AOS5
MCID: ADM010
MIFTS: 33

Adams-Oliver Syndrome 5 (AOS5)

Categories: Bone diseases, Cardiovascular diseases, Eye diseases, Fetal diseases, Genetic diseases, Immune diseases, Neuronal diseases, Rare diseases, Skin diseases

Aliases & Classifications for Adams-Oliver Syndrome 5

MalaCards integrated aliases for Adams-Oliver Syndrome 5:

Name: Adams-Oliver Syndrome 5 57 72 29 6 70
Aos5 57 72
Adams-Oliver Syndrome, Type 5 39

Characteristics:

OMIM®:

57 (Updated 20-May-2021)
Inheritance:
autosomal dominant

Miscellaneous:
variable phenotype


HPO:

31
adams-oliver syndrome 5:
Inheritance autosomal dominant inheritance


Classifications:



Summaries for Adams-Oliver Syndrome 5

UniProtKB/Swiss-Prot : 72 Adams-Oliver syndrome 5: A form of Adams-Oliver syndrome, a disorder characterized by the congenital absence of skin (aplasia cutis congenita) in combination with transverse limb defects. Aplasia cutis congenita can be located anywhere on the body, but in the vast majority of the cases, it is present on the posterior parietal region where it is often associated with an underlying defect of the parietal bones. Limb abnormalities are typically limb truncation defects affecting the distal phalanges or entire digits (true ectrodactyly). Only rarely, metatarsals/metacarpals or more proximal limb structures are also affected. Apart from transverse limb defects, syndactyly, most commonly of second and third toes, can also be observed. The clinical features are highly variable and can also include cardiovascular malformations, brain abnormalities and vascular defects such as cutis marmorata and dilated scalp veins.

MalaCards based summary : Adams-Oliver Syndrome 5, also known as aos5, is related to adams-oliver syndrome and oliver syndrome. An important gene associated with Adams-Oliver Syndrome 5 is NOTCH1 (Notch Receptor 1). Affiliated tissues include eye, cerebellum and bone, and related phenotypes are splenomegaly and inguinal hernia

OMIM® : 57 Adams-Oliver syndrome (AOS) is a rare developmental disorder defined by the combination of aplasia cutis congenita of the scalp vertex and terminal transverse limb defects (e.g., amputations, syndactyly, brachydactyly, or oligodactyly). In addition, vascular anomalies such as cutis marmorata telangiectatica congenita, pulmonary hypertension, portal hypertension, and retinal hypervascularization are recurrently seen. Congenital heart defects have been estimated to be present in 20% of AOS patients; reported malformations include ventricular septal defects, anomalies of the great arteries and their valves, and tetralogy of Fallot (summary by Stittrich et al., 2014). For a discussion of genetic heterogeneity of Adams-Oliver syndrome, see AOS1 (100300). (616028) (Updated 20-May-2021)

Related Diseases for Adams-Oliver Syndrome 5

Diseases in the Adams-Oliver Syndrome family:

Adams-Oliver Syndrome 1 Adams-Oliver Syndrome 2
Adams-Oliver Syndrome 3 Adams-Oliver Syndrome 4
Adams-Oliver Syndrome 5 Adams-Oliver Syndrome 6

Diseases related to Adams-Oliver Syndrome 5 via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 adams-oliver syndrome 30.8 NOTCH1 MIR4673
2 oliver syndrome 9.5 NOTCH1 MIR4673

Symptoms & Phenotypes for Adams-Oliver Syndrome 5

Human phenotypes related to Adams-Oliver Syndrome 5:

31 (show all 18)
# Description HPO Frequency HPO Source Accession
1 splenomegaly 31 occasional (7.5%) HP:0001744
2 inguinal hernia 31 occasional (7.5%) HP:0000023
3 umbilical hernia 31 occasional (7.5%) HP:0001537
4 hypersplenism 31 occasional (7.5%) HP:0001971
5 esophageal varix 31 occasional (7.5%) HP:0002040
6 aplasia cutis congenita 31 occasional (7.5%) HP:0001057
7 portal vein thrombosis 31 occasional (7.5%) HP:0030242
8 seizure 31 occasional (7.5%) HP:0001250
9 brachydactyly 31 HP:0001156
10 pulmonic stenosis 31 HP:0001642
11 pulmonary arterial hypertension 31 HP:0002092
12 cavernous hemangioma 31 HP:0001048
13 dystrophic toenail 31 HP:0001810
14 syndactyly 31 HP:0001159
15 patent foramen ovale 31 HP:0001655
16 right ventricular hypertrophy 31 HP:0001667
17 right atrial enlargement 31 HP:0030718
18 cutis marmorata telangiectatica congenita 31 HP:0025107

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Skeletal Hands:
brachydactyly

Skin Nails Hair Skin:
cavernous hemangioma
cutis marmorata telangiectatica congenita
strawberry nevi
macular hemangioma

Abdomen External Features:
umbilical hernia (rare)
inguinal hernia (rare)

Head And Neck Head:
aplasia cutis congenita of the scalp
prominent veins of the scalp

Cardiovascular Vascular:
pulmonary artery hypertension
portal vein thrombosis (rare)

Head And Neck Neck:
aplasia cutis congenita (rare)

Skeletal Skull:
absent bone in areas of aplasia cutis congenita

Skeletal Feet:
brachydactyly
syndactyly

Cardiovascular Heart:
right ventricular hypertrophy
pulmonary valve stenosis
tricuspid valve incompetence
mitral valve hypoplasia
multiperforated patent foramen ovale
more
Neurologic Central Nervous System:
seizures (rare)
ischemic infarct of brain
sagittal sinus thrombosis
cortical venous thromboses
structural abnormalities of cerebellum
more
Skin Nails Hair Nails:
dystrophic toenails
hypoplastic or absent toenails

Abdomen Spleen:
splenomegaly (rare)
hypersplenism (rare)

Abdomen Gastrointestinal:
esophageal varices (rare)
hypertensive gastropathy (rare)

Clinical features from OMIM®:

616028 (Updated 20-May-2021)

Drugs & Therapeutics for Adams-Oliver Syndrome 5

Search Clinical Trials , NIH Clinical Center for Adams-Oliver Syndrome 5

Genetic Tests for Adams-Oliver Syndrome 5

Genetic tests related to Adams-Oliver Syndrome 5:

# Genetic test Affiliating Genes
1 Adams-Oliver Syndrome 5 29 NOTCH1

Anatomical Context for Adams-Oliver Syndrome 5

MalaCards organs/tissues related to Adams-Oliver Syndrome 5:

40
Eye, Cerebellum, Bone, Brain

Publications for Adams-Oliver Syndrome 5

Articles related to Adams-Oliver Syndrome 5:

# Title Authors PMID Year
1
Haploinsufficiency of the NOTCH1 Receptor as a Cause of Adams-Oliver Syndrome With Variable Cardiac Anomalies. 57 6
25963545 2015
2
Mutations in NOTCH1 cause Adams-Oliver syndrome. 6 57
25132448 2014
3
Adams-Oliver syndrome and portal hypertension: fortuitous association or common mechanism? 57 6
22307742 2012
4
Familial aplasia cutis congenita and coarctation of the aorta. 6 57
1621771 1992
5
Elucidating the genetic architecture of Adams-Oliver syndrome in a large European cohort. 6
29924900 2018
6
Adams-Oliver syndrome, a family with dominant inheritance and a severe phenotype. 57
21785343 2011
7
De novo copy number variants identify new genes and loci in isolated sporadic tetralogy of Fallot. 6
19597493 2009
8
Notch/gamma-secretase inhibition turns proliferative cells in intestinal crypts and adenomas into goblet cells. 6
15959515 2005

Variations for Adams-Oliver Syndrome 5

ClinVar genetic disease variations for Adams-Oliver Syndrome 5:

6 (show top 50) (show all 954)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 overlap with 5 genes NC_000009.12:g.136545168_136630028del Deletion Pathogenic 161198 GRCh37: 9:139439620-139524480
GRCh38: 9:136545168-136630028
2 NOTCH1 NM_017617.5(NOTCH1):c.4487G>A (p.Cys1496Tyr) SNV Pathogenic 156007 rs587781259 GRCh37: 9:139399861-139399861
GRCh38: 9:136505409-136505409
3 NOTCH1 NM_017617.5(NOTCH1):c.1343G>A (p.Arg448Gln) SNV Pathogenic 219375 rs864622056 GRCh37: 9:139412302-139412302
GRCh38: 9:136517850-136517850
4 NOTCH1 NM_017617.5(NOTCH1):c.4739dup (p.Met1580fs) Duplication Pathogenic 219381 rs864622061 GRCh37: 9:139399403-139399404
GRCh38: 9:136504951-136504952
5 NOTCH1 NM_017617.5(NOTCH1):c.4663G>T (p.Glu1555Ter) SNV Pathogenic 219380 rs746342893 GRCh37: 9:139399480-139399480
GRCh38: 9:136505028-136505028
6 NOTCH1 NM_017617.5(NOTCH1):c.2365C>T (p.Gln789Ter) SNV Pathogenic 544178 rs1554729118 GRCh37: 9:139407575-139407575
GRCh38: 9:136513123-136513123
7 NOTCH1 NM_017617.5(NOTCH1):c.3266G>A (p.Trp1089Ter) SNV Pathogenic 544179 rs1554728428 GRCh37: 9:139402743-139402743
GRCh38: 9:136508291-136508291
8 NOTCH1 NM_017617.5(NOTCH1):c.2380G>T (p.Glu794Ter) SNV Pathogenic 523594 rs1554729113 GRCh37: 9:139407560-139407560
GRCh38: 9:136513108-136513108
9 NOTCH1 NM_017617.5(NOTCH1):c.2704C>T (p.Arg902Cys) SNV Pathogenic 523595 rs1448345366 GRCh37: 9:139405141-139405141
GRCh38: 9:136510689-136510689
10 NOTCH1 NM_017617.5(NOTCH1):c.3281G>A (p.Cys1094Tyr) SNV Pathogenic 523596 rs1554728424 GRCh37: 9:139402728-139402728
GRCh38: 9:136508276-136508276
11 NOTCH1 NM_017617.5(NOTCH1):c.4222G>T (p.Glu1408Ter) SNV Pathogenic 523597 rs587778569 GRCh37: 9:139400126-139400126
GRCh38: 9:136505674-136505674
12 NOTCH1 NM_017617.5(NOTCH1):c.415C>T (p.Gln139Ter) SNV Pathogenic 523583 rs1554730670 GRCh37: 9:139417629-139417629
GRCh38: 9:136523177-136523177
13 NOTCH1 NM_017617.5(NOTCH1):c.794_797delinsCC (p.Asn265fs) Indel Pathogenic 523584 rs1554730184 GRCh37: 9:139413963-139413966
GRCh38: 9:136519511-136519514
14 NOTCH1 NM_017617.5(NOTCH1):c.1933_1934TG[1] (p.Ala646fs) Microsatellite Pathogenic 523585 rs1554729443 GRCh37: 9:139409820-139409821
GRCh38: 9:136515368-136515369
15 NOTCH1 NM_017617.5(NOTCH1):c.4071C>A (p.Cys1357Ter) SNV Pathogenic 566177 rs1564191302 GRCh37: 9:139400277-139400277
GRCh38: 9:136505825-136505825
16 NOTCH1 NM_017617.5(NOTCH1):c.1396del (p.Thr466fs) Deletion Pathogenic 572044 rs1564199476 GRCh37: 9:139412249-139412249
GRCh38: 9:136517797-136517797
17 NOTCH1 NM_017617.5(NOTCH1):c.550C>T (p.Gln184Ter) SNV Pathogenic 645087 rs1589072024 GRCh37: 9:139417494-139417494
GRCh38: 9:136523042-136523042
18 overlap with 17 genes NC_000009.11:g.(?_138683633)_(139440248_?)del Deletion Pathogenic 640461 GRCh37: 9:138683633-139440248
GRCh38:
