Sotos Syndrome 2 disease: Malacards - Research Articles, Drugs, Genes, Clinical Trials

SOTOS2 MCID: STS007 MIFTS: 34	Sotos Syndrome 2 (SOTOS2) Categories: Bone diseases, Eye diseases, Fetal diseases, Genetic diseases, Rare diseases
Genes Variations Tissues Related diseases Publications Symptoms & Phenotypes Expand all tables

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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:

MalaCards categories:
Global: Genetic diseases Fetal diseases Rare diseases
Anatomical: Bone diseases Eye diseases

See all MalaCards categories (disease lists)

ICD10: ³³

Congenital malformations, deformations and chromosomal abnormalities

Other congenital malformations

Other specified congenital malformation syndromes affecting multiple systems

Congenital malformation syndromes involving early overgrowth

Orphanet: ⁵⁸

Developmental anomalies during embryogenesis

External Ids:

OMIM ⁵⁶ 614753

OMIM Phenotypic Series ⁵⁶ PS117550

MeSH ⁴³ D058495

ICD10 via Orphanet ³³ Q87.3

Orphanet ⁵⁸ ORPHA420179

MedGen ⁴¹ C3553660 CN130953

UMLS ⁷¹ C3553660

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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.

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Related Diseases for Sotos Syndrome 2

Diseases in the Sotos Syndrome 1 family:

Sotos Syndrome 2

Sotos Syndrome 3

Diseases related to Sotos Syndrome 2 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 25)

#	Related Disease	Score
1	marshall-smith syndrome	10.4
2	alacrima, achalasia, and mental retardation syndrome	10.4
3	scoliosis	10.2
4	ezh2-related overgrowth	10.2
5	hypotonia	10.2
6	episodic ataxia, type 2	10.0
7	chiari malformation type i	10.0
8	migraine with or without aura 1	10.0
9	pectus excavatum	10.0
10	strabismus	10.0
11	macrocephaly/megalencephaly syndrome, autosomal recessive	10.0
12	weaver syndrome	10.0
13	ataxia and polyneuropathy, adult-onset	10.0
14	aortic aneurysm, familial thoracic 1	10.0
15	global developmental delay, absent or hypoplastic corpus callosum, and dysmorphic facies	10.0
16	familial hemiplegic migraine	10.0
17	aortic aneurysm	10.0
18	learning disability	10.0
19	mechanical strabismus	10.0
20	episodic ataxia	10.0
21	pathologic nystagmus	10.0
22	chiari malformation	10.0
23	megalencephaly	10.0
24	sotos syndrome 1	9.9
25	overgrowth syndrome	9.9

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

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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

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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

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Genetic Tests for Sotos Syndrome 2

Genetic tests related to Sotos Syndrome 2:

#	Genetic test	Affiliating Genes
1	Sotos Syndrome 2 ²⁹	NFIX

Sources

Anatomical Context for Sotos Syndrome 2

MalaCards organs/tissues related to Sotos Syndrome 2:

⁴⁰

Bone, Eye

Sources

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	Yoneda Y...Matsumoto N	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	Malan V...Cormier-Daire V	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	Jezela-Stanek A...Krajewska-Walasek M	26927468	2016
4	Novel mutations of NFIX gene causing Marshall-Smith syndrome or Sotos-like syndrome: one gene, two phenotypes. ⁵⁶	Martinez F...Orellana C	26200704	2015
5	19p13 microduplications encompassing NFIX are responsible for intellectual disability, short stature and small head circumference. ⁶¹	Trimouille A...Moutton S	29184170	2018
6	An association of 19p13.2 microdeletions with Malan syndrome and Chiari malformation. ⁶¹	Shimojima K...Yamamoto T	25736188	2015
7	Sotos syndrome 1 and 2. ⁶¹	Sotos JF	25345081	2014

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Genes for Sotos Syndrome 2

Genes related to Sotos Syndrome 2 (1 elite genes):

