SOTOS2
MCID: STS007
MIFTS: 34

Sotos Syndrome 2 (SOTOS2)

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

Aliases & Classifications for Sotos Syndrome 2

MalaCards integrated aliases for Sotos Syndrome 2:

Name: Sotos Syndrome 2 56 58 73 29 13 6 71
Malan Syndrome 56 73
Sotos2 56 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:

56
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 : 56 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)

MalaCards based summary : Sotos Syndrome 2, also known as malan syndrome, 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

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 depressed nasal bridge 58 31 occasional (7.5%) Occasional (29-5%) HP:0005280
18 scoliosis 58 31 occasional (7.5%) Occasional (29-5%) HP:0002650
19 intellectual disability, mild 58 31 occasional (7.5%) Occasional (29-5%) HP:0001256
20 intellectual disability, severe 58 31 occasional (7.5%) Occasional (29-5%) HP:0010864
21 nystagmus 58 31 occasional (7.5%) Occasional (29-5%) HP:0000639
22 frontal bossing 58 31 occasional (7.5%) Occasional (29-5%) HP:0002007
23 narrow mouth 58 31 occasional (7.5%) Occasional (29-5%) HP:0000160
24 high palate 58 31 occasional (7.5%) Occasional (29-5%) HP:0000218
25 anxiety 58 31 occasional (7.5%) Occasional (29-5%) HP:0000739
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 mandibular prognathia 31 HP:0000303
41 delayed speech and language development 31 HP:0000750
42 seizures 58 Occasional (29-5%)
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:

56
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

Drugs & Therapeutics for Sotos Syndrome 2

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Coordination of Rare Diseases at Sanford Recruiting NCT01793168

Search 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. 56 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. 56 6
20673863 2010
3
Malan syndrome (Sotos syndrome 2) in two patients with 19p13.2 deletion encompassing NFIX gene and novel NFIX sequence variant. 56 61
26927468 2016
4
Novel mutations of NFIX gene causing Marshall-Smith syndrome or Sotos-like syndrome: one gene, two phenotypes. 56
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 31) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 NFIX NM_002501.4(NFIX):c.73del (p.Ala25fs)deletion Pathogenic 431130 rs1135401802 19:13135880-13135880 19:13025066-13025066
2 NFIX NC_000019.9:g.(?_13106632)_(13428155_?)deldeletion Pathogenic 473244 19:13106632-13428155
3 NFIX NM_002501.4(NFIX):c.358del (p.Leu120fs)deletion Pathogenic 540464 rs1555696611 19:13136164-13136164 19:13025350-13025350
4 NFIX NC_000019.10:g.(?_13075535)_(13078735_?)deldeletion Pathogenic 583425 19:13186349-13189549 19:13075535-13078735
5 NFIX NM_002501.4(NFIX):c.136A>T (p.Lys46Ter)SNV Pathogenic 620018 rs1568268397 19:13135943-13135943 19:13025129-13025129
6 NFIX NM_002501.4(NFIX):c.43_49dup (p.Glu17fs)duplication Pathogenic 661035 19:13135847-13135848 19:13025033-13025034
7 NFIX NM_002501.4(NFIX):c.232A>T (p.Lys78Ter)SNV Pathogenic 639180 19:13136039-13136039 19:13025225-13025225
8 NFIX NM_002501.4(NFIX):c.303dup (p.Cys102fs)duplication Pathogenic 654601 19:13136104-13136105 19:13025290-13025291
9 NFIX NC_000019.9:g.(?_13186329)_(13189569_?)dupduplication Pathogenic 665055 19:13186329-13189569 19:13075515-13078755
10 NFIX NC_000019.10:g.(?_13087969)_(13094669_?)deldeletion Pathogenic 833187 19:13198783-13205483
11 NFIX NM_002501.4(NFIX):c.568C>T (p.Gln190Ter)SNV Pathogenic 36956 rs387907253 19:13183869-13183869 19:13073055-13073055
12 NFIX NM_002501.4(NFIX):c.179T>C (p.Leu60Pro)SNV Pathogenic 36966 rs387907254 19:13135986-13135986 19:13025172-13025172
13 NFIX NM_002501.4(NFIX):c.362G>C (p.Arg121Pro)SNV Pathogenic 36967 rs387907255 19:13136169-13136169 19:13025355-13025355
14 NFIX NM_002501.4(NFIX):c.716C>G (p.Ser239Ter)SNV Pathogenic 92044 rs587779381 19:13184738-13184738 19:13073924-13073924
15 NFIX NM_002501.4(NFIX):c.60_75dup (p.Phe26fs)duplication Pathogenic 842270 19:13135863-13135864 19:13025049-13025050
16 NFIX NM_002501.4(NFIX):c.338_342dup (p.Arg116fs)duplication Pathogenic 209174 rs797045056 19:13136144-13136145 19:13025330-13025331
17 NFIX NM_002501.4(NFIX):c.955+2T>CSNV Likely pathogenic 581126 rs1568318932 19:13186487-13186487 19:13075673-13075673
18 NFIX NM_002501.4(NFIX):c.337A>G (p.Lys113Glu)SNV Likely pathogenic 559884 rs1555696597 19:13136144-13136144 19:13025330-13025330
19 NFIX NM_002501.4(NFIX):c.467G>C (p.Cys156Ser)SNV Likely pathogenic 496680 rs1555696641 19:13136274-13136274 19:13025460-13025460
20 NFIX NM_002501.4(NFIX):c.143T>C (p.Met48Thr)SNV Uncertain significance 653227 19:13135950-13135950 19:13025136-13025136
21 NFIX NM_002501.4(NFIX):c.988G>A (p.Asp330Asn)SNV Uncertain significance 565825 rs1215112413 19:13189459-13189459 19:13078645-13078645
22 NFIX NM_002501.4(NFIX):c.113G>T (p.Arg38Leu)SNV Uncertain significance 843697 19:13135920-13135920 19:13025106-13025106
23 NFIX NM_002501.4(NFIX):c.1275T>C (p.Pro425=)SNV Uncertain significance 862100 19:13201133-13201133 19:13090319-13090319
24 NFIX NM_002501.4(NFIX):c.183G>A (p.Leu61=)SNV Likely benign 389919 rs369196245 19:13135990-13135990 19:13025176-13025176
25 NFIX NM_002501.4(NFIX):c.600G>A (p.Ala200=)SNV Likely benign 783249 19:13183901-13183901 19:13073087-13073087
26 NFIX NM_002501.4(NFIX):c.1235C>T (p.Ser412Leu)SNV Likely benign 833858 19:13192650-13192650 19:13081836-13081836
27 NFIX NM_002501.4(NFIX):c.117G>A (p.Lys39=)SNV Likely benign 707679 19:13135924-13135924 19:13025110-13025110
28 NFIX NM_002501.4(NFIX):c.1143C>T (p.Ser381=)SNV Likely benign 707572 19:13192558-13192558 19:13081744-13081744
29 NFIX NM_002501.4(NFIX):c.252G>T (p.Arg84=)SNV Likely benign 771267 19:13136059-13136059 19:13025245-13025245
30 NFIX NM_002501.4(NFIX):c.1236G>A (p.Ser412=)SNV Benign 767492 19:13192651-13192651 19:13081837-13081837
31 NFIX NM_002501.4(NFIX):c.1140G>A (p.Ser380=)SNV Benign 198780 rs201174259 19:13192555-13192555 19:13081741-13081741

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

Sources for Sotos Syndrome 2

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68 SNOMED-CT via HPO
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72 UMLS via Orphanet
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