SSMS
MCID: SZR028
MIFTS: 37

Seizures, Scoliosis, and Macrocephaly/microcephaly Syndrome (SSMS)

Categories: Bone diseases, Genetic diseases, Metabolic diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Seizures, Scoliosis, and Macrocephaly/microcephaly Syndrome

MalaCards integrated aliases for Seizures, Scoliosis, and Macrocephaly/microcephaly Syndrome:

Name: Seizures, Scoliosis, and Macrocephaly/microcephaly Syndrome 56 73
Seizures, Scoliosis, and Macrocephaly Syndrome 56 29 6 39
Seizures-Scoliosis-Macrocephaly Syndrome 58 73
Ssms 56 73
Ssm Syndrome 58

Characteristics:

OMIM:

56
Inheritance:
autosomal recessive

Miscellaneous:
onset in infancy
variable age at onset of seizures


HPO:

31
seizures, scoliosis, and macrocephaly/microcephaly syndrome:
Inheritance autosomal recessive inheritance
Onset and clinical course infantile onset


Classifications:

Orphanet: 58  
Rare neurological diseases
Inborn errors of metabolism


Summaries for Seizures, Scoliosis, and Macrocephaly/microcephaly Syndrome

OMIM : 56 Seizures, scoliosis, and macrocephaly/microcephaly syndrome (SSMS) is an autosomal recessive neurodevelopmental disorder characterized by global developmental delay apparent from early infancy, impaired intellectual development, behavioral problems, poor or absent speech, seizures, dysmorphic facial features with macro- or microcephaly, and skeletal abnormalities, including scoliosis and delayed bone age. Other features may include hypotonia, gastrointestinal problems, and exostoses (summary by Gentile et al., 2019). (616682)

MalaCards based summary : Seizures, Scoliosis, and Macrocephaly/microcephaly Syndrome, also known as seizures, scoliosis, and macrocephaly syndrome, is related to superficial spreading melanoma and atrial standstill 1. An important gene associated with Seizures, Scoliosis, and Macrocephaly/microcephaly Syndrome is EXT2 (Exostosin Glycosyltransferase 2). Affiliated tissues include skin, bone and breast, and related phenotypes are global developmental delay and delayed speech and language development

UniProtKB/Swiss-Prot : 73 Seizures, scoliosis, and macrocephaly/microcephaly syndrome: An autosomal recessive syndrome characterized by seizures, intellectual disability, hypotonia, scoliosis, macrocephaly, hypertelorism and renal dysfunction.

Related Diseases for Seizures, Scoliosis, and Macrocephaly/microcephaly Syndrome

Diseases related to Seizures, Scoliosis, and Macrocephaly/microcephaly Syndrome via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 22)
# Related Disease Score Top Affiliating Genes
1 superficial spreading melanoma 11.6
2 atrial standstill 1 10.4
3 galactosemia i 10.3
4 lentigines 10.2
5 alstrom syndrome 10.2
6 melanoma, cutaneous malignant 10 10.2
7 hypertrophic cardiomyopathy 10.2
8 melanoma 10.2
9 cataract 10.2
10 hepatocellular carcinoma 10.1
11 multiple system atrophy 1 10.1
12 supranuclear palsy, progressive, 1 10.1
13 dermatitis, atopic 10.1
14 ptosis 10.1
15 nodular malignant melanoma 10.1
16 hepatitis c 10.1
17 hepatitis b 10.1
18 myopathy 10.1
19 aminoaciduria 10.1
20 lentigo maligna melanoma 10.1
21 splenomegaly 10.1
22 metabolic myopathy 10.1

Graphical network of the top 20 diseases related to Seizures, Scoliosis, and Macrocephaly/microcephaly Syndrome:



Diseases related to Seizures, Scoliosis, and Macrocephaly/microcephaly Syndrome

Symptoms & Phenotypes for Seizures, Scoliosis, and Macrocephaly/microcephaly Syndrome

Human phenotypes related to Seizures, Scoliosis, and Macrocephaly/microcephaly Syndrome:

