AOS5
MCID: ADM010
MIFTS: 34

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 56 73 29 6 71
Aos5 56 73
Adams-Oliver Syndrome, Type 5 39

Characteristics:

OMIM:

56
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 : 73 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 bone, brain and heart, and related phenotypes are seizures and inguinal hernia

OMIM : 56 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)

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 31.0 NOTCH1 MIR4673
2 oliver syndrome 9.2 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 seizures 31 occasional (7.5%) HP:0001250
2 inguinal hernia 31 occasional (7.5%) HP:0000023
3 splenomegaly 31 occasional (7.5%) HP:0001744
4 umbilical hernia 31 occasional (7.5%) HP:0001537
5 hypersplenism 31 occasional (7.5%) HP:0001971
6 esophageal varix 31 occasional (7.5%) HP:0002040
7 aplasia cutis congenita 31 occasional (7.5%) HP:0001057
8 portal vein thrombosis 31 occasional (7.5%) HP:0030242
9 brachydactyly 31 HP:0001156
10 pulmonary arterial hypertension 31 HP:0002092
11 cavernous hemangioma 31 HP:0001048
12 patent foramen ovale 31 HP:0001655
13 pulmonic stenosis 31 HP:0001642
14 dystrophic toenail 31 HP:0001810
15 syndactyly 31 HP:0001159
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:

