SOTOS2
MCID: STS007
MIFTS: 37

Sotos Syndrome 2 (SOTOS2)

Categories: Bone diseases, Eye diseases, Fetal diseases, Genetic diseases, Mental diseases, Rare diseases

Aliases & Classifications for Sotos Syndrome 2

MalaCards integrated aliases for Sotos Syndrome 2:

Name: Sotos Syndrome 2 57 12 58 73 29 13 6 71
Sotos2 57 12 73
Malan Syndrome 57 73
Malan Overgrowth Syndrome 58
Sotos Syndrome, Type 2 39

Characteristics:

Orphanet epidemiological data:

58
malan overgrowth syndrome
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy;

OMIM®:

57 (Updated 05-Mar-2021)
Inheritance:
autosomal dominant


HPO:

31
sotos syndrome 2:
Inheritance autosomal dominant inheritance


Classifications:

Orphanet: 58  
Developmental anomalies during embryogenesis


Summaries for Sotos Syndrome 2

OMIM® : 57 Sotos syndrome-2 (SOTOS2) is clinically characterized by overgrowth, advanced bone age, macrocephaly, and dysmorphic facial features. Patients develop marfanoid habitus, with long and slender body, very low body mass, long narrow face, and arachnodactyly, with age. Impaired intellectual development and behavior anomalies are present (summary by Martinez et al., 2015). For a discussion of genetic heterogeneity of Sotos syndrome, see 117550. (614753) (Updated 05-Mar-2021)

MalaCards based summary : Sotos Syndrome 2, also known as sotos2, is related to marshall-smith syndrome and alacrima, achalasia, and mental retardation syndrome. An important gene associated with Sotos Syndrome 2 is NFIX (Nuclear Factor I X). Affiliated tissues include bone and eye, and related phenotypes are accelerated skeletal maturation and macrocephaly

Disease Ontology : 12 A Sotos syndrome that has material basis in heterozygous mutation in NFIX on chromosome 19p13.

UniProtKB/Swiss-Prot : 73 Sotos syndrome 2: A form of Sotos syndrome, a childhood overgrowth syndrome characterized by prenatal and postnatal overgrowth, developmental delay, mental retardation, advanced bone age, and abnormal craniofacial morphology. SOTOS2 patients have macrocephaly, long narrow face, high forehead, slender habitus, scoliosis, and unusual behavior characterized especially by anxiety.

Related Diseases for Sotos Syndrome 2

Graphical network of the top 20 diseases related to Sotos Syndrome 2:



Diseases related to Sotos Syndrome 2

Symptoms & Phenotypes for Sotos Syndrome 2

Human phenotypes related to Sotos Syndrome 2:

