An acute encephalopathy with reduced diffusion in BRAF-associated cardio-facio-cutaneous syndrome

• Published in: Brain & development (Tokyo. 1979) Vol. 41; no. 4; pp. 378 - 381
• Main Authors: Okuzono, Sayaka, Fukai, Ryoko, Noda, Marie, Miyake, Noriko, Lee, Sooyoung, Kaku, Noriyuki, Sanefuji, Masafumi, Akamine, Satoshi, Kanno, Shunsuke, Ishizaki, Yoshito, Torisu, Hiroyuki, Kira, Ryutaro, Matsumoto, Naomichi, Sakai, Yasunari, Ohga, Shouichi
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.04.2019
• Subjects: Acute encephalopathy; BRAF; Cardio-facio-cutaneous syndrome; Magnetic Resonance Imaging (MRI); BRAF; Magnetic Resonance Imaging (MRI); Cardio-facio-cutaneous syndrome; Acute encephalopathy
• ISSN: 0387-7604; 1872-7131
• DOI: 10.1016/j.braindev.2018.10.012

Cardio-facio-cutaneous syndrome (CFCS) is a rare genetic disorder characterized by cardiovascular anomalies, dysmorphic faces, ectodermal abnormalities and developmental delays. Mutations in BRAF and other RAS-MAPK pathway-associated genes are commonly identified in patients with CFCS. While this molecular pathway is known to be associated with neuro-inflammatory conditions, only one case with CFCS has been reported thus far to develop acute encephalopathy in childhood. A 3-year-old boy with dysmorphic features and mild psychomotor delay developed acute encephalopathy. After a 45-min long, generalized seizure, the magnetic resonance imaging revealed that the restricted diffusion signals spread to the bilateral subcortical white matters on day 1 of illness. Despite the 14 days of intensive care, the acute symptoms of encephalopathy left him intractable epilepsy and severe neurocognitive impairments. The whole-exome sequencing analysis identified a de novo heterozygous mutation of BRAF (NM_004333:p.Thr241Met) in this case. The present case suggests that the hyperactive condition of ERK signals might augment the development of acute encephalopathy and post-encephalopathic epilepsy in childhood.