SKS
MCID: SMT020
MIFTS: 35

Smith-Kingsmore Syndrome (SKS)

Categories: Fetal diseases, Genetic diseases, Mental diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Smith-Kingsmore Syndrome

MalaCards integrated aliases for Smith-Kingsmore Syndrome:

Name: Smith-Kingsmore Syndrome 58 54 26 60 76 38 30 6
Macrocephaly-Intellectual Disability-Neurodevelopmental Disorder-Small Thorax Syndrome 58 54 26 60 76 17
Minds Syndrome 58 54 26 60 76
Sks 58 26 76
Macrocephaly, Seizures, Intellectual Disability, Umbilical Hernia, and Facial Dysmorphism 54 26
Macrocephaly, Seizures, Mental Retardation, Umbilical Hernia, and Facial Dysmorphism 58 76
Syndrome, Smith-Kingsmore 41

Characteristics:

Orphanet epidemiological data:

60
macrocephaly-intellectual disability-neurodevelopmental disorder-small thorax syndrome
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal; Age of death: early childhood;

OMIM:

58
Inheritance:
autosomal dominant

Miscellaneous:
variable features present


HPO:

33
smith-kingsmore syndrome:
Inheritance autosomal dominant inheritance


Classifications:



Summaries for Smith-Kingsmore Syndrome

Genetics Home Reference : 26 Smith-Kingsmore syndrome is a neurological disorder characterized by a head that is larger than normal (macrocephaly), intellectual disability, and seizures. In some people with this condition, the ability to speak is delayed or never develops. Some children with Smith-Kingsmore syndrome have features of a behavioral condition called attention deficit hyperactivity disorder (ADHD) or autism spectrum disorder, which is characterized by impaired communication and social interaction. Structural brain abnormalities may also be present in affected individuals. For example, one or both sides of the brain may be enlarged (hemimegalencephaly or megalencephaly) or have too many ridges on the surface (polymicrogyria), or the fluid-filled spaces near the center of the brain (ventricles) may be bigger than normal (ventriculomegaly).

MalaCards based summary : Smith-Kingsmore Syndrome, also known as macrocephaly-intellectual disability-neurodevelopmental disorder-small thorax syndrome, is related to actinic keratosis and neuroblastoma 1. An important gene associated with Smith-Kingsmore Syndrome is MTOR (Mechanistic Target Of Rapamycin Kinase), and among its related pathways/superpathways is mTOR signaling pathway. Affiliated tissues include brain, prostate and skin, and related phenotypes are macrocephaly and hypertelorism

OMIM : 58 Smith-Kingsmore syndrome is a rare autosomal dominant syndromic intellectual disability syndrome characterized by macrocephaly, seizures, umbilical hernia, and facial dysmorphic features including frontal bossing, midface hypoplasia, small chin, hypertelorism with downslanting palpebral fissures, depressed nasal bridge, smooth philtrum, and thin upper lip (Smith et al., 2013; Baynam et al., 2015). (616638)

UniProtKB/Swiss-Prot : 76 Smith-Kingsmore syndrome: An autosomal dominant syndrome characterized by intellectual disability, macrocephaly, seizures, umbilical hernia, and facial dysmorphic features.