58 31 (show top 50) (show all 53)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 accelerated skeletal maturation 58 31 hallmark (90%) Very frequent (99-80%) HP:0005616
2 macrocephaly 58 31 frequent (33%) Frequent (79-30%) HP:0000256
3 neonatal hypotonia 58 31 frequent (33%) Frequent (79-30%) HP:0001319
4 feeding difficulties in infancy 58 31 frequent (33%) Frequent (79-30%) HP:0008872
5 prominent forehead 58 31 frequent (33%) Frequent (79-30%) HP:0011220
6 strabismus 58 31 frequent (33%) Frequent (79-30%) HP:0000486
7 low posterior hairline 58 31 frequent (33%) Frequent (79-30%) HP:0002162
8 pectus excavatum 58 31 frequent (33%) Frequent (79-30%) HP:0000767
9 slender long bone 58 31 frequent (33%) Frequent (79-30%) HP:0003100
10 narrow face 58 31 frequent (33%) Frequent (79-30%) HP:0000275
11 downslanted palpebral fissures 58 31 frequent (33%) Frequent (79-30%) HP:0000494
12 intellectual disability, moderate 58 31 frequent (33%) Frequent (79-30%) HP:0002342
13 high forehead 58 31 frequent (33%) Frequent (79-30%) HP:0000348
14 tall stature 58 31 frequent (33%) Frequent (79-30%) HP:0000098
15 hypoplasia of the corpus callosum 58 31 frequent (33%) Frequent (79-30%) HP:0002079
16 oval face 58 31 frequent (33%) Frequent (79-30%) HP:0000300
17 frontal bossing 58 31 occasional (7.5%) Occasional (29-5%) HP:0002007
18 scoliosis 58 31 occasional (7.5%) Occasional (29-5%) HP:0002650
19 nystagmus 58 31 occasional (7.5%) Occasional (29-5%) HP:0000639
20 high palate 58 31 occasional (7.5%) Occasional (29-5%) HP:0000218
21 depressed nasal bridge 58 31 occasional (7.5%) Occasional (29-5%) HP:0005280
22 intellectual disability, mild 58 31 occasional (7.5%) Occasional (29-5%) HP:0001256
23 intellectual disability, severe 58 31 occasional (7.5%) Occasional (29-5%) HP:0010864
24 anxiety 58 31 occasional (7.5%) Occasional (29-5%) HP:0000739
25 narrow mouth 58 31 occasional (7.5%) Occasional (29-5%) HP:0000160
26 facial asymmetry 58 31 occasional (7.5%) Occasional (29-5%) HP:0000324
27 deeply set eye 58 31 occasional (7.5%) Occasional (29-5%) HP:0000490
28 pointed chin 58 31 occasional (7.5%) Occasional (29-5%) HP:0000307
29 migraine 58 31 occasional (7.5%) Occasional (29-5%) HP:0002076
30 plagiocephaly 58 31 occasional (7.5%) Occasional (29-5%) HP:0001357
31 optic disc pallor 58 31 occasional (7.5%) Occasional (29-5%) HP:0000543
32 optic disc hypoplasia 58 31 occasional (7.5%) Occasional (29-5%) HP:0007766
33 episodic ataxia 58 31 occasional (7.5%) Occasional (29-5%) HP:0002131
34 hypoplasia of the brainstem 58 31 occasional (7.5%) Occasional (29-5%) HP:0002365
35 scaphocephaly 58 31 occasional (7.5%) Occasional (29-5%) HP:0030799
36 dilation of lateral ventricles 58 31 occasional (7.5%) Occasional (29-5%) HP:0006956
37 seizure 31 occasional (7.5%) HP:0001250
38 ventriculomegaly 58 31 Frequent (79-30%) HP:0002119
39 intellectual disability 31 HP:0001249
40 seizures 58 Occasional (29-5%)
41 mandibular prognathia 31 HP:0000303
42 delayed speech and language development 31 HP:0000750
43 everted lower lip vermilion 31 HP:0000232
44 motor delay 31 HP:0001270
45 long face 31 HP:0000276
46 coxa valga 31 HP:0002673
47 advanced eruption of teeth 31 HP:0006288
48 cutis marmorata 31 HP:0000965
49 astigmatism 31 HP:0000483
50 generalized hypotonia 31 HP:0001290

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Mar-2021)
Head And Neck Head:
macrocephaly
high forehead

Chest External Features:
pectus excavatum

Skeletal Limbs:
coxa valga

Neurologic Central Nervous System:
hypotonia
mental retardation
speech delay
motor retardation
ventricular dilatation
more
Head And Neck Mouth:
small mouth
prognathia
everted lower lip

Growth Height:
birth height above centile 95
postnatal height above centile 98

Growth Other:
height-weight ratio bellow centile 25

Skin Nails Hair Skin:
livedo reticularis, generalized

Neurologic Behavioral Psychiatric Manifestations:
autistic traits
behavioral anomalies

Head And Neck Eyes:
nystagmus
strabismus
astigmatism
hypermetropia
downslanting palpebral fissures

Head And Neck Face:
narrow face
long face

Skeletal Hands:
long fingers

Skeletal:
advanced bone age

Head And Neck Teeth:
premature eruption of teeth

Growth Weight:
birth weight above centile 95

Abdomen External Features:
abdominal wall hypotonia

Skin Nails Hair Nails:
malformed nails

Clinical features from OMIM®:

614753 (Updated 05-Mar-2021)

Drugs & Therapeutics for Sotos Syndrome 2

Search Clinical Trials , NIH Clinical Center for Sotos Syndrome 2

Genetic Tests for Sotos Syndrome 2

Genetic tests related to Sotos Syndrome 2:

# Genetic test Affiliating Genes
1 Sotos Syndrome 2 29 NFIX

Anatomical Context for Sotos Syndrome 2

MalaCards organs/tissues related to Sotos Syndrome 2:

40
Bone, Eye

Publications for Sotos Syndrome 2

Articles related to Sotos Syndrome 2:

