title: Clinical and radiological features of Japanese patients with a severe phenotype due to CASK mutations.
abstract: Heterozygous loss of function mutations of CASK at Xp11.4 in females cause severe intellectual disability (ID) and microcephaly with pontine and cerebellar hypoplasia (MICPCH). However, the longitudinal clinical and radiological course of affected patients, including patterns of postnatal growth, has not been described. Neurodevelopmental and imaging information was retrospectively accrued for 16 Japanese (15 female and 1 male) patients with ID and MICPCH associated with CASK mutations. All records were analyzed; patient age ranged from 2 to 16 years at the time of the most recent examinations. The growth pattern, neurological development, neurological signs/symptoms, and facial features were similar in the 15 female patients. Their head circumference at birth was within the normal range in about half, and their height and weight were frequently normal. This was followed by early development of severe microcephaly and postnatal growth retardation. The patients acquired head control almost normally between 3 and 6 months, followed by motor delay. More than half of the female patients had epilepsy. Their MRIs showed microcephaly, brainstem, and cerebellar hypoplasia in early infancy, and a normal or large appearing corpus callosum. The male patient showed a more severe clinical phenotype. These uniform clinical and radiological features should facilitate an early diagnosis and be useful for medical care of females with ID and MICPCH associated with CASK mutations.
authors.affiliation: Department of Pediatrics, Kameda Medical Center, Kamogawa, Japan. jtaka44@hotmail.co.jp
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Takanashi
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Okamoto
authors.forename: Yuto
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: Shin
authors.initials: S
authors.lastname: Hayashi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Arai
authors.forename: Yukitoshi
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Koichi
authors.initials: K
authors.lastname: Maruyama
authors.forename: Seiji
authors.initials: S
authors.lastname: Mizuno
authors.forename: Shuichi
authors.initials: S
authors.lastname: Shimakawa
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Ono
authors.forename: Reiki
authors.initials: R
authors.lastname: Oyanagi
authors.forename: Satomi
authors.initials: S
authors.lastname: Kubo
authors.forename: A James
authors.initials: AJ
authors.lastname: Barkovich
authors.forename: Johji
authors.initials: J
authors.lastname: Inazawa
mesh_terms: D000293:Adolescent; D044466:Asian People; D001933:Brain Stem / Q000473:pathology; D002526:Cerebellar Diseases / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D002531:Cerebellum / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D004827:Epilepsy / Q000175:diagnosis / Q000235:genetics / Q000473:pathology; D005260:Female; D051528:Guanylate Kinases / Q000235:genetics*; D006801:Humans; D008607:Intellectual Disability / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D009154:Mutation; D010641:Phenotype; D012189:Retrospective Studies
chemical_list: C106868:CASK kinases; D051528:Guanylate Kinases