Related Diseases for Smith-Kingsmore Syndrome

Diseases related to Smith-Kingsmore Syndrome via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 103)
# Related Disease Score Top Affiliating Genes
1 actinic keratosis 11.1
2 neuroblastoma 1 10.6
3 melanoma 10.5
4 ewing sarcoma 10.4
5 ovarian cancer 10.3
6 antiphospholipid syndrome 10.3
7 breast cancer 10.3
8 salla disease 10.3
9 hepatocellular carcinoma 10.2
10 keratoconus 10.2
11 sarcoma 10.2
12 leiomyosarcoma 10.2
13 adenocarcinoma 10.1
14 limb-mammary syndrome 10.0
15 hypoxia 10.0
16 horns in sheep 10.0
17 ovarian cancer 1 10.0
18 glioma 10.0
19 diabetes mellitus, noninsulin-dependent 9.9
20 multiple sclerosis 9.9
21 holt-oram syndrome 9.9
22 renal cell carcinoma, nonpapillary 9.9
23 rheumatoid arthritis 9.9
24 lung cancer 9.9
25 wilms tumor 5 9.9
26 lung cancer susceptibility 3 9.9
27 wilms tumor 6 9.9
28 leukemia 9.9
29 periodontal disease 9.9
30 breast adenocarcinoma 9.9
31 ovary adenocarcinoma 9.9
32 spindle cell sarcoma 9.9
33 spindle cell hemangioma 9.9
34 periodontitis 9.9
35 herpes simplex 9.9
36 neuropathy 9.9
37 saethre-chotzen syndrome 9.7
38 alzheimer disease 9.7
39 blood group, kidd system 9.7
40 blood group--wright antigen 9.7
41 colorectal cancer 9.7
42 thyroid carcinoma, familial medullary 9.7
43 neurofibromatosis, type iv, of riccardi 9.7
44 pelger-huet anomaly 9.7
45 pheochromocytoma 9.7
46 prostate cancer 9.7
47 retinoblastoma 9.7
48 schizophrenia 9.7
49 alstrom syndrome 9.7
50 disorganization, mouse, homolog of 9.7

Graphical network of the top 20 diseases related to Smith-Kingsmore Syndrome:



Diseases related to Smith-Kingsmore Syndrome

Symptoms & Phenotypes for Smith-Kingsmore Syndrome

Human phenotypes related to Smith-Kingsmore Syndrome:

33 (show all 33)
# Description HPO Frequency HPO Source Accession
1 macrocephaly 33 HP:0000256
2 hypertelorism 33 HP:0000316
3 frontal bossing 33 HP:0002007
4 intellectual disability 33 HP:0001249
5 seizures 33 HP:0001250
6 depressed nasal bridge 33 HP:0005280
7 umbilical hernia 33 HP:0001537
8 short nose 33 HP:0003196
9 smooth philtrum 33 HP:0000319
10 hypoglycemia 33 HP:0001943
11 long philtrum 33 HP:0000343
12 strabismus 33 HP:0000486
13 thrombocytopenia 33 HP:0001873
14 wide mouth 33 HP:0000154
15 rhizomelia 33 HP:0008905
16 downslanted palpebral fissures 33 HP:0000494
17 open mouth 33 HP:0000194
18 thin upper lip vermilion 33 HP:0000219
19 high forehead 33 HP:0000348
20 midface retrusion 33 HP:0011800
21 wide anterior fontanel 33 HP:0000260
22 decreased circulating iga level 33 HP:0002720
23 curly hair 33 HP:0002212
24 short distal phalanx of finger 33 HP:0009882
25 diastasis recti 33 HP:0001540
26 generalized hypotonia 33 HP:0001290
27 deep plantar creases 33 HP:0001869
28 deep palmar crease 33 HP:0006191
29 cafe-au-lait spot 33 HP:0000957
30 short chin 33 HP:0000331
31 perisylvian polymicrogyria 33 HP:0012650
32 hemimegalencephaly 33 HP:0007206
33 short proximal phalanx of finger 33 HP:0010241

Symptoms via clinical synopsis from OMIM:

58
Head And Neck Head:
macrocephaly
frontal bossing
large anterior fontanel
tall forehead

Neurologic Central Nervous System:
intellectual disability
perisylvian polymicrogyria
seizures (in some patients)
mild prominence of the ventricular system
hypogenesis of the body and the splenium of the corpus callosum
more
Abdomen External Features:
umbilical hernia
diastasis recti

Laboratory Abnormalities:
hypoglycemia

Hematology:
thrombocytopenia

Growth Other:
large for gestational age

Muscle Soft Tissue:
hypotonia

Neurologic Behavioral Psychiatric Manifestations:
autistic features

Skeletal Hands:
short distal phalanges
short proximal phalanges
deep palmar creases

