MCID: ARS001
MIFTS: 54

Aarskog-Scott Syndrome

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

Aliases & Classifications for Aarskog-Scott Syndrome

MalaCards integrated aliases for Aarskog-Scott Syndrome:

Name: Aarskog-Scott Syndrome 54 12 24 25 56 71 13
Aarskog Syndrome 12 50 24 25 56 29 52 42 14 69
Faciogenital Dysplasia 12 50 24 25 56 71
Faciodigitogenital Syndrome 50 24 56 71
Aas 25 71
Faciogenital Dysplasia with Attention Deficit-Hyperactivity Disorder 71
Facio-Digito-Genital Dysplasia 25
Aarskog Scott Syndrome 50
Scott Aarskog Syndrome 50
Greig's Syndrome 12
Aarskog Disease 50
Fgdy 50

Characteristics:

Orphanet epidemiological data:

56
aarskog-scott syndrome
Inheritance: Autosomal dominant,Autosomal recessive,X-linked recessive; Prevalence: 1-9/1000000 (Europe); Age of onset: Childhood; Age of death: any age;

OMIM:

54
Miscellaneous:
normal fertility

Inheritance:
x-linked recessive


HPO:

32
aarskog-scott syndrome:
Inheritance x-linked recessive inheritance


Classifications:



Summaries for Aarskog-Scott Syndrome

OMIM : 54
Aarskog-Scott syndrome, also known as faciogenital dysplasia, is an X-linked disorder characterized by short stature, hypertelorism, shawl scrotum, and brachydactyly, although there is wide phenotypic variability and other features, such as joint hyperextensibility, short nose, widow's peak, and inguinal hernia, may also occur. Most patients do not have mental retardation, but some may have neurobehavioral features. Carrier females may present with subtle features, such as widow's peak or short stature (summary by Orrico et al., 2010). (305400)

MalaCards based summary : Aarskog-Scott Syndrome, also known as aarskog syndrome, is related to amyloidosis aa and helsmoortel-van der aa syndrome, and has symptoms including short stature, strabismus and umbilical hernia. An important gene associated with Aarskog-Scott Syndrome is FGD1 (FYVE, RhoGEF And PH Domain Containing 1), and among its related pathways/superpathways are Signaling by Rho GTPases and Actin Nucleation by ARP-WASP Complex. The drugs Neuroserpin and Astragalus have been mentioned in the context of this disorder. Affiliated tissues include heart, skin and endothelial.

NIH Rare Diseases : 50 aarskog syndrome is an inherited disease that affects a person's height, muscles, skeleton, genitals, and appearance of the face. intellectual development may also be affected. about 20 percent of people with aarskog-scott syndrome have mutations in the fgd1 gene. the cause in other affected individuals is unknown. the condition is inherited in an x-linked recessive pattern. last updated: 9/7/2011

UniProtKB/Swiss-Prot : 71 Aarskog-Scott syndrome: A rare multisystemic disorder characterized by disproportionately short stature, and by facial, skeletal and urogenital anomalies. Some patients manifest mental retardation, attention deficit disorder and hyperactivity.

Genetics Home Reference : 25 Aarskog-Scott syndrome is a genetic disorder that affects the development of many parts of the body. This condition mainly affects males, although females may have mild features of the syndrome.

Disease Ontology : 12 A monogenic disease affects a person's height, muscles, skeleton, genitals, and appearance of the face.

