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Features of a male with MACF1 mutation suffered from West syndrome：a case report and literature review

A 6-month-old boy was admitted to our pediatric department for repeated convulsions over 1 week. He mainly suffered from repeated spasms in clusters and global development delay. On neurologic examination, he could not raise his head, sit alone or turn over. Tendon reflexes and muscle tone were normal with negative pyramidal signs. He was diagnosed with West syndrome according to his clinical features and hypsarrhythmia on electroencephalograms. Brain magnetic resonance imaging revealed pachygyria and lissencephaly with more severe posterior involvement. A de novo MACF1 missense variant identified by Whole-exome sequencing: c.15266T＞C (pMet5089Thr, NM.012090.5) was conformed to autosomal dominant inheritance pattern. This mutation was classified as likely pathogenic according to ACMG guidelines and was predicted to be possibly functional damaging according to SIFT, Polyphen2, and Mutation Taster. Excluding our patient, there were 4 reports stating 13 cases who suffered from epilepsy with MACF1 variants through PubMed search[1-4]. It is suggested that MACF1 gene is potentially associated with epilepsy. He primarily underwent the therapy of ACTH combined with Topiramate which was subsequently adjusted as Vigabatrin with Topiramate due to respiratory infections. Reviewing his treatment history, ACTH seems to be less effective than Vigabatrin compared with the onset time of two different medications. A functional study indicated that MACF1-knockout brains of mice exhibited decreased numbers of GABAergic interneurons in cortex[5], suggesting a possible mechanism for epileptogenesis related to MACF1 mutation. It also indicates that Vigabatrin may be effective for infantile spasms combined with MACF1 mutation.
Keywords: MACF1, West syndrome, missense variants, Vigabatrin