mTOR mutations in Smith-Kingsmore syndrome: Four additional patients and a review

作者：Gordo G; Tenorio J; Arias P; Santos Simarro F; Garcia Minaur S; Moreno J C; Nevado J; Vallespin E; Rodriguez Laguna L; de Mena R; Dapia I; Palomares Bralo M; del Pozo A; Ibanez K; Silla J C; Barroso E; Ruiz Perez V L; Martinez Glez V^*; Lapunzina P^*

来源：Clinical Genetics, 2018, 93(4): 762-775.

DOI：10.1111/cge.13135

• constitutive mosaicism
• germline mosaicism
• gonadal mosaicism
• macrocephaly
• megalencephaly
• MINDS syndrome
• mTOR
• Smith-Kingsmore syndrome
• somatic mosaicism

Smith-Kingsmore syndrome (SKS) OMIM #616638, also known as MINDS syndrome (ORPHA 457485), is a rare autosomal dominant disorder reported so far in 23 patients. SKS is characterized by intellectual disability, macrocephaly/hemi/megalencephaly, and seizures. It is also associated with a pattern of facial dysmorphology and other non-neurological features. Germline or mosaic mutations of the mTOR gene have been detected in all patients. The mTOR gene is a key regulator of cell growth, cell proliferation, protein synthesis and synaptic plasticity, and the mTOR pathway (PI3K-AKT-mTOR) is highly regulated and critical for cell survival and apoptosis. Mutations in different genes in this pathway result in known rare diseases implicated in hemi/megalencephaly with epilepsy, as the tuberous sclerosis complex caused by mutations in TSC1 and TSC2, or the PIK3CA-related overgrowth spectrum (PROS). We here present 4 new cases of SKS, review all clinical and molecular aspects of this disorder, as well as some characteristics of the patients with only brain mTOR somatic mutations.

• 出版日期2018-4