58 31 (show all 49)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 global developmental delay 58 31 hallmark (90%) Very frequent (99-80%) HP:0001263
2 delayed speech and language development 58 31 hallmark (90%) Very frequent (99-80%) HP:0000750
3 reduced bone mineral density 58 31 hallmark (90%) Very frequent (99-80%) HP:0004349
4 seizure 31 hallmark (90%) HP:0001250
5 hypertelorism 58 31 frequent (33%) Frequent (79-30%) HP:0000316
6 muscular hypotonia 58 31 frequent (33%) Frequent (79-30%) HP:0001252
7 scoliosis 58 31 frequent (33%) Frequent (79-30%) HP:0002650
8 macrocephaly 58 31 frequent (33%) Frequent (79-30%) HP:0000256
9 gastroesophageal reflux 58 31 frequent (33%) Frequent (79-30%) HP:0002020
10 intellectual disability, mild 58 31 frequent (33%) Frequent (79-30%) HP:0001256
11 cryptorchidism 58 31 frequent (33%) Frequent (79-30%) HP:0000028
12 autism 58 31 frequent (33%) Frequent (79-30%) HP:0000717
13 long philtrum 58 31 frequent (33%) Frequent (79-30%) HP:0000343
14 constipation 58 31 frequent (33%) Frequent (79-30%) HP:0002019
15 intellectual disability, moderate 58 31 frequent (33%) Frequent (79-30%) HP:0002342
16 bulbous nose 58 31 frequent (33%) Frequent (79-30%) HP:0000414
17 abnormality of the kidney 58 31 frequent (33%) Frequent (79-30%) HP:0000077
18 broad-based gait 58 31 frequent (33%) Frequent (79-30%) HP:0002136
19 abnormality of the skin 58 31 frequent (33%) Frequent (79-30%) HP:0000951
20 abnormality of the outer ear 58 31 frequent (33%) Frequent (79-30%) HP:0000356
21 overlapping toe 58 31 frequent (33%) Frequent (79-30%) HP:0001845
22 nausea 58 31 frequent (33%) Frequent (79-30%) HP:0002018
23 microcephaly 58 31 occasional (7.5%) Occasional (29-5%) HP:0000252
24 intellectual disability, severe 58 31 occasional (7.5%) Occasional (29-5%) HP:0010864
25 prominent forehead 58 31 occasional (7.5%) Occasional (29-5%) HP:0011220
26 atrial septal defect 58 31 occasional (7.5%) Occasional (29-5%) HP:0001631
27 polyhydramnios 58 31 occasional (7.5%) Occasional (29-5%) HP:0001561
28 high forehead 58 31 occasional (7.5%) Occasional (29-5%) HP:0000348
29 exostoses 58 31 occasional (7.5%) Occasional (29-5%) HP:0100777
30 flat forehead 58 31 occasional (7.5%) Occasional (29-5%) HP:0004425
31 patent ductus arteriosus 31 very rare (1%) HP:0001643
32 coarse facial features 31 HP:0000280
33 seizures 58 Very frequent (99-80%)
34 pes planus 31 HP:0001763
35 stereotypy 31 HP:0000733
36 feeding difficulties 31 HP:0011968
37 strabismus 31 HP:0000486
38 motor delay 31 HP:0001270
39 clinodactyly of the 5th finger 31 HP:0004209
40 preauricular skin tag 31 HP:0000384
41 ventricular septal defect 31 HP:0001629
42 nail dysplasia 31 HP:0002164
43 sparse hair 31 HP:0008070
44 abnormality of cardiovascular system morphology 58 Frequent (79-30%)
45 autistic behavior 31 HP:0000729
46 generalized hypotonia 31 HP:0001290
47 unsteady gait 31 HP:0002317
48 poor speech 31 HP:0002465
49 hypoplastic philtrum 31 HP:0005326

Symptoms via clinical synopsis from OMIM:

56
Head And Neck Eyes:
hypertelorism
strabismus

Head And Neck Head:
macrocephaly
microcephaly

Abdomen Gastrointestinal:
gastroesophageal reflux
constipation
poor feeding
bowel malrotation (in some patients)

Skin Nails Hair Hair:
sparse hair

Skeletal Feet:
flat feet
overlapping toes

Head And Neck Face:
coarse facies
long hypoplastic philtrum

Head And Neck Ears:
preauricular tags

Neurologic Behavioral Psychiatric Manifestations:
autism spectrum disorder
stereotypic behavior
obsessive behavior

