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Smith-Kingsmore syndrome

From Wikipedia, the free encyclopedia
Smith-Kingsmore syndrome
Other namesSKS, Macrocephaly-intellectual disability-neurodevelopmental disorder-small thorax syndrome, MINDS syndrome [1]
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 a gene MTOR. 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]

Presentation

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The signs of this disease are:[3]

Very frequent:

  • Intellectual Disability
  • Macrocephaly

Frequent:

  • Abnormal facial shape
  • Abnormality of speech
  • Curly Hair
  • Seizure
  • Frontal bossing
  • Ventriculomegaly

Occasional:

  • Autistic Behaviour
  • Cafe-au-lait spot
  • Gait Disturbance
  • Hypertelorism
  • Hypotonia
  • Open mouth
  • Long philtrum
  • Polymicrogyria
  • Prominient forehead

Very rare:

  • Downslanted palpebral fissures
  • Depressed nasal bridge
  • Decreased circulating IgA level
A photo showing 4 patients showing characteristic facial signs of Smith-Kingsmore syndrome.

Cause

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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

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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

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

Treatment

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

History

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

References

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  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.
  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. ^ a b "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.