Megalencephaly syndromes are a spectrum of severe developmental neurological disorders associated with brain overgrowth. Two recent studies highlight the pathogenic role of somatic mutations in genes of the mTOR signalling pathway in the brains of patients with these conditions, providing hope for development of new treatments.
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References
Olney, A. H. Macrocephaly syndromes. Semin. Pediatr. Neurol. 14, 128–135 (2007).
Mirzaa, G. M. et al. Megalencephaly-capillary malformation (MCAP) and megalencephaly-polydactyly-polymicrogyria-hydrocephalus (MPPH) syndromes: two closely related disorders of brain overgrowth and abnormal brain and body morphogenesis. Am. J. Med. Genet. A 158, 269–291 (2012).
Tinkle, B. T., Schorry, E. K., Franz, D. N., Crone, K. R. & Saal, H. M. Epidemiology of hemimegalencephaly: a case series and review. Am. J. Med. Genet. A 139, 204–211 (2005).
Rivière, J.-B. et al. De novo germline and postzygotic mutations in AKT3, PIK3R2 and PIK3CA cause a spectrum of related megalencephaly syndromes. Nat. Genet. 44, 934–940 (2012).
Lee, J. H. et al. De novo somatic mutations in components of the PI3K-AKT3-mTOR pathway cause hemimegalencephaly. Nat. Genet. 44, 941–945 (2012).
Sheppard, K., Kinross, K. M., Solomon, B., Pearson. R. B. & Phillips, W. A. Targeting PI3 kinase/AKT/mTOR signaling in cancer. Crit. Rev. Oncog. 17, 69–95 (2012).
Wong, M. Mammalian target of rapamycin (mTOR) inhibition as a potential antiepileptogenic therapy: from tuberous sclerosis to common acquired epilepsies. Epilepsia 51, 27–36 (2010).
Lindhurst, M. J. et al. A mosaic activating mutation in AKT1 associated with the Proteus syndrome. N. Engl. J. Med. 365, 611–619 (2011).
Poduri, A. et al. Somatic activation of AKT3 causes hemispheric developmental brain malformations. Neuron 74, 41–48 (2012).
Franz, D. N. Everolimus: an mTOR inhibitor for the treatment of tuberous sclerosis. Expert Rev. Anticancer Ther. 11, 1181–1192 (2011).
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Striano, P., Zara, F. Mutations in mTOR pathway linked to megalencephaly syndromes. Nat Rev Neurol 8, 542–544 (2012). https://doi.org/10.1038/nrneurol.2012.178
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DOI: https://doi.org/10.1038/nrneurol.2012.178
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