19 NOTCH1 NM_017617.5(NOTCH1):c.4127del (p.Gly1376fs) Deletion Pathogenic 642523 rs1589058964 GRCh37: 9:139400221-139400221
GRCh38: 9:136505769-136505769
20 NOTCH1 NM_017617.5(NOTCH1):c.1015_1016TG[1] (p.Ala340fs) Microsatellite Pathogenic 845149 GRCh37: 9:139413124-139413125
GRCh38: 9:136518672-136518673
21 NOTCH1 NM_017617.5(NOTCH1):c.2448dup (p.Cys817fs) Duplication Pathogenic 817997 rs1589064285 GRCh37: 9:139407491-139407492
GRCh38: 9:136513039-136513040
22 NOTCH1 NM_017617.5(NOTCH1):c.1649dup (p.Tyr550Ter) Duplication Pathogenic 219378 rs864622059 GRCh37: 9:139410452-139410453
GRCh38: 9:136516000-136516001
23 NOTCH1 NM_017617.5(NOTCH1):c.6049_6050del (p.Ser2017fs) Deletion Pathogenic 219383 rs864622063 GRCh37: 9:139393596-139393597
GRCh38: 9:136499144-136499145
24 NOTCH1 NM_017617.5(NOTCH1):c.743-1G>T SNV Pathogenic/Likely pathogenic 156213 rs587777735 GRCh37: 9:139414018-139414018
GRCh38: 9:136519566-136519566
25 NOTCH1 NM_017617.5(NOTCH1):c.1285T>C (p.Cys429Arg) SNV Pathogenic/Likely pathogenic 156214 rs587777736 GRCh37: 9:139412360-139412360
GRCh38: 9:136517908-136517908
26 NOTCH1 Deletion Likely pathogenic 441283 GRCh37: 9:139439621-139524760
GRCh38:
27 NOTCH1 NM_017617.5(NOTCH1):c.1345T>C (p.Cys449Arg) SNV Likely pathogenic 219376 rs864622057 GRCh37: 9:139412300-139412300
GRCh38: 9:136517848-136517848
28 NOTCH1 NM_017617.5(NOTCH1):c.1367G>A (p.Cys456Tyr) SNV Likely pathogenic 219377 rs864622058 GRCh37: 9:139412278-139412278
GRCh38: 9:136517826-136517826
29 NOTCH1 NM_017617.5(NOTCH1):c.1393G>A (p.Ala465Thr) SNV Likely pathogenic 390565 rs1057523819 GRCh37: 9:139412252-139412252
GRCh38: 9:136517800-136517800
30 NOTCH1 NM_017617.5(NOTCH1):c.4549G>A (p.Asp1517Asn) SNV Likely pathogenic 523598 rs1554727954 GRCh37: 9:139399799-139399799
GRCh38: 9:136505347-136505347
31 NOTCH1 NM_017617.5(NOTCH1):c.4120T>C (p.Cys1374Arg) SNV Likely pathogenic 219379 rs864622060 GRCh37: 9:139400228-139400228
GRCh38: 9:136505776-136505776
32 NOTCH1 NM_017617.5(NOTCH1):c.2153A>G (p.Asn718Ser) SNV Likely pathogenic 1029477 GRCh37: 9:139409016-139409016
GRCh38: 9:136514564-136514564
33 NOTCH1 NC_000009.12:g.(?_136496071)_(136523980_?)del Deletion Likely pathogenic 833155 GRCh37: 9:139390523-139418432
GRCh38:
34 NOTCH1 NM_017617.5(NOTCH1):c.4758_4759insCA (p.Asn1587fs) Insertion Likely pathogenic 973252 GRCh37: 9:139399384-139399385
GRCh38: 9:136504932-136504933
35 NOTCH1 NM_017617.5(NOTCH1):c.1945C>A (p.Pro649Thr) SNV Conflicting interpretations of pathogenicity 802539 rs780710009 GRCh37: 9:139409811-139409811
GRCh38: 9:136515359-136515359
36 NOTCH1 NM_017617.5(NOTCH1):c.6788G>A (p.Arg2263Gln) SNV Conflicting interpretations of pathogenicity 134953 rs200521815 GRCh37: 9:139391403-139391403
GRCh38: 9:136496951-136496951
37 NOTCH1 NM_017617.5(NOTCH1):c.1669+5G>A SNV Conflicting interpretations of pathogenicity 520074 rs771590616 GRCh37: 9:139410428-139410428
