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Clinical and radiological features of Japanese patients with a severe phenotype due to CASK mutations
Author(s) -
Takanashi Junichi,
Okamoto Nobuhiko,
Yamamoto Yuto,
Hayashi Shin,
Arai Hiroshi,
Takahashi Yukitoshi,
Maruyama Koichi,
Mizuno Seiji,
Shimakawa Shuichi,
Ono Hiroaki,
Oyanagi Reiki,
Kubo Satomi,
Barkovich A. James,
Inazawa Johji
Publication year - 2012
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.35640
Subject(s) - microcephaly , cerebellar hypoplasia (non human) , cask , corpus callosum , pediatrics , medicine , hypoplasia , epilepsy , radiological weapon , cerebellum , pathology , surgery , biology , genetics , psychiatry
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. © 2012 Wiley Periodicals, Inc.