Related Diseases for Aarskog-Scott Syndrome

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

(show top 50) (show all 131)
id Related Disease Score Top Affiliating Genes
1 amyloidosis aa 12.2
2 helsmoortel-van der aa syndrome 12.2
3 faciodigitogenital syndrome, autosomal recessive 11.9
4 alopecia areata 11.7
5 adnp syndrome 11.4
6 aplastic anemia 11.1
7 renal nutcracker syndrome 11.0
8 hydrocephalus, sprengel anomaly, and costovertebral dysplasia 10.9
9 superior mesenteric artery syndrome 10.9
10 7q11.23 duplication syndrome 10.9
11 sveinsson chorioretinal atrophy 10.9
12 scott syndrome 10.8
13 williams-beuren region duplication syndrome 10.7
14 adnp-related intellectual disability and autism spectrum disorder 10.7
15 squamous cell carcinoma, head and neck 10.7
16 amyloidosis, hereditary, transthyretin-related 10.7
17 amyloidosis 10.4
18 cerebrovascular disease 10.1
19 arthropathy 10.1
20 polymicrogyria 10.1
21 myopathy 10.1
22 endotheliitis 10.1
23 attention deficit-hyperactivity disorder 10.1
24 unilateral focal polymicrogyria 10.1
25 isolated cerebellar vermis agenesis 10.0 ARHGEF2 FGD1
26 arthritis 9.9
27 al amyloidosis 9.8
28 rheumatoid arthritis 9.8
29 irak4 deficiency 9.8 ARHGEF2 FGD1
30 leukemia 9.7
31 xeroderma pigmentosum, group b 9.7 CDC42 MCF2
32 metatarsus adductus 9.7
33 isolated growth hormone deficiency 9.7
34 spasticity 9.7
35 spastic hemiplegia 9.7
36 hemiplegia 9.7
37 growth hormone deficiency 9.7
38 prostatitis 9.7
39 sarcoma 9.7
40 lymphoma 9.6
41 pulmonary hypertension 9.6
42 cerebritis 9.6
43 alopecia 9.6
44 obesity 9.6
45 crohn's disease 9.6
46 dermatitis 9.6
47 prostate cancer 9.6
48 nephrotic syndrome 9.6
49 atopic dermatitis 9.6
50 thyroiditis 9.6

Graphical network of the top 20 diseases related to Aarskog-Scott Syndrome:



Diseases related to Aarskog-Scott Syndrome

Symptoms & Phenotypes for Aarskog-Scott Syndrome

Symptoms via clinical synopsis from OMIM:

54

Growth- Other:
failure to thrive
delayed puberty
increased upper to lower segment ratio

Head And Neck- Nose:
anteverted nostrils
broad nasal bridge
small, short nose

Head And Neck- Eyes:
strabismus
ptosis
hypertelorism
hyperopia
downward-slanting palpebral fissures

Head And Neck- Mouth:
cleft palate
cleft lip

Genitourinary- Internal Genitalia Male:
cryptorchidism

Neurologic- Central Nervous System:
hyperactivity
attention deficit disorder
mental retardation (one-third)

Chest- Ribs Sternum Clavicles And Scapulae:
pectus excavatum

Head And Neck- Ears:
fleshy earlobes

Growth- Height:
short stature, mild to moderate

Skeletal- Feet:
short broad feet

Skeletal- Spine:
scoliosis
odontoid hypoplasia
cervical spine hypermobility

Skeletal- Hands:
brachydactyly
clinodactyly
short, broad hands
single transverse palmar crease
mild syndactyly
more
Head And Neck- Face:
round face
maxillary hypoplasia
wide philtrum
curved linear dimple below the lower lip

Genitourinary- External Genitalia Male:
shawl scrotum

Abdomen- External Features:
inguinal hernia
prominent umbilicus

Skin Nails & Hair- Hair:
widow's peak

Head And Neck- Teeth:
hypodontia

Skin Nails & Hair- Skin:
single transverse palmar crease

Head And Neck- Neck:
short neck with or without webbing


Clinical features from OMIM:

305400

Human phenotypes related to Aarskog-Scott Syndrome:

