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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.

Smith-Kingsmore Syndrome
Other names	SKS
Smith-Kingsmore Syndrome is inherited in Autosomal Dominant fashion.
Causes	Gain-of-function mutation in MTOR

Presentation

The signs of this disease are:

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

Cause

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

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

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.

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

Frequency

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

Treatment

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

History

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

References

1. "Smith-Kingsmore syndrome: MedlinePlus Genetics". medlineplus.gov. Retrieved 2025-01-06.
2. "Orphanet: Clinical signs and symptoms". www.orpha.net. Retrieved 2025-01-06.
3. "Clinical and functional studies of MTOR variants in Smith-Kingsmore syndrome reveal deficits of circadian rhythm and sleep-wake behavior". HGG Advances.
4. 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 (2013-09). "De novo mutations in epileptic encephalopathies". Nature. 501 (7466): 217–221. doi:10.1038/nature12439. ISSN 1476-4687. {{cite journal}}: Check date values in: |date= (help)
5. 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.{{cite journal}}: CS1 maint: PMC format (link) CS1 maint: unflagged free DOI (link)
6. ^ "Smith-Kingsmore Syndrome - Symptoms, Causes, Treatment | NORD". rarediseases.org. Retrieved 2025-01-06.
7. "Smith-Kingsmore Syndrome - Symptoms, Causes, Treatment | NORD". rarediseases.org. Retrieved 2025-01-06.
8. "Managing/Treating SKS – SKS". Retrieved 2025-01-06.
9. 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.