# Title Authors PMID Year
1
Missense mutations in the DNA-binding/dimerization domain of NFIX cause Sotos-like features. 57 6
22301465 2012
2
Distinct effects of allelic NFIX mutations on nonsense-mediated mRNA decay engender either a Sotos-like or a Marshall-Smith syndrome. 57 6
20673863 2010
3
Malan syndrome (Sotos syndrome 2) in two patients with 19p13.2 deletion encompassing NFIX gene and novel NFIX sequence variant. 57 61
26927468 2016
4
Novel mutations of NFIX gene causing Marshall-Smith syndrome or Sotos-like syndrome: one gene, two phenotypes. 57
26200704 2015
5
19p13 microduplications encompassing NFIX are responsible for intellectual disability, short stature and small head circumference. 61
29184170 2018
6
An association of 19p13.2 microdeletions with Malan syndrome and Chiari malformation. 61
25736188 2015
7
Sotos syndrome 1 and 2. 61
25345081 2014

Variations for Sotos Syndrome 2

ClinVar genetic disease variations for Sotos Syndrome 2:

6 (show all 40)
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 NFIX NM_002501.4(NFIX):c.179T>C (p.Leu60Pro) SNV Pathogenic 36966 rs387907254 19:13135986-13135986 19:13025172-13025172
2 NFIX NM_002501.4(NFIX):c.362G>C (p.Arg121Pro) SNV Pathogenic 36967 rs387907255 19:13136169-13136169 19:13025355-13025355
3 NFIX NM_002501.4(NFIX):c.73del (p.Ala25fs) Deletion Pathogenic 431130 rs1135401802 19:13135880-13135880 19:13025066-13025066
4 NFIX NM_002501.4(NFIX):c.338_342dup (p.Arg116fs) Duplication Pathogenic 209174 rs797045056 19:13136144-13136145 19:13025330-13025331
5 NFIX NM_002501.4(NFIX):c.716C>G (p.Ser239Ter) SNV Pathogenic 92044 rs587779381 19:13184738-13184738 19:13073924-13073924
6 NFIX NM_001365902.3(NFIX):c.187G>T (p.Glu63Ter) SNV Pathogenic 976042 19:13135994-13135994 19:13025180-13025180
7 NFIX NM_002501.4(NFIX):c.568C>T (p.Gln190Ter) SNV Pathogenic 36956 rs387907253 19:13183869-13183869 19:13073055-13073055
8 LYL1 NC_000019.9:g.(?_13106632)_(13428155_?)del Deletion Pathogenic 473244 19:13106632-13428155
9 NFIX NC_000019.10:g.(?_13075535)_(13078735_?)del Deletion Pathogenic 583425 19:13186349-13189549 19:13075535-13078735
10 NFIX NM_002501.4(NFIX):c.136A>T (p.Lys46Ter) SNV Pathogenic 620018 rs1568268397 19:13135943-13135943 19:13025129-13025129
11 NFIX NM_002501.4(NFIX):c.232A>T (p.Lys78Ter) SNV Pathogenic 639180 rs1599738036 19:13136039-13136039 19:13025225-13025225
12 NFIX NM_002501.4(NFIX):c.303dup (p.Cys102fs) Duplication Pathogenic 654601 rs886041304 19:13136104-13136105 19:13025290-13025291
13 NFIX NM_002501.4(NFIX):c.43_49dup (p.Glu17fs) Duplication Pathogenic 661035 rs1599737421 19:13135847-13135848 19:13025033-13025034
14 NFIX NC_000019.9:g.(?_13186329)_(13189569_?)dup Duplication Pathogenic 665055 19:13186329-13189569 19:13075515-13078755
15 NFIX NM_002501.4(NFIX):c.358del (p.Leu120fs) Deletion Pathogenic 540464 rs1555696611 19:13136164-13136164 19:13025350-13025350
16 NFIX NM_001365902.3(NFIX):c.60_75dup (p.Phe26fs) Duplication Pathogenic 842270 19:13135863-13135864 19:13025049-13025050
17 NFIX NC_000019.10:g.(?_13087969)_(13094669_?)del Deletion Pathogenic 833187 19:13198783-13205483
18 NFIX NM_002501.4(NFIX):c.955+2T>C SNV Likely pathogenic 581126 rs1568318932 19:13186487-13186487 19:13075673-13075673
19 NFIX NM_002501.4(NFIX):c.361C>T (p.Arg121Cys) SNV Likely pathogenic 208724 rs797044911 19:13136168-13136168 19:13025354-13025354
20 NFIX NM_001365902.3(NFIX):c.113G>A (p.Arg38His) SNV Likely pathogenic 976670 19:13135920-13135920 19:13025106-13025106
21 NFIX NM_001365902.3(NFIX):c.220del (p.Arg74fs) Deletion Likely pathogenic 982716 19:13136025-13136025 19:13025211-13025211