Head And Neck Mouth:
gingival hypertrophy

Skeletal:
decreased bone density (in most patients)
exostosis (in some patients)

Laboratory Abnormalities:
decreased heparan sulfate levels in blood and urine

Skeletal Spine:
scoliosis

Neurologic Central Nervous System:
seizures
unsteady gait
delayed psychomotor development
impaired intellectual development
poor or absent speech
more
Genitourinary Internal Genitalia Male:
cryptorchidism

Muscle Soft Tissue:
hypotonia

Skeletal Hands:
fifth finger clinodactyly

Skin Nails Hair Nails:
dysplastic nails

Cardiovascular Heart:
ventricular septal defect (in some patients)
patent ductus arteriosus (in some patients)

Head And Neck Nose:
bulbous nasal tip

Genitourinary Kidneys:
hemolytic-uremic syndrome requiring dialysis (1 patient)

Skin Nails Hair Skin:
sensitive skin

Clinical features from OMIM:

616682

Drugs & Therapeutics for Seizures, Scoliosis, and Macrocephaly/microcephaly Syndrome

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 The Assessment of Cerebral Haemodynamics in Patients With Transient Ischaemic Attack: A Transcranial Doppler Study Recruiting NCT03886129

Search NIH Clinical Center for Seizures, Scoliosis, and Macrocephaly/microcephaly Syndrome

Genetic Tests for Seizures, Scoliosis, and Macrocephaly/microcephaly Syndrome

Genetic tests related to Seizures, Scoliosis, and Macrocephaly/microcephaly Syndrome:

# Genetic test Affiliating Genes
1 Seizures, Scoliosis, and Macrocephaly Syndrome 29 EXT2

Anatomical Context for Seizures, Scoliosis, and Macrocephaly/microcephaly Syndrome

MalaCards organs/tissues related to Seizures, Scoliosis, and Macrocephaly/microcephaly Syndrome:

40
Skin, Bone, Breast, Brain, Kidney, Liver, Spleen

Publications for Seizures, Scoliosis, and Macrocephaly/microcephaly Syndrome

Articles related to Seizures, Scoliosis, and Macrocephaly/microcephaly Syndrome:

