XIII Congresso Brasileiro de Neurocirurgia Pediátrica

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Whole Exome Sequence of hemimegalencephaly treated surgically


Hemimegalencephaly (HME) involves overgrowth of an entire hemisphere. Is a rare, sporadic and nonfamilial congenital brain malformation with a low recurrence rate, even when associated with neuro-cutaneous syndromes. HME is classified as a malformation of cortical development due to non-neoplastic abnormal cell proliferation or apoptosis. Essays on the molecular pathogenesis and cellular cortical malformations can reveal information about associated mechanisms and contribute to new therapeutic approaches.

Materiais e Métodos/Casuística

Ten patients diagnosed with HME were selected following clinical criteria to hemispherotomy surgery. The samples were obtained from the biopsy of affected brain tissue, previously identified by preoperative image. The biopsied tissue was then fractionated into two parts. In the first, brain portions were coronally cut into 5-μm-thick sections, mounted on histological slides and were sent for anatomopathological analysis. The second part of the brain sample was sent for further analysis by mean of exome sequencing and ddPCR for validation and screening of mutation.


In order to investigate the role of the mTOR pathway and parallel pathways, Whole Exome Sequence was performed in all of the 10 patients. In two patients with HME, we identified missense mutations in the MTOR, HME 6584 (c.7255G>A, p.Glu2419Lys 10%ddPCR), HME 4146 (c.7498A>T, p.Leu7105Phe 6%ddPCR). Two other patients had missense mutations of the gene PIK3CA, HME 4149 (c.1624G>A, p.Glu542Lys 11% ddPCR) HME 4143 (c.1258T>C, p.Cys420Arg 22%ddPCR), this also had somatic mutations in the DEPDC5 in stop gain (c. 856C>T, p.Arg286* 5% ddPCR). The hypothesis through these results is that the somatic mutation of genes that are present in the mTOR pathway even being of low prevalence may be one of the genetic causes of HME.

Discussão e Conclusões

This study suggests that mutations in the PIK3CA, MTOR, DEPDC5 genes are associated with increased mTOR signaling in the affected brain regions. These results contribute to identification of the genetic association between HME and mTOR pathway, leading to a better understanding of the pathogenicity, what in future could lead to the discovery of novel therapies to seizures which are secondary to these developmental disorders.

Referências bibliográficas

Palavras Chaves

Hemimegalencephaly - mTor - Epilepsy


Neurocirurgia Pediátrica


Hospital das Clínicas de Ribeirão Preto - Sao Paulo - Brasil


Thiago Lyrio Teixeira, Camila Araújo Bernardino Garcia, Marcelo Volpon Santos, Wilson Araújo da Silva Júnior, Hélio Rubens Machado