AOS6
MCID: ADM012
MIFTS: 26

Adams-Oliver Syndrome 6 (AOS6)

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 6

MalaCards integrated aliases for Adams-Oliver Syndrome 6:

Name: Adams-Oliver Syndrome 6 56 73 29 6
Aos6 56 73

Characteristics:

OMIM:

56
Inheritance:
autosomal dominant

Miscellaneous:
marked intrafamilial variability of clinical features
incomplete penetrance in some families


HPO:

31
adams-oliver syndrome 6:
Inheritance autosomal dominant inheritance


Classifications:



Summaries for Adams-Oliver Syndrome 6

UniProtKB/Swiss-Prot : 73 Adams-Oliver syndrome 6: 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 6, is also known as aos6. An important gene associated with Adams-Oliver Syndrome 6 is DLL4 (Delta Like Canonical Notch Ligand 4). Affiliated tissues include bone, skin and brain, and related phenotypes are portal hypertension and hypoplastic toenails

OMIM : 56 Adams-Oliver syndrome 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 recurrent findings. 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). (616589)

Related Diseases for Adams-Oliver Syndrome 6

Symptoms & Phenotypes for Adams-Oliver Syndrome 6

Human phenotypes related to Adams-Oliver Syndrome 6:

31 (show all 14)
# Description HPO Frequency HPO Source Accession
1 portal hypertension 31 occasional (7.5%) HP:0001409
2 hypoplastic toenails 31 occasional (7.5%) HP:0001800
3 hepatic fibrosis 31 occasional (7.5%) HP:0001395
4 renal hypoplasia 31 occasional (7.5%) HP:0000089
5 esophageal varix 31 occasional (7.5%) HP:0002040
6 cutis marmorata 31 occasional (7.5%) HP:0000965
7 brachydactyly 31 HP:0001156
8 ventricular septal defect 31 HP:0001629
9 truncus arteriosus 31 HP:0001660
10 aplasia cutis congenita of scalp 31 HP:0007385
11 tricuspid regurgitation 31 HP:0005180
12 syndactyly 31 HP:0001159
13 foot oligodactyly 31 HP:0001849
14 calvarial skull defect 31 HP:0001362

Symptoms via clinical synopsis from OMIM:

56
Skeletal Hands:
brachydactyly
symphalangism

Cardiovascular Heart:
ventricular septal defect
tricuspid insufficiency

Abdomen Liver:
hepatic fibrosis (rare)
portal hypertension (rare)

Abdomen Gastrointestinal:
esophageal varices (rare)

Abdomen Spleen:
congenital splenomegaly (rare)

Skeletal Skull:
skull defect (underlying aplasia cutis congenita)

Skeletal Feet:
brachydactyly
syndactyly
missing toes
brachysyndactyly
symbrachydactyly

Cardiovascular Vascular:
truncus arteriosus

Skin Nails Hair Skin:
cutis marmorata (in some patients)
scalp defect (aplasia cutis congenita)
bald area on scalp (in some patients)

Head And Neck Head:
aplasia congenita cutis of the scalp vertex

Genitourinary Kidneys:
small kidneys (rare)

Skin Nails Hair Nails:
hypoplastic toenails (in some patients)

Clinical features from OMIM:

616589

Drugs & Therapeutics for Adams-Oliver Syndrome 6

Search Clinical Trials , NIH Clinical Center for Adams-Oliver Syndrome 6

Genetic Tests for Adams-Oliver Syndrome 6

Genetic tests related to Adams-Oliver Syndrome 6:

# Genetic test Affiliating Genes
1 Adams-Oliver Syndrome 6 29 DLL4

Anatomical Context for Adams-Oliver Syndrome 6

MalaCards organs/tissues related to Adams-Oliver Syndrome 6:

40
Bone, Skin, Brain, Heart, Kidney, Eye

Publications for Adams-Oliver Syndrome 6

Articles related to Adams-Oliver Syndrome 6:

# Title Authors PMID Year
1
Heterozygous Loss-of-Function Mutations in DLL4 Cause Adams-Oliver Syndrome. 56 6
26299364 2015
2
Adams-Oliver Syndrome 6
27077170 2016
3
Mutations in NOTCH1 cause Adams-Oliver syndrome. 56
25132448 2014

Variations for Adams-Oliver Syndrome 6

ClinVar genetic disease variations for Adams-Oliver Syndrome 6:

6 (show all 14) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 DLL4 NM_019074.4(DLL4):c.1168T>C (p.Cys390Arg)SNV Pathogenic 204372 rs796065347 15:41227243-41227243 15:40935045-40935045
2 DLL4 NM_019074.4(DLL4):c.1169G>A (p.Cys390Tyr)SNV Pathogenic 204371 rs796065346 15:41227244-41227244 15:40935046-40935046
3 DLL4 NM_019074.4(DLL4):c.1660C>T (p.Gln554Ter)SNV Pathogenic 204368 rs796065344 15:41228845-41228845 15:40936647-40936647
4 DLL4 NM_019074.4(DLL4):c.1672C>T (p.Arg558Ter)SNV Pathogenic 204369 rs61750844 15:41228857-41228857 15:40936659-40936659
5 DLL4 NM_019074.4(DLL4):c.361G>C (p.Ala121Pro)SNV Pathogenic 204375 rs796065350 15:41222847-41222847 15:40930649-40930649
6 DLL4 NM_019074.4(DLL4):c.556C>T (p.Arg186Cys)SNV Pathogenic 204373 rs796065348 15:41223862-41223862 15:40931664-40931664
7 DLL4 NM_019074.4(DLL4):c.1310G>C (p.Cys437Ser)SNV Pathogenic 523591 rs1555393125 15:41228495-41228495 15:40936297-40936297
8 DLL4 NM_019074.4(DLL4):c.1397G>A (p.Cys466Tyr)SNV Pathogenic 523592 rs1247027543 15:41228582-41228582 15:40936384-40936384
9 DLL4 NM_019074.4(DLL4):c.1825C>T (p.Gln609Ter)SNV Pathogenic 523582 rs1555393182 15:41229010-41229010 15:40936812-40936812
10 DLL4 NM_019074.4(DLL4):c.1392C>A (p.Cys464Ter)SNV Likely pathogenic 800940 15:41228577-41228577 15:40936379-40936379
11 DLL4 NM_019074.4(DLL4):c.949A>C (p.Thr317Pro)SNV Likely pathogenic 523590 rs1555393027 15:41226844-41226844 15:40934646-40934646
12 DLL4 NM_019074.4(DLL4):c.799C>A (p.Pro267Thr)SNV Conflicting interpretations of pathogenicity 204374 rs796065349 15:41224594-41224594 15:40932396-40932396
13 DLL4 NM_019074.4(DLL4):c.1240+5G>CSNV Uncertain significance 523605 rs1555393082 15:41227320-41227320 15:40935122-40935122
14 DLL4 NM_019074.4(DLL4):c.265_267del (p.Phe89del)deletion Uncertain significance 523604 rs1555392837 15:41222242-41222244 15:40930044-40930046

UniProtKB/Swiss-Prot genetic disease variations for Adams-Oliver Syndrome 6:

73
# Symbol AA change Variation ID SNP ID
1 DLL4 p.Ala121Pro VAR_075858 rs796065350
2 DLL4 p.Arg186Cys VAR_075859 rs796065348
3 DLL4 p.Phe195Leu VAR_075860 rs796065351
4 DLL4 p.Pro267Thr VAR_075861 rs796065349
5 DLL4 p.Cys390Arg VAR_075862 rs796065347
6 DLL4 p.Cys390Tyr VAR_075863 rs796065346
7 DLL4 p.Cys455Trp VAR_075864 rs796065345

Expression for Adams-Oliver Syndrome 6

Search GEO for disease gene expression data for Adams-Oliver Syndrome 6.

Pathways for Adams-Oliver Syndrome 6

GO Terms for Adams-Oliver Syndrome 6

Sources for Adams-Oliver Syndrome 6

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
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