(show top 50) (show all 275)
# Title Authors PMID Year
1
Developmental delay, coarse facial features, and epilepsy in a patient with EXT2 gene variants. 56 6
30997052 2019
2
A novel EXT2 mutation in a consanguineous family with severe developmental delay, microcephaly, seizures, feeding difficulties, and osteopenia extends the phenotypic spectrum of autosomal recessive EXT2-related syndrome (AREXT2). 6 56
30075207 2019
3
Novel exostosin-2 missense variants in a family with autosomal recessive exostosin-2-related syndrome: further evidences on the phenotype. 6 56
30288735 2019
4
Old gene, new phenotype: mutations in heparan sulfate synthesis enzyme, EXT2 leads to seizure and developmental disorder, no exostoses. 56 6
26246518 2015
5
New mutations of EXT1 and EXT2 genes in German patients with Multiple Osteochondromas. 6
19344451 2009
6
Mutation screening of the EXT1 and EXT2 genes in patients with hereditary multiple exostoses. 6
9326317 1997
7
Differentiation of suprasellar meningiomas from non-functioning pituitary macroadenomas by 18F-FDG and 13N-Ammonia PET/CT. 61
32552842 2020
8
Spinal pain relief procedures with the assistance of the MRI-updated statistical shape model. 61
31995264 2020
9
Workload Differentiates Breast Surgical Procedures: NSM Associated with Higher Workload Demand than SSM. 61
31916090 2020
10
Integration of cortical thickness data in a statistical shape model of the scapula. 61
32364819 2020
11
Subregional statistical shape modelling identifies lesser trochanter size as a possible risk factor for radiographic hip osteoarthritis, a cross-sectional analysis from the Osteoporotic Fractures in Men Study. 61
32387760 2020
12
Management problems and strategies: The vulnerability of small-sized municipalities. 61
32402043 2020
13
Ultrafast separation of oil/water mixtures with layered double hydroxide coated stainless steel meshes (LDH-SSMs). 61
32473327 2020
14
Improving inference for nonlinear state-space models of animal population dynamics given biased sequential life stage data. 61
32243577 2020
15
Defining the Prognostic Role of MicroRNAs in Cutaneous Melanoma. 61
32275975 2020
16
A Generic Approach to Lung Field Segmentation From Chest Radiographs Using Deep Space and Shape Learning. 61
31425015 2020
17
Measuring the horizontal and vertical growth rates of superficial spreading melanoma: a pilot study with sequential digital dermoscopy. 61
32129054 2020
18
A model of dynamic, within-trial conflict resolution for decision making. 61
32212764 2020
19
Motor development in infancy and spine shape in early old age: Findings from a British birth cohort study. 61
32162719 2020
20
Intrinsic Measures and Shape Analysis of the Intratemporal Facial Nerve. 61
31917770 2020
21
Decomposing Simon task BOLD activation using a drift-diffusion model framework. 61
32127617 2020
22
Predicting real-time traffic conflicts using deep learning. 61
31931409 2020
23
Reconstruction of the lower limb bones from digitised anatomical landmarks using statistical shape modelling. 61
32092603 2020
24
Clinical relevance of augmented statistical shape model of the scapula in the glenoid region. 61
31902570 2020
25
Predicting Knee Joint Instability Using a Tibio-Femoral Statistical Shape Model. 61
32363179 2020
26
Suicide among persons who entered same-sex and opposite-sex marriage in Denmark and Sweden, 1989-2016: a binational, register-based cohort study. 61
31722984 2020
27
Hierarchical self-assembly of a PS-b-P4VP/PS-b-PNIPAM mixture into multicompartment micelles and their response to two-dimensional confinement. 61
31848533 2020
28
"I'll Just Pick It Up…": Women's Acceptability of Self-Sampling Methods for Sexually Transmitted Infection Screening. 61
31688722 2019
29
Medial axis segmentation of cranial nerves using shape statistics-aware discrete deformable models. 61
31236805 2019
30
The "Nipple Whipple"?! A Pilot Study to Assess the Ergonomic Effects of Nipple-Sparing Mastectomy. 61
31342398 2019
31
A novel robust kernel principal component analysis for nonlinear statistical shape modeling from erroneous data. 61
31550670 2019
32
PPR-SSM: personalized PageRank and semantic similarity measures for entity linking. 61
31664891 2019
33
Dual-target hazard perception: Could identifying one hazard hinder a driver's capacity to find a second? 61
31319363 2019
34
Comparative anti-thrombotic activity and haemorrhagic adverse effect of nattokinase and tissue-type plasminogen activator. 61
31695953 2019
35
Differences between pure desmoplastic melanoma and superficial spreading melanoma in terms of survival, distribution and other clinicopathologic features. 61
31237040 2019
36
Typical Shape Differences in the Subtalar Joint Bones Between Subjects with Chronic Ankle Instability and Controls. 61
31042001 2019
37
Assessing right-turning vehicle-pedestrian conflicts at intersections using an integrated microscopic simulation model. 61
31170560 2019
38
Level set distribution model of nested structures using logarithmic transformation. 61
31125739 2019
39
Cholesterol-Induced Conformational Change in the Sphingomyelin Headgroup. 61
31303249 2019
40
Statistical shape-kinematics models of the skeletal joints: Application to the shoulder complex. 61
31946939 2019
41
Multi-factor analysis in language production: Sequential sampling models mimic and extend regression results. 61
31076011 2019
42
Sexual Homicide in France. 61
30829093 2019
43
Lymphatic Endothelial Cells Are Essential Components of the Subcapsular Sinus Macrophage Niche. 61
31053503 2019
44
Posture normalisation of 3D body scans. 61
30777506 2019
45
Artificially enriching the training dataset of statistical shape models via constrained cage-based deformation. 61
31087232 2019
46
Design, synthesis, and cytotoxicity screening of 5-aryl-3-(2-(pyrrolyl) thiophenyl)-1, 2, 4-oxadiazoles as potential antitumor molecules on breast cancer MCF-7 cells. 61
30807934 2019
47
Ischemia time impacts on respiratory chain functions and Ca2+-handling of cardiac subsarcolemmal mitochondria subjected to ischemia reperfusion injury. 61
31088484 2019
48
Why off-the-shelf clavicle plates rarely fit: anatomic analysis of the clavicle through statistical shape modeling. 61
30609957 2019
49
Network screening for large urban road networks: Using GPS data and surrogate measures to model crash frequency and severity. 61
30818096 2019
50
Use of real-world connected vehicle data in identifying high-risk locations based on a new surrogate safety measure. 61
29983165 2019