56 32 (show top 50) (show all 71)
id Description HPO Frequency Orphanet Frequency HPO Source Accession
1 short stature 56 32 hallmark (90%) Very frequent (99-80%) HP:0004322
2 strabismus 56 32 occasional (7.5%) Occasional (29-5%) HP:0000486
3 umbilical hernia 56 32 hallmark (90%) Very frequent (99-80%) HP:0001537
4 cognitive impairment 56 32 frequent (33%) Frequent (79-30%) HP:0100543
5 ptosis 56 32 frequent (33%) Frequent (79-30%) HP:0000508
6 hypertelorism 56 32 hallmark (90%) Very frequent (99-80%) HP:0000316
7 round face 56 32 occasional (7.5%) Occasional (29-5%) HP:0000311
8 cleft palate 56 32 occasional (7.5%) Occasional (29-5%) HP:0000175
9 megalocornea 56 32 occasional (7.5%) Occasional (29-5%) HP:0000485
10 anteverted nares 56 32 frequent (33%) Frequent (79-30%) HP:0000463
11 shawl scrotum 56 32 hallmark (90%) Very frequent (99-80%) HP:0000049
12 cryptorchidism 56 32 frequent (33%) Frequent (79-30%) HP:0000028
13 short neck 56 32 occasional (7.5%) Occasional (29-5%) HP:0000470
14 broad forehead 56 32 frequent (33%) Frequent (79-30%) HP:0000337
15 inguinal hernia 56 32 frequent (33%) Frequent (79-30%) HP:0000023
16 long philtrum 56 32 frequent (33%) Frequent (79-30%) HP:0000343
17 wide nasal bridge 56 32 frequent (33%) Frequent (79-30%) HP:0000431
18 pectus excavatum 56 32 occasional (7.5%) Occasional (29-5%) HP:0000767
19 finger syndactyly 56 32 frequent (33%) Frequent (79-30%) HP:0006101
20 congestive heart failure 56 32 occasional (7.5%) Occasional (29-5%) HP:0001635
21 downslanted palpebral fissures 56 32 frequent (33%) Frequent (79-30%) HP:0000494
22 low-set, posteriorly rotated ears 56 32 frequent (33%) Frequent (79-30%) HP:0000368
23 pes planus 56 32 occasional (7.5%) Occasional (29-5%) HP:0001763
24 joint hyperflexibility 56 32 frequent (33%) Frequent (79-30%) HP:0005692
25 epicanthus 56 32 occasional (7.5%) Occasional (29-5%) HP:0000286
26 high anterior hairline 56 32 frequent (33%) Frequent (79-30%) HP:0009890
27 talipes 56 32 occasional (7.5%) Occasional (29-5%) HP:0001883
28 single transverse palmar crease 56 32 occasional (7.5%) Occasional (29-5%) HP:0000954
29 hyperextensible skin 56 32 frequent (33%) Frequent (79-30%) HP:0000974
30 genu recurvatum 56 32 occasional (7.5%) Occasional (29-5%) HP:0002816
31 attention deficit hyperactivity disorder 56 32 occasional (7.5%) Occasional (29-5%) HP:0007018
32 delayed eruption of teeth 56 32 occasional (7.5%) Occasional (29-5%) HP:0000684
33 small hand 56 32 hallmark (90%) Very frequent (99-80%) HP:0200055
34 everted lower lip vermilion 56 32 hallmark (90%) Very frequent (99-80%) HP:0000232
35 external ear malformation 56 32 frequent (33%) Frequent (79-30%) HP:0008572
36 short palm 56 32 hallmark (90%) Very frequent (99-80%) HP:0004279
37 short foot 56 32 hallmark (90%) Very frequent (99-80%) HP:0001773
38 clinodactyly of the 5th finger 56 32 frequent (33%) Frequent (79-30%) HP:0004209
39 hypoplasia of the maxilla 56 32 occasional (7.5%) Occasional (29-5%) HP:0000327
40 camptodactyly of finger 56 32 hallmark (90%) Very frequent (99-80%) HP:0100490
41 cleft upper lip 56 32 occasional (7.5%) Occasional (29-5%) HP:0000204
42 broad foot 56 32 hallmark (90%) Very frequent (99-80%) HP:0001769
43 broad palm 56 32 hallmark (90%) Very frequent (99-80%) HP:0001169
44 abnormal vertebral segmentation and fusion 56 32 occasional (7.5%) Occasional (29-5%) HP:0005640
45 failure to thrive 32 HP:0001508
46 scoliosis 32 HP:0002650
47 brachydactyly 32 HP:0001156
48 short nose 32 HP:0003196
49 intellectual disability 32 HP:0001249
50 widow's peak 32 HP:0000349