22 NFIX NM_002501.4(NFIX):c.467G>C (p.Cys156Ser) SNV Likely pathogenic 496680 rs1555696641 19:13136274-13136274 19:13025460-13025460
23 NFIX NM_002501.4(NFIX):c.143T>A (p.Met48Lys) SNV Likely pathogenic 452926 rs1555696484 19:13135950-13135950 19:13025136-13025136
24 NFIX NM_002501.4(NFIX):c.337A>G (p.Lys113Glu) SNV Likely pathogenic 559884 rs1555696597 19:13136144-13136144 19:13025330-13025330
25 NFIX NM_002501.4(NFIX):c.772del (p.Gln258fs) Deletion Likely pathogenic 928738 19:13184793-13184793 19:13073979-13073979
26 NFIX NM_002501.4(NFIX):c.818+1G>A SNV Likely pathogenic 928739 19:13184841-13184841 19:13074027-13074027
27 NFIX NM_002501.4(NFIX):c.143T>C (p.Met48Thr) SNV Uncertain significance 653227 rs1555696484 19:13135950-13135950 19:13025136-13025136
28 NFIX NM_001365902.3(NFIX):c.113G>T (p.Arg38Leu) SNV Uncertain significance 843697 19:13135920-13135920 19:13025106-13025106
29 NFIX NM_001365902.3(NFIX):c.1423T>C (p.Ser475Pro) SNV Uncertain significance 862100 19:13201133-13201133 19:13090319-13090319
30 NFIX NM_001365902.3(NFIX):c.818+5G>A SNV Uncertain significance 950716 19:13184845-13184845 19:13074031-13074031
31 NFIX NM_001365902.3(NFIX):c.1247C>G (p.Thr416Ser) SNV Uncertain significance 965765 19:13192662-13192662 19:13081848-13081848
32 NFIX NM_002501.4(NFIX):c.988G>A (p.Asp330Asn) SNV Uncertain significance 565825 rs1215112413 19:13189459-13189459 19:13078645-13078645
33 NFIX NM_002501.4(NFIX):c.252G>T (p.Arg84=) SNV Likely benign 771267 rs769513682 19:13136059-13136059 19:13025245-13025245
34 NFIX NM_002501.4(NFIX):c.600G>A (p.Ala200=) SNV Likely benign 783249 rs367591626 19:13183901-13183901 19:13073087-13073087
35 NFIX NM_002501.4(NFIX):c.1143C>T (p.Ser381=) SNV Likely benign 707572 rs777733912 19:13192558-13192558 19:13081744-13081744
36 NFIX NM_002501.4(NFIX):c.117G>A (p.Lys39=) SNV Likely benign 707679 rs148229471 19:13135924-13135924 19:13025110-13025110
37 NFIX NM_001365902.3(NFIX):c.1235C>T (p.Ser412Leu) SNV Likely benign 833858 19:13192650-13192650 19:13081836-13081836
38 NFIX NM_002501.4(NFIX):c.183G>A (p.Leu61=) SNV Likely benign 389919 rs369196245 19:13135990-13135990 19:13025176-13025176
39 NFIX NM_002501.4(NFIX):c.1140G>A (p.Ser380=) SNV Benign 198780 rs201174259 19:13192555-13192555 19:13081741-13081741
40 NFIX NM_002501.4(NFIX):c.1236G>A (p.Ser412=) SNV Benign 767492 rs367955217 19:13192651-13192651 19:13081837-13081837

UniProtKB/Swiss-Prot genetic disease variations for Sotos Syndrome 2:

73
# Symbol AA change Variation ID SNP ID
1 NFIX p.Leu60Pro VAR_068720 rs387907254
2 NFIX p.Arg121Pro VAR_068721 rs387907255
3 NFIX p.Arg38Cys VAR_077571
4 NFIX p.Arg54Pro VAR_077572
5 NFIX p.Arg116Pro VAR_077573
6 NFIX p.Lys125Glu VAR_077574

Expression for Sotos Syndrome 2

Search GEO for disease gene expression data for Sotos Syndrome 2.

Pathways for Sotos Syndrome 2

GO Terms for Sotos Syndrome 2

Cellular components related to Sotos Syndrome 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 chromatin GO:0000785 8.62 NFIX LYL1

Biological processes related to Sotos Syndrome 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 regulation of transcription, DNA-templated GO:0006355 8.62 NFIX LYL1

Molecular functions related to Sotos Syndrome 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 DNA-binding transcription factor activity, RNA polymerase II-specific GO:0000981 8.96 NFIX LYL1
2 RNA polymerase II proximal promoter sequence-specific DNA binding GO:0000978 8.62 NFIX LYL1

Sources for Sotos Syndrome 2

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Mar-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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