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| == Cause == | == Cause == | ||
| The cause of SKS is gain-of-function ] in a gene ].<ref>{{cite journal |last1=Liu |first1=Andrew C. |last2=Shen |first2=Yang |last3=Serbinski |first3=Carolyn R. |last4=He |first4=Hongzhi |last5=Roman |first5=Destino |last6=Endale |first6=Mehari |last7=Aschbacher-Smith |first7=Lindsey |last8=King |first8=Katherine A. |last9=Granadillo |first9=Jorge L. |last10=López |first10=Isabel |last11=Krueger |first11=Darcy A. |last12=Dye |first12=Thomas J. |last13=Smith |first13=David F. |last14=Hogenesch |first14=John B. |last15=Prada |first15=Carlos E. |title=Clinical and functional studies of MTOR variants in Smith-Kingsmore syndrome reveal deficits of circadian rhythm and sleep-wake behavior |journal=Human Genetics and Genomics Advances |date=October 2024 |volume=5 |issue=4 |pages=100333 |doi=10.1016/j.xhgg.2024.100333}}</ref> | The cause of SKS is gain-of-function ] in a gene ].<ref>{{cite journal |last1=Liu |first1=Andrew C. |last2=Shen |first2=Yang |last3=Serbinski |first3=Carolyn R. |last4=He |first4=Hongzhi |last5=Roman |first5=Destino |last6=Endale |first6=Mehari |last7=Aschbacher-Smith |first7=Lindsey |last8=King |first8=Katherine A. |last9=Granadillo |first9=Jorge L. |last10=López |first10=Isabel |last11=Krueger |first11=Darcy A. |last12=Dye |first12=Thomas J. |last13=Smith |first13=David F. |last14=Hogenesch |first14=John B. |last15=Prada |first15=Carlos E. |title=Clinical and functional studies of MTOR variants in Smith-Kingsmore syndrome reveal deficits of circadian rhythm and sleep-wake behavior |journal=Human Genetics and Genomics Advances |date=October 2024 |volume=5 |issue=4 |pages=100333 |doi=10.1016/j.xhgg.2024.100333|pmc=11342114 }}</ref> | ||
| This disease is inherited in ] fashion, but most of the times it’s '']'' mutation.<ref>{{Cite journal |last1=Allen |first1=Andrew S. |last2=Berkovic |first2=Samuel F. |last3=Cossette |first3=Patrick |last4=Delanty |first4=Norman |last5=Dlugos |first5=Dennis |last6=Eichler |first6=Evan E. |last7=Epstein |first7=Michael P. |last8=Glauser |first8=Tracy |last9=Goldstein |first9=David B. |last10=Han |first10=Yujun |last11=Heinzen |first11=Erin L. |last12=Hitomi |first12=Yuki |last13=Howell |first13=Katherine B. |last14=Johnson |first14=Michael R. |last15=Kuzniecky |first15=Ruben |date=September 2013 |title=De novo mutations in epileptic encephalopathies |journal=Nature |language=en |volume=501 |issue=7466 |pages=217–221 |doi=10.1038/nature12439 |pmid=23934111 |pmc=3773011 |issn=1476-4687}}</ref><ref>{{Cite journal |last1=Mroske |first1=Cameron |last2=Rasmussen |first2=Kristen |last3=Shinde |first3=Deepali N. |last4=Huether |first4=Robert |last5=Powis |first5=Zoe |last6=Lu |first6=Hsiao-Mei |last7=Baxter |first7=Ruth M. |last8=McPherson |first8=Elizabeth |last9=Tang |first9=Sha |date=2015-11-05 |title=Germline activating MTOR mutation arising through gonadal mosaicism in two brothers with megalencephaly and neurodevelopmental abnormalities |journal=BMC Medical Genetics |volume=16 |issue=1 |pages=102 |doi=10.1186/s12881-015-0240-8 |doi-access=free |issn=1471-2350 |pmc=4635597 |pmid=26542245}}</ref> | This disease is inherited in ] fashion, but most of the times it’s '']'' mutation.<ref>{{Cite journal |last1=Allen |first1=Andrew S. |last2=Berkovic |first2=Samuel F. |last3=Cossette |first3=Patrick |last4=Delanty |first4=Norman |last5=Dlugos |first5=Dennis |last6=Eichler |first6=Evan E. |last7=Epstein |first7=Michael P. |last8=Glauser |first8=Tracy |last9=Goldstein |first9=David B. |last10=Han |first10=Yujun |last11=Heinzen |first11=Erin L. |last12=Hitomi |first12=Yuki |last13=Howell |first13=Katherine B. |last14=Johnson |first14=Michael R. |last15=Kuzniecky |first15=Ruben |date=September 2013 |title=De novo mutations in epileptic encephalopathies |journal=Nature |language=en |volume=501 |issue=7466 |pages=217–221 |doi=10.1038/nature12439 |pmid=23934111 |pmc=3773011 |issn=1476-4687}}</ref><ref>{{Cite journal |last1=Mroske |first1=Cameron |last2=Rasmussen |first2=Kristen |last3=Shinde |first3=Deepali N. |last4=Huether |first4=Robert |last5=Powis |first5=Zoe |last6=Lu |first6=Hsiao-Mei |last7=Baxter |first7=Ruth M. |last8=McPherson |first8=Elizabeth |last9=Tang |first9=Sha |date=2015-11-05 |title=Germline activating MTOR mutation arising through gonadal mosaicism in two brothers with megalencephaly and neurodevelopmental abnormalities |journal=BMC Medical Genetics |volume=16 |issue=1 |pages=102 |doi=10.1186/s12881-015-0240-8 |doi-access=free |issn=1471-2350 |pmc=4635597 |pmid=26542245}}</ref> | ||
Latest revision as of 03:45, 20 January 2025
Medical condition| Smith-Kingsmore syndrome | |
|---|---|
| Other names | SKS, Macrocephaly-intellectual disability-neurodevelopmental disorder-small thorax syndrome, MINDS syndrome |
 | |
| Smith-Kingsmore Syndrome is inherited in Autosomal Dominant fashion. | |
| Causes | Gain-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.
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
- https://www.orpha.net/en/disease/detail/457485?name=MINDS&mode=name
- "Smith-Kingsmore syndrome: MedlinePlus Genetics". medlineplus.gov. Retrieved 2025-01-06.
- "Orphanet: Clinical signs and symptoms". www.orpha.net. Retrieved 2025-01-06.
- 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.
- 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.
- 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.
- ^ "Smith-Kingsmore Syndrome - Symptoms, Causes, Treatment | NORD". rarediseases.org. Retrieved 2025-01-06.
- "Smith-Kingsmore Syndrome - Symptoms, Causes, Treatment | NORD". rarediseases.org. Retrieved 2025-01-06.
- "Managing/Treating SKS – SKS". Retrieved 2025-01-06.
- 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.