De novo HDAC8 mutation causes Rett-related disorder with distinctive facial features and multiple congenital anomalies

摘要

We present a unique 11-year-old girl showing clinical features of Rett-related disorder with distinctive facial features and multiple congenital anomalies including ocular hypertelorism, arched eyebrows, a broad nose, dental anomalies, congenital heart disease, truncal obesity, and epilepsy. A novel de flora mutation in histone deacetylase 8 (HDAC8) (c.652G T, p.Gly218Cys) was confirmed by whole exome sequencing and Sanger sequencing. X-chromosome inactivation analysis on DNA isolated from peripheral blood lymphocytes revealed a completely skewed pattern associated with an inactive maternal allele. Late clinical loss of acquired purposeful hand movements and psychomotor deterioration may be a feature of Rett-related disorder, while distinctive facial features and multiple congenital anomalies are reminiscent of Cornelia de Lange syndrome. (C) 2018 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.