De Novo Mutations in TUBB2A Cause Infantile-Onset Epilepsy and Mental Retardation and Literature Review

Objective: To investigate the clinical features of infantile-onset epilepsy and mental retardation caused by de novo mutations in TUBB2A and review the literature.

Methods: The clinical manifestations of two children with TUBB2A mutations in Pediatrics of Peking University, First Hospital were analyzed. Literature from Wanfang, Weipu, CNKI, and PubMed databases (self-built to August 2018) were searched and analyzed with the words “TUBB2A” and “epilepsy or convulsion” “epilepsy or convulsion.” Summary features included clinical presentation, EEG, imaging, treatment response, and genetic mutations.

Results: Two cases of de novo mutations in TUBB2A were females, with infantile-onset epilepsy and global developmental delay. Case 1 is a new hybrid heterozygous mutation: c.728C > T(excon4), p.P243L(NM_001069.2), MRI images showed white matter stunting, and the left frontal angle is slightly wider; case 2 is a newborn heterozygous mutation: c 0.743 (excon4) C > T, p.A248V (NM_001069.2), brain MRI showed bilateral anterior humeral gyrus with large cerebral gyrus, considering the possibility of giant gyrus deformity, bilateral frontal lobe abnormal signal, corpus callosum dysplasia. Literature retrieval was related with four references (in English), six cases were reported de novo mutations in TUBB2A, including this study has eight cases, three cases were p.A248V mutation. The subjects were infantile-onset epilepsy (spasms), with different levels of global developmental delay. MRI images were gyri developmental deformities, bad myelination and corpus callosum dysplasia. The seizure in p.P243L mutated was easy to control, and cerebral structural change was less severe.

Conclusion: TUBB2A mutations can cause infantile-onset epilepsy and global developmental delay, and different degree of brain malformations. The p.A248v mutation may be “hot spots” mutations. The p.P243L mutation caused a slight change in brain structure, and seizures were easily controlled.