56
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

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

Anatomical Context for Adams-Oliver Syndrome 5

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

40
Bone, Brain, Heart, Skin, Cerebellum

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. 6 56
25963545 2015
2
Mutations in NOTCH1 cause Adams-Oliver syndrome. 56 6
25132448 2014
3
Adams-Oliver syndrome and portal hypertension: fortuitous association or common mechanism? 56 6
22307742 2012
4
Familial aplasia cutis congenita and coarctation of the aorta. 6 56
1621771 1992
5
Adams-Oliver Syndrome 6
27077170 2016
6
Adams-Oliver syndrome, a family with dominant inheritance and a severe phenotype. 56
21785343 2011
7
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 626) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 NOTCH1 NM_017617.5(NOTCH1):c.4487G>A (p.Cys1496Tyr)SNV Pathogenic 156007 rs587781259 9:139399861-139399861 9:136505409-136505409
2 NOTCH1 NOTCH1, 85-KB DELdeletion Pathogenic 161198 9:139439620-139524480 9:136545168-136630028
3 NOTCH1 NM_017617.5(NOTCH1):c.6049_6050del (p.Ser2017fs)deletion Pathogenic 219383 rs864622063 9:139393596-139393597 9:136499144-136499145
4 NOTCH1 NM_017617.5(NOTCH1):c.4739dup (p.Met1580fs)duplication Pathogenic 219381 rs864622061 9:139399404-139399404 9:136504952-136504952
5 NOTCH1 NM_017617.5(NOTCH1):c.4663G>T (p.Glu1555Ter)SNV Pathogenic 219380 rs746342893 9:139399480-139399480 9:136505028-136505028
6 NOTCH1 NM_017617.5(NOTCH1):c.1649dup (p.Tyr550Ter)duplication Pathogenic 219378 rs864622059 9:139410453-139410453 9:136516001-136516001
7 NOTCH1 NM_017617.5(NOTCH1):c.1343G>A (p.Arg448Gln)SNV Pathogenic 219375 rs864622056 9:139412302-139412302 9:136517850-136517850
8 NOTCH1 NM_017617.5(NOTCH1):c.794_797delinsCC (p.Asn265fs)indel Pathogenic 523584 rs1554730184 9:139413963-139413966 9:136519511-136519514
9 NOTCH1 NM_017617.5(NOTCH1):c.415C>T (p.Gln139Ter)SNV Pathogenic 523583 rs1554730670 9:139417629-139417629 9:136523177-136523177
10 NOTCH1 NM_017617.5(NOTCH1):c.4222G>T (p.Glu1408Ter)SNV Pathogenic 523597 rs587778569 9:139400126-139400126 9:136505674-136505674
11 NOTCH1 NM_017617.5(NOTCH1):c.3281G>A (p.Cys1094Tyr)SNV Pathogenic 523596 rs1554728424 9:139402728-139402728 9:136508276-136508276
12 NOTCH1 NM_017617.5(NOTCH1):c.2704C>T (p.Arg902Cys)SNV Pathogenic 523595 rs1448345366 9:139405141-139405141 9:136510689-136510689
13 NOTCH1 NM_017617.5(NOTCH1):c.2380G>T (p.Glu794Ter)SNV Pathogenic 523594 rs1554729113 9:139407560-139407560 9:136513108-136513108
14 NOTCH1 NM_017617.5(NOTCH1):c.1933_1934TG[1] (p.Ala646fs)short repeat Pathogenic 523585 rs1554729443 9:139409820-139409821 9:136515368-136515369
15 NOTCH1 NM_017617.5(NOTCH1):c.2365C>T (p.Gln789Ter)SNV Pathogenic 544178 rs1554729118 9:139407575-139407575 9:136513123-136513123
16 NOTCH1 NM_017617.5(NOTCH1):c.1396del (p.Thr466fs)deletion Pathogenic 572044 rs1564199476 9:139412249-139412249 9:136517797-136517797
17 NOTCH1 NM_017617.5(NOTCH1):c.4071C>A (p.Cys1357Ter)SNV Pathogenic 566177 rs1564191302 9:139400277-139400277 9:136505825-136505825
18 NOTCH1 NM_017617.5(NOTCH1):c.4127del (p.Gly1376fs)deletion Pathogenic 642523 9:139400221-139400221 9:136505771-136505771
19 NOTCH1 NM_017617.5(NOTCH1):c.3266G>A (p.Trp1089Ter)SNV Pathogenic 544179 rs1554728428 9:139402743-139402743 9:136508291-136508291
20 NOTCH1 NM_017617.5(NOTCH1):c.550C>T (p.Gln184Ter)SNV Pathogenic 645087 9:139417494-139417494 9:136523042-136523042
21 covers 17 genes, none of which curated to show dosage sensitivity NC_000009.11:g.(?_138683633)_(139440248_?)deldeletion Pathogenic 640461 9:138683633-139440248
22 NOTCH1 NM_017617.5(NOTCH1):c.743-1G>TSNV Pathogenic/Likely pathogenic 156213 rs587777735 9:139414018-139414018 9:136519566-136519566
23 NOTCH1 NM_017617.5(NOTCH1):c.1285T>C (p.Cys429Arg)SNV Pathogenic/Likely pathogenic 156214 rs587777736 9:139412360-139412360 9:136517908-136517908
24 NOTCH1 NM_017617.5(NOTCH1):c.1367G>A (p.Cys456Tyr)SNV Likely pathogenic 219377 rs864622058 9:139412278-139412278 9:136517826-136517826
25 NOTCH1 NM_017617.5(NOTCH1):c.1345T>C (p.Cys449Arg)SNV Likely pathogenic 219376 rs864622057 9:139412300-139412300 9:136517848-136517848
