Other Organizations & Additional Research

Boy with Smith-Kingsmore syndrome smiling, sitting cross-legged on couch

Acknowledgments

We are grateful for the support and interest of all the caring individuals who research mutations of the MTOR gene and Smith-Kingsmore syndrome. 

Much of this website’s content is based on Gordo et al (2018) and Mirzaa et al (2016). There is more research available on Smith-Kingsmore syndrome, and other organizations devoted to supporting individuals with rare genetic conditions. The following is a list of several of these resources, focused on those that include information on Smith-Kingsmore syndrome. 

Our goal is to provide accurate, science-based information on Smith-Kingsmore syndrome. We are especially grateful to Drs. Ghayda Mirzaa and Víctor Martínez-Glez and the members of our Medical & Scientific Advisory for their reviews and expert advice to make sure we achieve that goal.

National Institutes of Health (NIH) Websites

MedlinePlus brings together authoritative health information from the National Library of Medicine (NLM), the National Institutes of Health (NIH), and other government agencies and health-related organizations.

Smith-Kingsmore syndrome link for MedlinePlus
Logo for the Genetic and Rare Disease information center

The Genetic and Rare Diseases Information Center (GARD) is a program of the National Center for Advancing Translational Sciences (NCATS) and is funded by two parts of the NIH: NCATS and the National Human Genome Research Institute (NHGRI). GARD provides the public with access to current, reliable, and easy-to-understand information about rare or genetic diseases in English or Spanish.

Another website for research information on Smith-Kingsmore syndome is PubMed®. The U.S. NLM at the NIH maintains the searchable PubMed database. It comprises more than 30 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Smith-Kingsmore link for PubMed

Patient Advocacy Organizations

The National Organization for Rare Disorders (NORD) is a patient advocacy organization dedicated to individuals with rare diseases and the organizations that serve them. NORD, along with its more than 300 patient organization members, is committed to the identification, treatment, and cure of rare disorders through programs of education, advocacy, research, and patient services.

National Organization for Rare Disorders (NORD) logo
Smith-Kingsmore syndrome link for Global Genes

Global Genes is a global non-profit advocacy organization for individuals and families fighting rare and genetic diseases. The RARE Foundation Alliance is a network of over 500 foundations and support groups all connected to the rare disease community. Global Genes’ mission is to connect, empower and inspire the rare disease community.

Genetic Alliance is a nonprofit organization that engages individuals, families, and communities to transform health. The standalone website, Disease InfoSearch, is a great resource providing information from a database of more than 10,000 conditions and from thousands of partners.

Genetic Alliance Logo
Smith-Kingsmore syndrome link to Child Growth Foundation website

The Child Growth Foundation (CGF) is a leading UK charity focusing on the support and management of rare growth conditions affecting children and adults. CGF’s mission is that the UK has a system where all families affected by growth conditions can receive a clinical diagnosis and corresponding care plan, and no-one feels alone or isolated.

Research Materials

Some scientific research has been conducted and several papers are available with more information on this condition. In addition to the organizations above, the following is a list of some of the key research with links to the websites for each paper on Smith-Kingsmore syndrome and the MTOR gene:

 
Research on MTOR and Smith-Kingsmore Syndrome:
    1. Besterman AD, Althoff T, Elfferich P, Gutierrez-Mejia I, Sadik J, et al. Functional and structural analyses of novel Smith-Kingsmore Syndrome-Associated MTOR variants reveal potential new mechanisms and predictors of pathogenicity. PLOS Genetics 17(7): e1009651, 2021.
    2. Szczałuba K, Rydzanicz M, Walczak A, et al. Brain Tissue Low-Level Mosaicism for MTOR Mutation Causes Smith-Kingsmore Phenotype with Recurrent Hypoglycemia-A Novel Phenotype and a Further Proof for Testing of an Affected Tissue. Diagnostics (Basel). 2021;11(7):1269. Published 2021 Jul 15.
    3. Poole RL, Curry PDK, Marcinkute R, et al. Delineating the Smith-Kingsmore syndrome phenotype: Investigation of 16 patients with the MTOR c.5395G > A p.(Glu1799Lys) missense variant. Am J Med Genet A. 2021 Aug;185(8):2445-2454.
    4. Rodríguez-García ME, Cotrina-Vinagre FJ, Bellusci M, et al. A novel de novo MTOR gain-of-function variant in a patient with Smith-Kingsmore syndrome and Antiphospholipid syndrome. European Journal of Human Genetics. 2019 Sep;27(9):1369-1378. Epub 2019 May 3.
    5. Lee D, Jang J, Lee C. Smith–Kingsmore syndrome: The first report of a Korean patient with the MTOR germline mutation c.5395G>A p.(Glu1799Lys). Journal of Genetic Medicine 2019;16:27-30.
    6. Gordo G, Tenorio J, Arias P, et al. mTOR mutations in Smith-Kingsmore syndrome: Four additional patients and a review. Clin Genet. 2018;1–14.
    7. Moosa S, Bohrer-Rabel H, Altmuller J, et al. Smith-Kingsmore syndrome: a third family with the MTOR mutation c.5395G-A p.(Glu1799Lys) and evidence for paternal gonadal mosaicism. J. Med. Genet. 173A: 264-267, 2017.
    8. Moller RS, Weckhuysen S, Chipaux M, et al. Germline and somatic mutations in the MTOR gene in focal cortical dysplasia and epilepsy. Genet. 2: e118, 2016.
    9. Mirzaa GM, Campbell CD, Solovieff N, et al. Association of MTOR mutations with developmental brain disorders, including megalencephaly, focal cortical dysplasia, and pigmentary mosaicism. JAMA Neurol. 2016;73:836–845.
    10. Baynam G, Overkov A, Davis M, et al. A germline MTOR mutation in aboriginal Australian siblings with intellectual disability, dysmorphism, macrocephaly, and small thoraces. J. Med. Genet. 167A: 1659-1667, 2015.
    11. Mroske C, Rasmussen K, Shinde DN, et al. Germline activating MTOR mutation arising through gonadal mosaicism in two brothers with megalencephaly and neurodevelopmental abnormalities. BMC Med. Genet. 16: 102, 2015.
    12. Smith LD, Saunders CJ, Dinwiddie DL, et al. Exome sequencing reveals de novo germline mutation of mammalian target of rapamycin (MTOR) in a patient with megalencephaly and intractable seizures. Genomes Exomes 2: 63-72, 2013.
    13. Lee JH, Huynh M, Silhavy JL, et al. De novo somatic mutations in components of the PI3K-AKT3-mTOR pathway cause hemimegalencephaly. Nature Genet. 44: 941-945, 2012.
 
Other Related MTOR Gene Reviews:
    1. Zhang B, Guo D, Han L, et al. Hypothalamic orexin and mechanistic target of rapamycin activation mediate sleep dysfunction in a mouse model of tuberous sclerosis complex. Neurobiology of Disease, Volume 134, February 2020, 104615.
    2. Ramanathan C, et al. mTOR signaling regulates central and peripheral circadian clock function. PLoS Genet. 2018;14:e1007369.
    3. Sabatini DM. Twenty-five years of mTOR: uncovering the link from nutrients to growth. Proc Natl Acad Sci USA. 2017; 114:11818–11825.

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