- Elite gene

- Cancer Census gene in COSMIC

#	Symbol	Description	Category	Score	Evidence	PubmedIds
1	NFIX	Nuclear Factor I X	Protein Coding	1668.43	Molecular basis known ⁵⁶ Pathogenic ⁶ Causative germline mutation ⁵⁸ Causative variation ⁷³ Genetic Tests ²⁹ GeneCards inferred via : Disorders Variants (show sections)	20673863 22301465

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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_?)del	deletion	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_?)del	deletion	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_?)dup	duplication	Pathogenic	665055		19:13186329-13189569	19:13075515-13078755
10	NFIX	NC_000019.10:g.(?_13087969)_(13094669_?)del	deletion	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>C	SNV	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

Sources

Expression for Sotos Syndrome 2

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

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Pathways for Sotos Syndrome 2

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GO Terms for Sotos Syndrome 2

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Sources for Sotos Syndrome 2

¹ BioSystems

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³ CDC

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⁷ CNVD

⁸ Cochrane Library

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¹⁶ DrugBank

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¹⁸ ExPASy

¹⁹ FMA

²⁰ GeneAnalytics

²¹ GeneCards

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²³ GeneHancer via GeneCards

²⁴ GeneReviews

²⁵ Genetics Home Reference

²⁶ GenomeRNAi

²⁷ GEO DataSets

²⁸ GO

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³¹ HPO

³² ICD10

³³ ICD10 via Orphanet

³⁴ ICD9CM

³⁵ IUPHAR

³⁶ KEGG

³⁷ LifeMap

³⁸ LncRNADisease

³⁹ LOVD

⁴⁰ MalaCards

⁴¹ MedGen

⁴² MedlinePlus

⁴³ MeSH

⁴⁴ MESH via Orphanet

⁴⁵ MGI

⁴⁶ miR2Disease

⁴⁷ NCBI Bookshelf

⁴⁸ NCI

⁴⁹ NCIt

⁵⁰ NDF-RT

⁵¹ NIH Clinical Center

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⁵³ NINDS

⁵⁴ Novoseek

⁵⁵ Novus Biologicals

⁵⁶ OMIM

⁵⁷ OMIM via Orphanet

⁵⁸ Orphanet

⁵⁹ PathCards

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⁶¹ PubMed

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⁶⁷ SNOMED-CT

⁶⁸ SNOMED-CT via HPO

⁶⁹ TGDB

⁷⁰ Tocris

⁷¹ UMLS

⁷² UMLS via Orphanet

⁷³ UniProtKB/Swiss-Prot

⁷⁴ Wikipedia

Sotos Syndrome 2 (SOTOS2)

Aliases & Classifications for Sotos Syndrome 2

MalaCards integrated aliases for Sotos Syndrome 2:

Characteristics:

Orphanet epidemiological data:

OMIM:

HPO:

Classifications:

External Ids:

Summaries for Sotos Syndrome 2

Related Diseases for Sotos Syndrome 2

Diseases in the Sotos Syndrome 1 family:

Diseases related to Sotos Syndrome 2 via text searches within MalaCards or GeneCards Suite gene sharing:

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

Symptoms & Phenotypes for Sotos Syndrome 2

Human phenotypes related to Sotos Syndrome 2:

Symptoms via clinical synopsis from OMIM:

Clinical features from OMIM:

Drugs & Therapeutics for Sotos Syndrome 2

Interventional clinical trials:

Genetic Tests for Sotos Syndrome 2

Genetic tests related to Sotos Syndrome 2:

Anatomical Context for Sotos Syndrome 2

MalaCards organs/tissues related to Sotos Syndrome 2:

Publications for Sotos Syndrome 2

Articles related to Sotos Syndrome 2:

Genes for Sotos Syndrome 2

Genes related to Sotos Syndrome 2 (1 elite genes):

Variations for Sotos Syndrome 2

ClinVar genetic disease variations for Sotos Syndrome 2:

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

Expression for Sotos Syndrome 2

Pathways for Sotos Syndrome 2

GO Terms for Sotos Syndrome 2

Sources for Sotos Syndrome 2