MCID: RBN017
MIFTS: 37

Robinow Syndrome, Autosomal Dominant 2

Categories: Genetic diseases, Rare diseases, Fetal diseases, Bone diseases, Reproductive diseases

Aliases & Classifications for Robinow Syndrome, Autosomal Dominant 2

MalaCards integrated aliases for Robinow Syndrome, Autosomal Dominant 2:

Name: Robinow Syndrome, Autosomal Dominant 2 53 71 28
Drs2 53 12 71
Autosomal Dominant Robinow Syndrome 2 12 14

Characteristics:

OMIM:

53
Inheritance:
autosomal dominant

Miscellaneous:
onset at birth


HPO:

31
robinow syndrome, autosomal dominant 2:
Onset and clinical course congenital onset
Inheritance autosomal dominant inheritance


Classifications:



Summaries for Robinow Syndrome, Autosomal Dominant 2

OMIM : 53 Robinow syndrome is a skeletal dysplasia characterized by distinctive facial features, including midface hypoplasia, hypertelorism, a short nose, and a broad mouth, known collectively as 'fetal facies.' Additional features include mesomelic dwarfism, macrocephaly, gingival hypertrophy, dental malocclusion, genital hypoplasia, and brachydactyly (summary by Bunn et al., 2015). Additionally, increased skull bone density and appendicular osteosclerosis are present in patients with DRS2 (White et al., 2015; Bunn et al., 2015). For a discussion of genetic heterogeneity of Robinow syndrome, see RRS (268310). (616331)

MalaCards based summary : Robinow Syndrome, Autosomal Dominant 2, is also known as drs2, and has symptoms including macrocephaly, hypertelorism and frontal bossing. An important gene associated with Robinow Syndrome, Autosomal Dominant 2 is DVL1 (Dishevelled Segment Polarity Protein 1), and among its related pathways/superpathways are Endocytosis and Intra-Golgi traffic. The drugs Rivastigmine and Pembrolizumab have been mentioned in the context of this disorder. Affiliated tissues include bone, brain and eye.

Disease Ontology : 12 A Robinow syndrome characterized by autosomal dominant inheritance of mesomelic limb shortening, genital hypoplasia, and distinctive facial features that has material basis in heterozygous mutation in the DVL1 gene on chromosome 1p36.

UniProtKB/Swiss-Prot : 71 Robinow syndrome, autosomal dominant 2: A rare skeletal dysplasia syndrome characterized by dysmorphic features resembling a fetal face, mesomelic limb shortening, hypoplastic external genitalia in males, costovertebral segmentation defects, and renal anomalies.

Related Diseases for Robinow Syndrome, Autosomal Dominant 2

Symptoms & Phenotypes for Robinow Syndrome, Autosomal Dominant 2

Symptoms via clinical synopsis from OMIM:

53
Head And Neck Head:
macrocephaly

Head And Neck Face:
frontal bossing
long philtrum
high forehead
midface hypoplasia
micrognathia (in some patients)

Head And Neck Nose:
short nose
anteverted nares
wide, low nasal bridge

Head And Neck Teeth:
dental crowding
malocclusion
dental anomalies

Genitourinary External Genitalia Male:
micropenis

Growth Height:
short stature (in some patients)

Abdomen External Features:
umbilical hernia (in some patients)

Skeletal:
osteosclerosis (in some patients)

Skeletal Limbs:
mesomelia (in some patients)
undertubulated long bones (in some patients)

Head And Neck Eyes:
hypertelorism
prominent eyes

Skeletal Hands:
clinodactyly
brachydactyly
broad thumbs
hypoplastic distal phalanges

Genitourinary Internal Genitalia Male:
cryptorchidism

Skeletal Feet:
brachydactyly
hypoplastic distal phalanges
broad first toes

Head And Neck Mouth:
triangular mouth
thin upper lip
gingival hyperplasia

Head And Neck Ears:
sensorineural hearing loss (in some patients)
conductive hearing loss (in some patients)
abnormal ear shape (in some patients)
abnormal ear position (in some patients)

Chest RibsSternum Clavicles And Scapulae:
pectus anomalies

Skeletal Skull:
thickened calvaria (in some patients)


Clinical features from OMIM:

616331

Human phenotypes related to Robinow Syndrome, Autosomal Dominant 2:

31 (show all 28)
# Description HPO Frequency HPO Source Accession
1 macrocephaly 31 HP:0000256
2 hypertelorism 31 HP:0000316
3 frontal bossing 31 HP:0002007
4 clinodactyly 31 HP:0030084
5 gingival overgrowth 31 HP:0000212
6 dental malocclusion 31 HP:0000689
7 umbilical hernia 31 occasional (7.5%) HP:0001537
8 thickened calvaria 31 occasional (7.5%) HP:0002684
9 short nose 31 HP:0003196
10 sensorineural hearing impairment 31 occasional (7.5%) HP:0000407
11 anteverted nares 31 HP:0000463
12 short stature 31 occasional (7.5%) HP:0004322
13 broad thumb 31 HP:0011304
14 long philtrum 31 HP:0000343
15 micrognathia 31 occasional (7.5%) HP:0000347
16 cryptorchidism 31 HP:0000028
17 dental crowding 31 HP:0000678
18 conductive hearing impairment 31 occasional (7.5%) HP:0000405
19 brachydactyly 31 HP:0001156
20 thin upper lip vermilion 31 HP:0000219
21 high forehead 31 HP:0000348
22 increased bone mineral density 31 occasional (7.5%) HP:0011001
23 midface retrusion 31 HP:0011800
24 proptosis 31 HP:0000520
25 short distal phalanx of finger 31 HP:0009882
26 micropenis 31 HP:0000054
27 mesomelia 31 occasional (7.5%) HP:0003027
28 triangular mouth 31 HP:0000207

Drugs & Therapeutics for Robinow Syndrome, Autosomal Dominant 2

Drugs for Robinow Syndrome, Autosomal Dominant 2 (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 17)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Rivastigmine Approved, Investigational Phase 3 123441-03-2 77991
2
Pembrolizumab Approved Phase 3 1374853-91-4
3 Cholinergic Agents Phase 3
4 Cholinesterase Inhibitors Phase 3
5 Neuroprotective Agents Phase 3
6 Neurotransmitter Agents Phase 3
7 Protective Agents Phase 3
8 Pharmaceutical Solutions Phase 3
9
Dopamine Approved Phase 2 51-61-6, 62-31-7 681
10
Levodopa Approved Phase 2 59-92-7 6047
11
Pioglitazone Approved, Investigational Phase 2 111025-46-8 4829
12 Dopamine agonists Phase 2
13 Dopamine Agents Phase 2
14 Hypoglycemic Agents Phase 2
15 Nutmeg Approved, Nutraceutical Phase 1
16 Mace Nutraceutical Phase 1
17
Menthol Approved 2216-51-5 16666

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Long-term Safety of Rivastigmine Capsule and Patch in Patients With Mild to Moderately-severe Dementia Associated With Parkinson's Disease (PDD) Completed NCT00623103 Phase 3 Rivastigmine capsule;Rivastigmine transdermal patch
2 Safety and Efficacy Study of Pembrolizumab (MK-3475) as Monotherapy in the Adjuvant Treatment of Renal Cell Carcinoma Post Nephrectomy (MK-3475-564/KEYNOTE-564) Recruiting NCT03142334 Phase 3 Placebo (saline solution)
3 Pioglitazone in Early Parkinson's Disease Completed NCT01280123 Phase 2 Pioglitazone;placebo
4 A Trial to Explore the Potential Benefit of Safinamide on Cognitive Impairment Associated With Parkinson's Disease Completed NCT01211587 Phase 2 safinamide;placebo
5 Nucleus Basalis Deep Brain Stimulation for Thinking & Memory Problems in Parkinson's. Completed NCT01701544 Phase 1, Phase 2
6 Safety and Biomarker Study of EPI-589 in Parkinson's Disease Recruiting NCT02462603 Phase 2 EPI-589
7 Tailored Activity Program-VA Active, not recruiting NCT01357564 Phase 1
8 Deep Brain Stimulation for Patients With Dementia With Lewy Bodies Completed NCT02263937
9 Dissociating Components of Anhedonia: A Pilot fMRI Study Recruiting NCT02569034

Search NIH Clinical Center for Robinow Syndrome, Autosomal Dominant 2

Genetic Tests for Robinow Syndrome, Autosomal Dominant 2

Genetic tests related to Robinow Syndrome, Autosomal Dominant 2:

# Genetic test Affiliating Genes
1 Robinow Syndrome, Autosomal Dominant 2 28 DVL1

Anatomical Context for Robinow Syndrome, Autosomal Dominant 2

MalaCards organs/tissues related to Robinow Syndrome, Autosomal Dominant 2:

38
Bone, Brain, Eye

Publications for Robinow Syndrome, Autosomal Dominant 2

Variations for Robinow Syndrome, Autosomal Dominant 2

ClinVar genetic disease variations for Robinow Syndrome, Autosomal Dominant 2:

6 (show all 17)
# Gene Variation Type Significance SNP ID Assembly Location
1 DVL1 NM_004421.2(DVL1): c.1615delA (p.Ser539Alafs) deletion Pathogenic rs797044837 GRCh37 Chromosome 1, 1273381: 1273381
2 DVL1 NM_004421.2(DVL1): c.1576_1583delCCTGCCTAinsG (p.Pro526Alafs) indel Pathogenic rs797044840 GRCh37 Chromosome 1, 1273413: 1273420
3 DVL1 NM_004421.2(DVL1): c.1570_1571delTTinsC (p.Phe524Profs) indel Pathogenic rs797044833 GRCh37 Chromosome 1, 1273425: 1273426
4 DVL1 NM_004421.2(DVL1): c.1562delC (p.Pro521Hisfs) deletion Pathogenic rs797044839 GRCh37 Chromosome 1, 1273434: 1273434
5 DVL1 NM_004421.2(DVL1): c.1529delG (p.Gly510Valfs) deletion Pathogenic rs797044838 GRCh37 Chromosome 1, 1273467: 1273467
6 DVL1 NM_004421.2(DVL1): c.1519delT (p.Trp507Glyfs) deletion Pathogenic rs797044835 GRCh37 Chromosome 1, 1273477: 1273477
7 DVL1 NM_004421.2(DVL1): c.1505_1517delACCCGGCTGCCCC (p.His502Profs) deletion Pathogenic rs797044834 GRCh37 Chromosome 1, 1273479: 1273491
8 DVL1 NM_004421.2(DVL1): c.1508delC (p.Pro503Argfs) deletion Pathogenic rs797044836 GRCh37 Chromosome 1, 1273488: 1273488
9 DVL1 NM_004421.2(DVL1): c.1522delC (p.Pro508Leufs) deletion Pathogenic rs869025220 GRCh38 Chromosome 1, 1338094: 1338094
10 DVL1 NM_004421.2(DVL1): c.1608_1623del16 (p.Ser537Valfs) deletion Likely pathogenic GRCh38 Chromosome 1, 1337993: 1338008
11 DVL1 NM_004421.2(DVL1): c.1623delG (p.Ser542Valfs) deletion Likely pathogenic GRCh38 Chromosome 1, 1337993: 1337993
12 DVL1 NM_004421.2(DVL1): c.1612_1616dup (p.Ser539Argfs) duplication Likely pathogenic GRCh37 Chromosome 1, 1273380: 1273384
13 DVL1 NM_004421.2(DVL1): c.1496_1508delCGCTGCCCCACCC (p.Pro499Argfs) deletion Likely pathogenic GRCh38 Chromosome 1, 1338108: 1338120
14 DVL3 NM_004423.3(DVL3): c.1617delG (p.Gln539Hisfs) deletion Likely pathogenic GRCh37 Chromosome 3, 183887912: 183887912
15 FZD2 NM_001466.3(FZD2): c.1130G> A (p.Trp377Ter) single nucleotide variant Likely pathogenic GRCh37 Chromosome 17, 42636186: 42636186
16 FZD2 NM_001466.3(FZD2): c.1300G> A (p.Gly434Ser) single nucleotide variant Likely pathogenic GRCh37 Chromosome 17, 42636356: 42636356
17 FZD2 NM_001466.3(FZD2): c.1301_1302delGCinsTT (p.Gly434Val) indel Likely pathogenic GRCh37 Chromosome 17, 42636357: 42636358

Expression for Robinow Syndrome, Autosomal Dominant 2

Search GEO for disease gene expression data for Robinow Syndrome, Autosomal Dominant 2.

Pathways for Robinow Syndrome, Autosomal Dominant 2

Pathways related to Robinow Syndrome, Autosomal Dominant 2 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 11.19 ARF1 SNX3 VPS45
2 10.61 ARF1 VPS45

GO Terms for Robinow Syndrome, Autosomal Dominant 2

Cellular components related to Robinow Syndrome, Autosomal Dominant 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 endosome GO:0005768 9.43 ATP8A2 SNX3 VPS45
2 Golgi membrane GO:0000139 9.33 ARF1 OSBP VPS45
3 Golgi apparatus GO:0005794 9.26 ARF1 ATP8A2 OSBP VPS45
4 clathrin-coated vesicle GO:0030136 8.62 DVL1 SNX3

Biological processes related to Robinow Syndrome, Autosomal Dominant 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 protein transport GO:0015031 9.43 ARF1 SNX3 VPS45
2 transport GO:0006810 9.35 ARF1 ATP8A2 OSBP SNX3 VPS45
3 lipid transport GO:0006869 9.32 ATP8A2 OSBP
4 axonogenesis GO:0007409 9.16 ATP8A2 DVL1
5 positive regulation of neuron projection development GO:0010976 8.8 ATP8A2 DVL1 SNX3

Molecular functions related to Robinow Syndrome, Autosomal Dominant 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 phosphatidylinositol-4-phosphate binding GO:0070273 8.62 OSBP SNX3

Sources for Robinow Syndrome, Autosomal Dominant 2

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
27 GO
28 GTR
29 HGMD
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 MedGen
41 MeSH
42 MESH via Orphanet
43 MGI
45 NCI
46 NCIt
47 NDF-RT
50 NINDS
51 Novoseek
53 OMIM
54 OMIM via Orphanet
58 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
Content
Loading form....