Drugs & Therapeutics for Aarskog-Scott Syndrome

Drugs for Aarskog-Scott Syndrome (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):


id Name Status Phase Clinical Trials Cas Number PubChem Id
1 Neuroserpin
2 Astragalus Nutraceutical

Interventional clinical trials:


id Name Status NCT ID Phase Drugs
1 Genetic Disease Gene Identification Unknown status NCT00916903

Search NIH Clinical Center for Aarskog-Scott Syndrome

Cochrane evidence based reviews: aarskog syndrome

Genetic Tests for Aarskog-Scott Syndrome

Genetic tests related to Aarskog-Scott Syndrome:

id Genetic test Affiliating Genes
1 Aarskog Syndrome 29 24 FGD1

Anatomical Context for Aarskog-Scott Syndrome

MalaCards organs/tissues related to Aarskog-Scott Syndrome:

39
Heart, Skin, Endothelial

Publications for Aarskog-Scott Syndrome

Articles related to Aarskog-Scott Syndrome:

(show all 33)
id Title Authors Year
1
Novel variant in the FGD1 gene causing Aarskog-Scott syndrome. ( 28587322 )
2017
2
A novel, putatively null, FGD1 variant leading to Aarskog-Scott syndrome in a family from UAE. ( 28103835 )
2017
3
A novel splice site mutation of FGD1 gene in an Aarskog-Scott syndrome patient with a large anterior fontanel. ( 27544718 )
2016
4
A novel FGD1 mutation in a family with Aarskog-Scott syndrome and predominant features of congenital joint contractures. ( 27551683 )
2016
5
Identification of novel mutations in Mexican patients with Aarskog-Scott syndrome. ( 26029706 )
2015
6
Aarskog-Scott syndrome presenting with psychosis: A case study. ( 25911513 )
2015
7
Clinical utility gene card for: Aarskog-Scott Syndrome (faciogenital dysplasia). ( 25227149 )
2014
8
Aarskog-Scott syndrome: a novel mutation in the FGD1 gene associated with severe craniofacial dysplasia. ( 24770546 )
2014
9
Novel FGD1 mutation underlying Aarskog-Scott syndrome with myopathy and distal arthropathy. ( 23211637 )
2013
10
Aarskog-Scott syndrome. ( 23673187 )
2013
11
Exome sequencing identifies a branch point variant in Aarskog-Scott syndrome. ( 23169394 )
2013
12
A novel mutation in a mother and a son with Aarskog-Scott syndrome. ( 23443263 )
2013
13
Mania with Aarskog-Scott syndrome. ( 22565081 )
2012
14
Aarskog-scott syndrome: a review and case report. ( 25206170 )
2012
15
Aarskog-Scott syndrome: first report of a duplication in the FGD1 gene. ( 22211847 )
2012
16
Clinical utility gene card for: Aarskog-Scott syndrome (faciogenital dysplasia). ( 21654724 )
2011
17
The Aarskog-Scott syndrome protein Fgd1 regulates podosome formation and extracellular matrix remodeling in transforming growth factor I^-stimulated aortic endothelial cells. ( 21911474 )
2011
18
Fraternal twins with Aarskog-Scott syndrome due to maternal germline mosaicism. ( 21739585 )
2011
19
Aarskog-Scott syndrome: clinical update and report of nine novel mutations of the FGD1 gene. ( 20082460 )
2010
20
First case of deletion of the faciogenital dysplasia 1 (FGD1) gene in a patient with Aarskog-Scott syndrome. ( 19110080 )
2009
21
Unusually severe expression of craniofacial features in Aarskog-Scott syndrome due to a novel truncating mutation of the FGD1 gene. ( 17152066 )
2007
22
Cerebrovascular disease associated with Aarskog-Scott syndrome. ( 17294235 )
2007
23
Unilateral focal polymicrogyria in a patient with classical Aarskog-Scott syndrome due to a novel missense mutation in an evolutionary conserved RhoGEF domain of the faciogenital dysplasia gene FGD1. ( 17847065 )
2007
24
Neurobehavioral disorders in patients with Aarskog-Scott syndrome affected by novel FGD1 mutations. ( 16688726 )
2006
25
Female counterpart of shawl scrotum in Aarskog-Scott syndrome. ( 16953916 )
2006
26
Attention-deficit/hyperactivity disorder (ADHD) and variable clinical expression of Aarskog-Scott syndrome due to a novel FGD1 gene mutation (R408Q). ( 15809997 )
2005
27
Phenotypic and molecular characterisation of the Aarskog-Scott syndrome: a survey of the clinical variability in light of FGD1 mutation analysis in 46 patients. ( 14560308 )
2004
28
A mutation in the pleckstrin homology (PH) domain of the FGD1 gene in an Italian family with faciogenital dysplasia (Aarskog-Scott syndrome). ( 10930571 )
2000
29
Sperm acrosome defects in a patient with Aarskog-Scott syndrome. ( 8985497 )
1996
30
Isolation and characterization of the faciogenital dysplasia (Aarskog-Scott syndrome) gene: a putative Rho/Rac guanine nucleotide exchange factor. ( 7954831 )
1994
31
Aarskog-Scott syndrome: confirmation of linkage to the pericentromeric region of the X chromosome. ( 7810566 )
1994
32
Aarskog-Scott syndrome of unusual facies, joint hypermobility, genital anomaly and short stature. ( 1227568 )
1975
33
The Aarskog-Scott syndrome in four brothers. ( 1227529 )
1975