GRCh38: 9:136515976-136515976
38 NOTCH1 NM_017617.5(NOTCH1):c.1220C>G (p.Pro407Arg) SNV Conflicting interpretations of pathogenicity 219374 rs754529382 GRCh37: 9:139412624-139412624
GRCh38: 9:136518172-136518172
39 NOTCH1 NM_017617.5(NOTCH1):c.5965G>A (p.Asp1989Asn) SNV Conflicting interpretations of pathogenicity 156212 rs587777734 GRCh37: 9:139393681-139393681
GRCh38: 9:136499229-136499229
40 NOTCH1 NM_017617.5(NOTCH1):c.4067G>A (p.Arg1356His) SNV Uncertain significance 221044 rs864622727 GRCh37: 9:139400281-139400281
GRCh38: 9:136505829-136505829
41 NOTCH1 NM_017617.5(NOTCH1):c.5218G>T (p.Ala1740Ser) SNV Uncertain significance 219382 rs864622062 GRCh37: 9:139396890-139396890
GRCh38: 9:136502438-136502438
42 NOTCH1 NM_017617.5(NOTCH1):c.5605G>T (p.Ala1869Ser) SNV Uncertain significance 241153 rs200603539 GRCh37: 9:139396233-139396233
GRCh38: 9:136501781-136501781
43 NOTCH1 NM_017617.5(NOTCH1):c.6593C>T (p.Ser2198Leu) SNV Uncertain significance 241161 rs761562076 GRCh37: 9:139391598-139391598
GRCh38: 9:136497146-136497146
44 NOTCH1 NM_017617.5(NOTCH1):c.4915G>A (p.Ala1639Thr) SNV Uncertain significance 241144 rs878855026 GRCh37: 9:139399228-139399228
GRCh38: 9:136504776-136504776
45 NOTCH1 NM_017617.5(NOTCH1):c.2951C>T (p.Thr984Met) SNV Uncertain significance 241131 rs769132985 GRCh37: 9:139404203-139404203
GRCh38: 9:136509751-136509751
46 NOTCH1 NM_017617.5(NOTCH1):c.5535_5536delinsAA (p.Gln1846Lys) Indel Uncertain significance 241151 rs878855027 GRCh37: 9:139396302-139396303
GRCh38: 9:136501850-136501851
47 NOTCH1 NM_017617.5(NOTCH1):c.7397C>T (p.Thr2466Met) SNV Uncertain significance 241169 rs369167555 GRCh37: 9:139390794-139390794
GRCh38: 9:136496342-136496342
48 NOTCH1 NM_017617.5(NOTCH1):c.2712C>T (p.Cys904=) SNV Uncertain significance 241128 rs369645726 GRCh37: 9:139405133-139405133
GRCh38: 9:136510681-136510681
49 NOTCH1 NM_017617.5(NOTCH1):c.6376G>A (p.Gly2126Arg) SNV Uncertain significance 241160 rs572960572 GRCh37: 9:139391815-139391815
GRCh38: 9:136497363-136497363
50 NOTCH1 NM_017617.5(NOTCH1):c.7279G>A (p.Gly2427Ser) SNV Uncertain significance 241166 rs370722609 GRCh37: 9:139390912-139390912
GRCh38: 9:136496460-136496460

UniProtKB/Swiss-Prot genetic disease variations for Adams-Oliver Syndrome 5:

72
# Symbol AA change Variation ID SNP ID
1 NOTCH1 p.Cys429Arg VAR_071960 rs587777736
2 NOTCH1 p.Cys1496Tyr VAR_071961 rs587781259
3 NOTCH1 p.Asp1989Asn VAR_071962 rs587777734

Expression for Adams-Oliver Syndrome 5

Search GEO for disease gene expression data for Adams-Oliver Syndrome 5.

Pathways for Adams-Oliver Syndrome 5

GO Terms for Adams-Oliver Syndrome 5

Sources for Adams-Oliver Syndrome 5

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 20-May-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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