Smith-Kingsmore syndrome

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Smith-Kingsmore syndrome
Other namesSKS, Macrocephaly-intellectual disability-neurodevelopmental disorder-small thorax syndrome, MINDS syndrome [1]
Autosomal dominant - en.svg
Smith-Kingsmore Syndrome is inherited in Autosomal Dominant fashion.
CausesGain-of-function mutation in MTOR

Smith-Kingsmore syndrome is a rare genetic disorder that is caused by gain-of-function mutation in an mTOR gene. The facial features of this syndrome are triangular face with a pointed chin, frontal bossing, hypertelorism, eyes with downslanting palpebral fissures, a flat nasal bridge, a long philtrum. [2]

Contents

Presentation

The signs of this disease are: [3]

Very frequent:

Frequent:

Occasional:

Very rare:

A photo showing 4 patients showing characteristic facial signs of Smith-Kingsmore syndrome. A-photo-showing-4-patients-with-sks.png
A photo showing 4 patients showing characteristic facial signs of Smith-Kingsmore syndrome.

Cause

The cause of SKS is gain-of-function mutation in a gene MTOR. [4]

This disease is inherited in Autosomal Dominant fashion, but most of the times it’s de-novo mutation. [5] [6]

Diagnosis

SKS is a rare condition so many physicians aren’t familiar with. A diagnosis of SKS is suspected based upon the identification of symptoms, a patient and family history and a thorough clinical evaluation. [7]

SKS can be confirmed with the detection of a germline or mosaic mutation in the MTOR gene. [7]

Frequency

Frequency of this disease is unknown, but all ethnic groups are equally affected [8]

Treatment

There is no cure for SKS, but management of some symptoms can be achieved [9]

History

SKS was first described by Dr Smith, L.D et al. in 2013. [10]

References

  1. ↑ https://www.orpha.net/en/disease/detail/457485?name=MINDS&mode=name
  2. ↑ "Smith-Kingsmore syndrome: MedlinePlus Genetics". medlineplus.gov. Retrieved 2025-01-06.
  3. ↑ "Orphanet: Clinical signs and symptoms". www.orpha.net. Retrieved 2025-01-06.
  4. ↑ Liu, Andrew C.; Shen, Yang; Serbinski, Carolyn R.; He, Hongzhi; Roman, Destino; Endale, Mehari; Aschbacher-Smith, Lindsey; King, Katherine A.; Granadillo, Jorge L.; López, Isabel; Krueger, Darcy A.; Dye, Thomas J.; Smith, David F.; Hogenesch, John B.; Prada, Carlos E. (October 2024). "Clinical and functional studies of MTOR variants in Smith-Kingsmore syndrome reveal deficits of circadian rhythm and sleep-wake behavior". Human Genetics and Genomics Advances. 5 (4): 100333. doi:10.1016/j.xhgg.2024.100333. PMC   11342114 .
  5. ↑ Allen, Andrew S.; Berkovic, Samuel F.; Cossette, Patrick; Delanty, Norman; Dlugos, Dennis; Eichler, Evan E.; Epstein, Michael P.; Glauser, Tracy; Goldstein, David B.; Han, Yujun; Heinzen, Erin L.; Hitomi, Yuki; Howell, Katherine B.; Johnson, Michael R.; Kuzniecky, Ruben (September 2013). "De novo mutations in epileptic encephalopathies". Nature. 501 (7466): 217–221. doi:10.1038/nature12439. ISSN   1476-4687. PMC   3773011 . PMID   23934111.
  6. ↑ Mroske, Cameron; Rasmussen, Kristen; Shinde, Deepali N.; Huether, Robert; Powis, Zoe; Lu, Hsiao-Mei; Baxter, Ruth M.; McPherson, Elizabeth; Tang, Sha (2015-11-05). "Germline activating MTOR mutation arising through gonadal mosaicism in two brothers with megalencephaly and neurodevelopmental abnormalities". BMC Medical Genetics. 16 (1): 102. doi: 10.1186/s12881-015-0240-8 . ISSN   1471-2350. PMC   4635597 . PMID   26542245.
  7. 1 2 "Smith-Kingsmore Syndrome - Symptoms, Causes, Treatment | NORD". rarediseases.org. Retrieved 2025-01-06.
  8. ↑ "Smith-Kingsmore Syndrome - Symptoms, Causes, Treatment | NORD". rarediseases.org. Retrieved 2025-01-06.
  9. ↑ "Managing/Treating SKS – SKS" . Retrieved 2025-01-06.
  10. ↑ Smith, Laurie D.; Saunders, Carol J.; Dinwiddie, Darrell L.; Atherton, Andrea M.; Miller, Neil A.; Soden, Sarah E.; Farrow, Emily G.; Abdelmoity, Ahmed T. G.; Kingsmore, Stephen F. (2013-09-04). "Exome Sequencing Reveals De Novo Germline Mutation of the Mammalian Target of Rapamycin (MTOR) in a Patient with Megalencephaly and Intractable Seizures" . Journal of Genomes and Exomes. 2013 (2): 63–72. doi:10.4137/JGE.S12583. ISSN   2253-5004.
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