26 NOTCH1 NM_017617.5(NOTCH1):c.4120T>C (p.Cys1374Arg)SNV Likely pathogenic 219379 rs864622060 9:139400228-139400228 9:136505776-136505776
27 NOTCH1 deletion Likely pathogenic 441283 9:139439621-139524760
28 NOTCH1 NM_017617.5(NOTCH1):c.1393G>A (p.Ala465Thr)SNV Likely pathogenic 390565 rs1057523819 9:139412252-139412252 9:136517800-136517800
29 NOTCH1 NM_017617.5(NOTCH1):c.4549G>A (p.Asp1517Asn)SNV Likely pathogenic 523598 rs1554727954 9:139399799-139399799 9:136505347-136505347
30 NOTCH1 NM_017617.5(NOTCH1):c.1669+5G>ASNV Conflicting interpretations of pathogenicity 520074 rs771590616 9:139410428-139410428 9:136515976-136515976
31 NOTCH1 NM_017617.5(NOTCH1):c.5223G>A (p.Ala1741=)SNV Conflicting interpretations of pathogenicity 508856 rs766444406 9:139396885-139396885 9:136502433-136502433
32 NOTCH1 NM_017617.5(NOTCH1):c.6836C>T (p.Ala2279Val)SNV Conflicting interpretations of pathogenicity 450491 rs200370953 9:139391355-139391355 9:136496903-136496903
33 NOTCH1 NM_017617.5(NOTCH1):c.5934+8G>ASNV Conflicting interpretations of pathogenicity 477954 rs747822127 9:139394996-139394996 9:136500544-136500544
34 NOTCH1 NM_017617.5(NOTCH1):c.5168-4G>ASNV Conflicting interpretations of pathogenicity 477939 rs751709616 9:139396944-139396944 9:136502492-136502492
35 NOTCH1 NM_017617.5(NOTCH1):c.1100-7T>CSNV Conflicting interpretations of pathogenicity 477872 rs376603720 9:139412751-139412751 9:136518299-136518299
36 NOTCH1 NM_017617.5(NOTCH1):c.147C>T (p.Gly49=)SNV Conflicting interpretations of pathogenicity 477876 rs746002433 9:139418425-139418425 9:136523973-136523973
37 NOTCH1 NM_017617.5(NOTCH1):c.7606G>A (p.Val2536Ile)SNV Conflicting interpretations of pathogenicity 477975 rs111627256 9:139390585-139390585 9:136496133-136496133
38 NOTCH1 NM_017617.5(NOTCH1):c.2352C>T (p.Ser784=)SNV Conflicting interpretations of pathogenicity 477897 rs774701000 9:139407845-139407845 9:136513393-136513393
39 NOTCH1 NM_017617.5(NOTCH1):c.3860G>A (p.Arg1287His)SNV Conflicting interpretations of pathogenicity 561319 9:139401209-139401209 9:136506757-136506757
40 NOTCH1 NM_017617.5(NOTCH1):c.4930C>T (p.Leu1644=)SNV Conflicting interpretations of pathogenicity 390445 rs568700183 9:139399213-139399213 9:136504761-136504761
41 NOTCH1 NM_017617.5(NOTCH1):c.5506G>A (p.Asp1836Asn)SNV Conflicting interpretations of pathogenicity 415395 rs200100726 9:139396332-139396332 9:136501880-136501880
42 NOTCH1 NM_017617.5(NOTCH1):c.1553C>T (p.Thr518Met)SNV Conflicting interpretations of pathogenicity 373661 rs377535397 9:139411726-139411726 9:136517274-136517274
43 NOTCH1 NM_017617.5(NOTCH1):c.3528C>T (p.His1176=)SNV Conflicting interpretations of pathogenicity 289720 rs202133782 9:139401872-139401872 9:136507420-136507420
44 NOTCH1 NM_017617.5(NOTCH1):c.2354-5T>CSNV Conflicting interpretations of pathogenicity 390031 rs371944522 9:139407591-139407591 9:136513139-136513139
45 NOTCH1 NM_017617.5(NOTCH1):c.339C>T (p.Asn113=)SNV Conflicting interpretations of pathogenicity 415416 rs369947231 9:139418233-139418233 9:136523781-136523781
46 NOTCH1 NM_017617.5(NOTCH1):c.999C>T (p.Ser333=)SNV Conflicting interpretations of pathogenicity 409051 rs751646144 9:139413143-139413143 9:136518691-136518691
47 NOTCH1 NM_017617.5(NOTCH1):c.4031C>T (p.Thr1344Met)SNV Conflicting interpretations of pathogenicity 449810 rs201215245 9:139400317-139400317 9:136505865-136505865
48 NOTCH1 NM_017617.5(NOTCH1):c.3249C>T (p.Cys1083=)SNV Conflicting interpretations of pathogenicity 415413 rs139994842 9:139402760-139402760 9:136508308-136508308
49 NOTCH1 NM_017617.5(NOTCH1):c.6291G>A (p.Pro2097=)SNV Conflicting interpretations of pathogenicity 415427 rs201987555 9:139391900-139391900 9:136497448-136497448
50 NOTCH1 NM_017617.5(NOTCH1):c.6227C>T (p.Thr2076Ile)SNV Conflicting interpretations of pathogenicity 409056 rs1022510242 9:139391964-139391964 9:136497512-136497512

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

73
# 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
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
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
Content
Loading form....