Variations for Seizures, Scoliosis, and Macrocephaly/microcephaly Syndrome

ClinVar genetic disease variations for Seizures, Scoliosis, and Macrocephaly/microcephaly Syndrome:

6 (show all 13) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 EXT2 NM_000401.3(EXT2):c.1922A>G (p.Tyr641Cys)SNV Pathogenic 638619 11:44255681-44255681 11:44234131-44234131
2 EXT2 NM_000401.3(EXT2):c.613C>T (p.Gln205Ter)SNV Pathogenic 2472 rs121918279 11:44129776-44129776 11:44108226-44108226
3 EXT2 NM_000401.3(EXT2):c.778G>A (p.Asp260Asn)SNV Pathogenic 2474 rs121918280 11:44135787-44135787 11:44114237-44114237
4 EXT2 NM_207122.2(EXT2):c.1173G>A (p.Gln391=)SNV Likely pathogenic 816885 11:44151688-44151688 11:44130138-44130138
5 EXT2 NM_000401.3(EXT2):c.1492C>T (p.Arg498Ter)SNV Conflicting interpretations of pathogenicity 580003 rs772690312 11:44219466-44219466 11:44197916-44197916
6 EXT2 NM_000401.3(EXT2):c.2015C>T (p.Thr672Met)SNV Conflicting interpretations of pathogenicity 134205 rs138722406 11:44255774-44255774 11:44234224-44234224
7 EXT2 NM_000401.3(EXT2):c.359T>G (p.Met120Arg)SNV Conflicting interpretations of pathogenicity 134211 rs140075817 11:44129522-44129522 11:44107972-44107972
8 EXT2 NM_000401.3(EXT2):c.1121C>T (p.Pro374Leu)SNV Conflicting interpretations of pathogenicity 134215 rs141035971 11:44148448-44148448 11:44126898-44126898
9 EXT2 NM_000401.3(EXT2):c.1277G>A (p.Arg426Gln)SNV Conflicting interpretations of pathogenicity 134218 rs138187791 11:44193165-44193165 11:44171615-44171615
10 EXT2 NM_000401.3(EXT2):c.110C>T (p.Ser37Leu)SNV Conflicting interpretations of pathogenicity 304572 rs527624522 11:44129273-44129273 11:44107723-44107723
11 EXT2 NM_000401.3(EXT2):c.1118T>A (p.Val373Asp)SNV Uncertain significance 547989 rs371996957 11:44148445-44148445 11:44126895-44126895
12 EXT2 NM_000401.3(EXT2):c.382C>T (p.Arg128Cys)SNV Uncertain significance 242448 rs376292686 11:44129545-44129545 11:44107995-44107995
13 EXT2 NM_000401.3(EXT2):c.670A>G (p.Met224Val)SNV Uncertain significance 638379 11:44130778-44130778 11:44109228-44109228

UniProtKB/Swiss-Prot genetic disease variations for Seizures, Scoliosis, and Macrocephaly/microcephaly Syndrome:

73
# Symbol AA change Variation ID SNP ID
1 EXT2 p.Met87Arg VAR_076469 rs140075817
2 EXT2 p.Arg95Cys VAR_076470 rs376292686

Expression for Seizures, Scoliosis, and Macrocephaly/microcephaly Syndrome

Search GEO for disease gene expression data for Seizures, Scoliosis, and Macrocephaly/microcephaly Syndrome.

Pathways for Seizures, Scoliosis, and Macrocephaly/microcephaly Syndrome

GO Terms for Seizures, Scoliosis, and Macrocephaly/microcephaly Syndrome

Sources for Seizures, Scoliosis, and Macrocephaly/microcephaly Syndrome

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
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30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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