Chest External Features:
small thorax

Genitourinary Kidneys:
renal asymmetry

Skin Nails Hair Nails:
small toenails

Cardiovascular Heart:
aortic sinus to right atrial fistula

Head And Neck Eyes:
hypertelorism
strabismus
downslanting palpebral fissures

Head And Neck Nose:
depressed nasal bridge
short nose

Head And Neck Mouth:
smooth philtrum
long philtrum
thin upper lip
macrostomia
open mouth posture

Genitourinary External Genitalia Male:
cryptorchidism

Skin Nails Hair Hair:
curly hair
wavy hair

Skeletal Feet:
deep plantar creases
short distal phalanges

Head And Neck Face:
midface hypoplasia
small chin

Skeletal Limbs:
rhizomelic limb shortening

Abdomen Gastrointestinal:
poor feeding

Skin Nails Hair Skin:
cafe-au-lait spots

Immunology:
iga deficiency

Growth Weight:
birth length >3 sd

Clinical features from OMIM:

616638

Drugs & Therapeutics for Smith-Kingsmore Syndrome

Search Clinical Trials , NIH Clinical Center for Smith-Kingsmore Syndrome

Genetic Tests for Smith-Kingsmore Syndrome

Genetic tests related to Smith-Kingsmore Syndrome:

# Genetic test Affiliating Genes
1 Smith-Kingsmore Syndrome 30 MTOR

Anatomical Context for Smith-Kingsmore Syndrome

MalaCards organs/tissues related to Smith-Kingsmore Syndrome:

42
Brain, Prostate, Skin, Thyroid, Myeloid, Pons, Colon

Publications for Smith-Kingsmore Syndrome

Articles related to Smith-Kingsmore Syndrome:

# Title Authors Year
1
A novel de novo MTOR gain-of-function variant in a patient with Smith-Kingsmore syndrome and Antiphospholipid syndrome. ( 31053780 )
2019
2
Smith-Kingsmore syndrome: A third family with the MTOR mutation c.5395G>A p.(Glu1799Lys) and evidence for paternal gonadal mosaicism. ( 27753196 )
2017
3
Association of MTOR Mutations With Developmental Brain Disorders, Including Megalencephaly, Focal Cortical Dysplasia, and Pigmentary Mosaicism. ( 27159400 )
2016
4
Germline and somatic mutations in the MTOR gene in focal cortical dysplasia and epilepsy. ( 27830187 )
2016
5
A germline MTOR mutation in Aboriginal Australian siblings with intellectual disability, dysmorphism, macrocephaly, and small thoraces. ( 25851998 )
2015

Variations for Smith-Kingsmore Syndrome

UniProtKB/Swiss-Prot genetic disease variations for Smith-Kingsmore Syndrome:

76
# Symbol AA change Variation ID SNP ID
1 MTOR p.Glu1799Lys VAR_075072 rs863225264
2 MTOR p.Trp1490Arg VAR_078832
3 MTOR p.Met1595Ile VAR_078833 rs869312671
4 MTOR p.Ala1832Thr VAR_078835 rs369088781
5 MTOR p.Phe1888Cys VAR_078836 rs869312666
6 MTOR p.Met2327Ile VAR_078840 rs878855328

ClinVar genetic disease variations for Smith-Kingsmore Syndrome:

