CFC syndromes in Japan. Based on the result of our survey, we estimated a total number of patients with either Costello syndrome or CFC syndrome in Japan of 99 (95% confidence interval, 77-120) and 157 (95% confidence interval, 86-229), respectively. The prevalences of Costello and CFC syndromes are estimated to be 1 in 1,290,000 and 1 in 810,000 individuals, respectively. An evaluation of 15 adult patients 18-32 years of age revealed that 12 had moderate to severe intellectual disability and most live at home without constant medical care. These results suggested that the number of adult patients is likely underestimated and our results represent a minimum prevalence. This is the first epidemiological study of Costello syndrome and CFC syndrome. Identifying patients older than 32 years of age and following up on the patients reported here is important to estimate the precise prevalence and the natural history of these disorders.
authors.affiliation: Department of Medical Genetics, Tohoku University School of Medicine, Sendai, Japan.
authors.forename: Yu
authors.initials: Y
authors.lastname: Abe
authors.forename: Yoko
authors.initials: Y
authors.lastname: Aoki
authors.forename: Shinichi
authors.initials: S
authors.lastname: Kuriyama
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kawame
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Okamoto
authors.forename: Kenji
authors.initials: K
authors.lastname: Kurosawa
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Ohashi
authors.forename: Seiji
authors.initials: S
authors.lastname: Mizuno
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Ogata
authors.forename: Shigeo
authors.initials: S
authors.lastname: Kure
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Niihori
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Matsubara
mesh_terms: D000293:Adolescent; D000328:Adult; D056685:Costello Syndrome / Q000150:complications / Q000453:epidemiology*; D003625:Data Collection; D004476:Ectodermal Dysplasia / Q000150:complications / Q000453:epidemiology*; D019066:Facies; D005183:Failure to Thrive / Q000150:complications / Q000453:epidemiology*; D018095:Germ-Line Mutation; D006330:Heart Defects, Congenital / Q000150:complications / Q000453:epidemiology*; D006801:Humans; D008607:Intellectual Disability; D007564:Japan / Q000453:epidemiology; D009369:Neoplasms / Q000209:etiology; D015995:Prevalence; D011379:Prognosis; D055815:Young Adult