Variations for Aarskog-Scott Syndrome

UniProtKB/Swiss-Prot genetic disease variations for Aarskog-Scott Syndrome:

71
id Symbol AA change Variation ID SNP ID
1 FGD1 p.Arg522His VAR_015236 rs137853264
2 FGD1 p.Arg610Gln VAR_015237 rs28935497
3 FGD1 p.Ser205Ile VAR_019268
4 FGD1 p.Glu380Ala VAR_019270
5 FGD1 p.Arg443His VAR_019271

ClinVar genetic disease variations for Aarskog-Scott Syndrome:

6 (show all 19)
id Gene Variation Type Significance SNP ID Assembly Location
1 FGD1 FGD1, 1-BP INS, 2122G insertion Pathogenic
2 FGD1 NM_004463.2(FGD1): c.1829G> A (p.Arg610Gln) single nucleotide variant Pathogenic rs28935497 GRCh37 Chromosome X, 54482666: 54482666
3 FGD1 NM_004463.2(FGD1): c.1565G> A (p.Arg522His) single nucleotide variant Pathogenic rs137853264 GRCh37 Chromosome X, 54491955: 54491955
4 FGD1 FGD1, EX9-12DEL deletion Pathogenic
5 FGD1 FGD1, 1-BP INS, 528C insertion Pathogenic
6 FGD1 NM_004463.2(FGD1): c.1223G> A (p.Arg408Gln) single nucleotide variant Pathogenic rs137853265 GRCh37 Chromosome X, 54494334: 54494334
7 FGD1 FGD1, 1-BP DEL, 2189A deletion Pathogenic
8 FGD1 NM_004463.2(FGD1): c.1328G> T (p.Arg443Leu) single nucleotide variant Pathogenic rs137853266 GRCh37 Chromosome X, 54494229: 54494229
9 FGD1 FGD1, 1-BP INS, 945C insertion Pathogenic
10 FGD1 NM_004463.2(FGD1): c.1396A> G (p.Met466Val) single nucleotide variant Pathogenic rs137853267 GRCh37 Chromosome X, 54492230: 54492230
11 FGD1 NM_004463.2(FGD1): c.1966C> T (p.Arg656Ter) single nucleotide variant Pathogenic rs387906718 GRCh37 Chromosome X, 54481930: 54481930
12 FGD1 NM_004463.2(FGD1): c.1287T> G (p.Tyr429Ter) single nucleotide variant Pathogenic rs398124155 GRCh37 Chromosome X, 54494270: 54494270
13 FGD1 NM_004463.2(FGD1): c.1468C> T (p.Gln490Ter) single nucleotide variant Pathogenic rs398124156 GRCh37 Chromosome X, 54492158: 54492158
14 FGD1 NM_004463.2(FGD1): c.175C> T (p.Gln59Ter) single nucleotide variant Pathogenic rs398124160 GRCh37 Chromosome X, 54521691: 54521691
15 FGD1 NM_004463.2(FGD1): c.2112_2113insTT (p.Asn705Leufs) insertion Pathogenic rs398124161 GRCh37 Chromosome X, 54476127: 54476128
16 FGD1 NM_004463.2(FGD1): c.2135dupC (p.Pro713Thrfs) duplication Pathogenic rs398124162 GRCh37 Chromosome X, 54476105: 54476105
17 FGD1 NM_004463.2(FGD1): c.2016-2A> G single nucleotide variant Pathogenic rs794727099 GRCh37 Chromosome X, 54476736: 54476736
18 FGD1 NM_004463.2(FGD1): c.527dupC (p.Leu177Thrfs) duplication Pathogenic rs756586058 GRCh37 Chromosome X, 54497148: 54497148
19 FGD1 NM_004463.2(FGD1): c.527delC (p.Pro176Hisfs) deletion Pathogenic rs780428919 GRCh38 Chromosome X, 54470715: 54470715