6 (show all 18)
# Gene Variation Type Significance SNP ID Assembly Location
1 MTOR NM_004958.3(MTOR): c.4448G> T (p.Cys1483Phe) single nucleotide variant Pathogenic rs786205165 GRCh37 Chromosome 1, 11217230: 11217230
2 MTOR NM_004958.3(MTOR): c.4448G> T (p.Cys1483Phe) single nucleotide variant Pathogenic rs786205165 GRCh38 Chromosome 1, 11157173: 11157173
3 MTOR NM_004958.3(MTOR): c.5395G> A (p.Glu1799Lys) single nucleotide variant Conflicting interpretations of pathogenicity rs863225264 GRCh37 Chromosome 1, 11190804: 11190804
4 MTOR NM_004958.3(MTOR): c.5395G> A (p.Glu1799Lys) single nucleotide variant Conflicting interpretations of pathogenicity rs863225264 GRCh38 Chromosome 1, 11130747: 11130747
5 MTOR NM_004958.3(MTOR): c.5663T> G (p.Phe1888Cys) single nucleotide variant Pathogenic rs869312666 GRCh37 Chromosome 1, 11189846: 11189846
6 MTOR NM_004958.3(MTOR): c.5663T> G (p.Phe1888Cys) single nucleotide variant Pathogenic rs869312666 GRCh38 Chromosome 1, 11129789: 11129789
7 MTOR NM_004958.3(MTOR): c.4785G> A (p.Met1595Ile) single nucleotide variant Pathogenic rs869312671 GRCh37 Chromosome 1, 11204792: 11204792
8 MTOR NM_004958.3(MTOR): c.4785G> A (p.Met1595Ile) single nucleotide variant Pathogenic rs869312671 GRCh38 Chromosome 1, 11144735: 11144735
9 MTOR NM_004958.3(MTOR): c.505-2A> G single nucleotide variant Uncertain significance rs869312706 GRCh37 Chromosome 1, 11316251: 11316251
10 MTOR NM_004958.3(MTOR): c.505-2A> G single nucleotide variant Uncertain significance rs869312706 GRCh38 Chromosome 1, 11256194: 11256194
11 MTOR NM_004958.3(MTOR): c.6981G> A (p.Met2327Ile) single nucleotide variant Pathogenic rs878855328 GRCh37 Chromosome 1, 11177096: 11177096
12 MTOR NM_004958.3(MTOR): c.6981G> A (p.Met2327Ile) single nucleotide variant Pathogenic rs878855328 GRCh38 Chromosome 1, 11117039: 11117039
13 MTOR NM_004958.3(MTOR): c.4606A> G (p.Ile1536Val) single nucleotide variant Uncertain significance rs886041096 GRCh37 Chromosome 1, 11206813: 11206813
14 MTOR NM_004958.3(MTOR): c.4606A> G (p.Ile1536Val) single nucleotide variant Uncertain significance rs886041096 GRCh38 Chromosome 1, 11146756: 11146756
15 MTOR NM_004958.3(MTOR): c.5653G> A (p.Val1885Ile) single nucleotide variant Uncertain significance rs139043855 GRCh37 Chromosome 1, 11189856: 11189856
16 MTOR NM_004958.3(MTOR): c.5653G> A (p.Val1885Ile) single nucleotide variant Uncertain significance rs139043855 GRCh38 Chromosome 1, 11129799: 11129799
17 MTOR NM_004958.3(MTOR): c.743C> T (p.Thr248Ile) single nucleotide variant Uncertain significance GRCh37 Chromosome 1, 11313993: 11313993
18 MTOR NM_004958.3(MTOR): c.743C> T (p.Thr248Ile) single nucleotide variant Uncertain significance GRCh38 Chromosome 1, 11253936: 11253936

Expression for Smith-Kingsmore Syndrome

Search GEO for disease gene expression data for Smith-Kingsmore Syndrome.

Pathways for Smith-Kingsmore Syndrome

Pathways related to Smith-Kingsmore Syndrome according to KEGG:

38
# Name Kegg Source Accession
1 mTOR signaling pathway hsa04150

GO Terms for Smith-Kingsmore Syndrome

Sources for Smith-Kingsmore Syndrome

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
20 FMA
29 GO
30 GTR
31 HGMD
32 HMDB
33 HPO
34 ICD10
35 ICD10 via Orphanet
36 ICD9CM
37 IUPHAR
38 KEGG
39 LifeMap
41 LOVD
43 MedGen
45 MeSH
46 MESH via Orphanet
47 MGI
50 NCI
51 NCIt
52 NDF-RT
55 NINDS
56 Novoseek
58 OMIM
59 OMIM via Orphanet
63 PubMed
65 QIAGEN
70 SNOMED-CT via HPO
71 SNOMED-CT via Orphanet
72 TGDB
73 Tocris
74 UMLS
75 UMLS via Orphanet
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