title: Epidemiological, clinical, and genetic landscapes of hypomyelinating leukodystrophies.
abstract: To determine the epidemiological, clinical, and genetic characteristics of congenital hypomyelinating leukodystrophies, including Pelizaeus-Merzbacher disease (PMD), we conducted a nationwide epidemiological survey in Japan. A two-step survey targeting all medical institutions specializing in pediatric neurology and childhood disability (919 institutes) in Japan was performed. Detailed information was collected for 101 patients (86 males and 15 females) with congenital hypomyelinating leukodystrophies. The prevalence of congenital hypomyelinating disorders was 0.78 per 100,000 people (0-19 years old), and the incidence was 1.40 per 100,000 live births. Molecular testing was performed in 75 % of patients, and PLP1 gene abnormalities were observed in 62 %. The incidence of PMD with PLP1 mutations was estimated to be 1.45 per 100,000 male live births and that for congenital hypomyelinating disorders with unknown cause to be 0.41 per 100,000 live births. Patients with PLP1 mutations showed a higher proportion of nystagmus and hypotonia, both of which tend to disappear over time. Our results constitute the first nationwide survey of congenital hypomyelinating disorders, and provide the epidemiological, clinical, and genetic landscapes of these disorders.
authors: National Institute of Neuroscience, National Center for Neurology and Psychiatry, 4-1-1 Ogawahigashi-cho, Kodaira, Tokyo, 187-8502, Japan.
authors: Yurika
authors: Y
authors: Numata
authors: Leo
authors: L
authors: Gotoh
authors: Akiko
authors: A
authors: Iwaki
authors: Kenji
authors: K
authors: Kurosawa
authors: Jun-Ichi
authors: J
authors: Takanashi
authors: Kimiko
authors: K
authors: Deguchi
authors: Toshiyuki
authors: T
authors: Yamamoto
authors: Hitoshi
authors: H
authors: Osaka
authors: Ken
authors: K
authors: Inoue
mesh_terms: D000293:Adolescent; D000328:Adult; D002353:Carrier State; D002648:Child; D002675:Child, Preschool; D005260:Female; D005817:Genetic Counseling; D006801:Humans; D015994:Incidence; D007223:Infant; D007564:Japan / Q000453:epidemiology; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009123:Muscle Hypotonia / Q000209:etiology; D009154:Mutation / Q000235:genetics; D009460:Neurologic Examination; D009759:Nystagmus, Pathologic / Q000209:etiology; D020371:Pelizaeus-Merzbacher Disease / Q000453:epidemiology* / Q000235:genetics*; D015995:Prevalence; D055815:Young Adult