Expression for Aarskog-Scott Syndrome

Search GEO for disease gene expression data for Aarskog-Scott Syndrome.

Pathways for Aarskog-Scott Syndrome

GO Terms for Aarskog-Scott Syndrome

Cellular components related to Aarskog-Scott Syndrome according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 Golgi apparatus GO:0005794 9.56 ARHGEF2 FGD1 FGD3 FGD6
2 lamellipodium GO:0030027 9.33 FGD1 FGD3 FGD6
3 ruffle GO:0001726 9.13 FGD1 FGD3 FGD6
4 cytoskeleton GO:0005856 9.1 ARHGEF2 CDC42 FGD1 FGD3 FGD6 MCF2

Biological processes related to Aarskog-Scott Syndrome according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 positive regulation of GTPase activity GO:0043547 9.72 ARHGEF2 FGD1 FGD3 FGD6 MCF2
2 positive regulation of apoptotic process GO:0043065 9.71 ARHGEF2 FGD1 FGD3 MCF2
3 cytoskeleton organization GO:0007010 9.63 FGD1 FGD3 FGD6
4 regulation of cell shape GO:0008360 9.61 FGD1 FGD3 FGD6
5 actin cytoskeleton organization GO:0030036 9.56 CDC42 FGD1 FGD3 FGD6
6 regulation of small GTPase mediated signal transduction GO:0051056 9.55 ARHGEF2 CDC42 FGD1 FGD3 MCF2
7 regulation of GTPase activity GO:0043087 9.54 FGD1 FGD3 FGD6
8 actin filament organization GO:0007015 9.48 ARHGEF2 CDC42
9 filopodium assembly GO:0046847 9.26 CDC42 FGD1 FGD3 FGD6
10 regulation of Rho protein signal transduction GO:0035023 9.02 ARHGEF2 FGD1 FGD3 FGD6 MCF2

Molecular functions related to Aarskog-Scott Syndrome according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 guanyl-nucleotide exchange factor activity GO:0005085 9.35 ARHGEF2 FGD1 FGD3 FGD6 MCF2
2 small GTPase binding GO:0031267 9.33 FGD1 FGD3 FGD6
3 Rho guanyl-nucleotide exchange factor activity GO:0005089 9.02 ARHGEF2 FGD1 FGD3 FGD6 MCF2

Sources for Aarskog-Scott Syndrome

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7 CNVD
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10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
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33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 MedGen
42 MeSH
43 MESH via Orphanet
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70 UMLS via Orphanet
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