2. Academic Validation
  3. mTOR mutations in Smith-Kingsmore syndrome: Four additional patients and a review

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

  • Clin Genet. 2018 Apr;93(4):762-775. doi: 10.1111/cge.13135.
G Gordo 1 2 3,  J Tenorio 1 2,  P Arias 1 2,  F Santos-Simarro 1 4,  S García-Miñaur 1 4,  J C Moreno 1 2,  J Nevado 1 5,  E Vallespin 1 5,  L Rodriguez-Laguna 1 3,  R de Mena 1 5,  I Dapia 1 2,  M Palomares-Bralo 1 5,  Á Del Pozo 1 6,  K Ibañez 1 6,  J C Silla 1 6,  E Barroso 1 2,  V L Ruiz-Pérez 1 7,  V Martinez-Glez 1 3 4,  P Lapunzina 1 2 4
Affiliations

Affiliations

  • 1 Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), ISCIII, Madrid, Spain.
  • 2 Molecular Endocrinology Section, Overgrowth Syndromes Laboratory, Instituto de Genética Médica y Molecular (INGEMM), IdiPAZ, Hospital Universitario la Paz, Universidad Autónoma de Madrid (UAM), Madrid, Spain.
  • 3 Vascular Malformations Section, Instituto de Genética Médica y Molecular (INGEMM), IdiPAZ, Hospital Universitario la Paz, Universidad Autónoma de Madrid (UAM), Madrid, Spain.
  • 4 Clinical Genetics Section, Instituto de Genética Médica y Molecular (INGEMM), IdiPAZ, Hospital Universitario la Paz, Universidad Autónoma de Madrid (UAM), Madrid, Spain.
  • 5 Structural and Functional Genomics Section, Instituto de Genética Médica y Molecular (INGEMM), IdiPAZ, Hospital Universitario la Paz, Universidad Autónoma de Madrid (UAM), Madrid, Spain.
  • 6 Bioinformatics Section, Instituto de Genética Médica y Molecular (INGEMM), IdiPAZ, Hospital Universitario la Paz, Universidad Autónoma de Madrid (UAM), Madrid, Spain.
  • 7 IIB, Instituto de Investigación "Alberto Sols", Universidad Autónoma de Madrid (UAM), Madrid, Spain.
PMID: 28892148 DOI: 10.1111/cge.13135
Abstract

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.

Keywords

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

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