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 57 75 29 6
Drs2 57 12 75
Autosomal Dominant Robinow Syndrome 2 12 15
Robinow Syndrome, Autosomal Dominant, Type 2 40

Characteristics:

OMIM:

57
Inheritance:
autosomal dominant

Miscellaneous:
onset at birth


HPO:

32
robinow syndrome, autosomal dominant 2:
Onset and clinical course congenital onset
Inheritance autosomal dominant inheritance


Classifications:



Summaries for Robinow Syndrome, Autosomal Dominant 2

OMIM : 57 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. 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, and related phenotypes are macrocephaly and hypertelorism

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 : 75 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:

57
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

GenitourinaryInternal GenitaliaMale:
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 Ribs Sternum 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:

32 (show all 28)
# Description HPO Frequency HPO Source Accession
1 macrocephaly 32 HP:0000256
2 hypertelorism 32 HP:0000316
3 frontal bossing 32 HP:0002007
4 clinodactyly 32 HP:0030084
5 gingival overgrowth 32 HP:0000212
6 dental malocclusion 32 HP:0000689
7 umbilical hernia 32 occasional (7.5%) HP:0001537
8 thickened calvaria 32 occasional (7.5%) HP:0002684
9 short nose 32 HP:0003196
10 sensorineural hearing impairment 32 occasional (7.5%) HP:0000407
11 anteverted nares 32 HP:0000463
12 short stature 32 occasional (7.5%) HP:0004322
13 broad thumb 32 HP:0011304
14 long philtrum 32 HP:0000343
15 micrognathia 32 occasional (7.5%) HP:0000347
16 cryptorchidism 32 HP:0000028
17 dental crowding 32 HP:0000678
18 conductive hearing impairment 32 occasional (7.5%) HP:0000405
19 brachydactyly 32 HP:0001156
20 thin upper lip vermilion 32 HP:0000219
21 high forehead 32 HP:0000348
22 increased bone mineral density 32 occasional (7.5%) HP:0011001
23 midface retrusion 32 HP:0011800
24 proptosis 32 HP:0000520
25 short distal phalanx of finger 32 HP:0009882
26 micropenis 32 HP:0000054
27 mesomelia 32 occasional (7.5%) HP:0003027
28 triangular mouth 32 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 26)
# 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
Exenatide Approved, Investigational Phase 2 141758-74-9 15991534
10
Pioglitazone Approved, Investigational Phase 2 111025-46-8 4829
11
Dopamine Approved Phase 2 51-61-6, 62-31-7 681
12
Levodopa Approved Phase 2 59-92-7 6047
13 Hormone Antagonists Phase 2
14 Hormones Phase 2
15 Hormones, Hormone Substitutes, and Hormone Antagonists Phase 2
16 Hypoglycemic Agents Phase 2
17 Incretins Phase 2
18 Dopamine Agents Phase 2
19 Dopamine agonists Phase 2
20 Nutmeg Approved, Nutraceutical Phase 1
21 Mace Nutraceutical Phase 1
22
Ustekinumab Approved, Investigational 815610-63-0
23
Menthol Approved Not Applicable 2216-51-5 16666
24 Dermatologic Agents
25 Interleukin-12
26 Phosphodiesterase 4 Inhibitors

Interventional clinical trials:

(show all 14)
# 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 Florbetapir F 18 PET Imaging of Beta-amyloid in Parkinson's Disease Patients Completed NCT00857532 Phase 2 florbetapir F 18
4 Trial of Exenatide for Parkinson's Disease Completed NCT01971242 Phase 2 Exenatide
5 Pioglitazone in Early Parkinson's Disease Completed NCT01280123 Phase 2 Pioglitazone;placebo
6 A Trial to Explore the Potential Benefit of Safinamide on Cognitive Impairment Associated With Parkinson's Disease Completed NCT01211587 Phase 2 safinamide;placebo
7 Nucleus Basalis Deep Brain Stimulation for Thinking & Memory Problems in Parkinson's. Completed NCT01701544 Phase 1, Phase 2
8 Safety and Biomarker Study of EPI-589 in Parkinson's Disease Recruiting NCT02462603 Phase 2 EPI-589
9 Tailored Activity Program-VA Active, not recruiting NCT01357564 Phase 1
10 Deep Brain Stimulation for Patients With Dementia With Lewy Bodies Completed NCT02263937 Not Applicable
11 Pre-Clinical (Alzheimers) Diagnosis PCD = Optimum Outcomes OO Recruiting NCT02835716 roflumilast
12 Dissociating Components of Anhedonia: A Pilot fMRI Study Active, not recruiting NCT02569034 Not Applicable
13 Multidisciplinary Intervention for Mild Cognitive Impairment Enrolling by invitation NCT02943187 Not Applicable
14 Short-term Cognitive Training in Late-life Depression Terminated NCT01748032 Not Applicable

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 29 DVL1

Anatomical Context for Robinow Syndrome, Autosomal Dominant 2

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

41
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 34)
# 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.1615delA (p.Ser539Alafs) deletion Pathogenic rs797044837 GRCh38 Chromosome 1, 1338001: 1338001
3 DVL1 NM_004421.2(DVL1): c.1576_1583delCCTGCCTAinsG (p.Pro526Alafs) indel Pathogenic rs797044840 GRCh37 Chromosome 1, 1273413: 1273420
4 DVL1 NM_004421.2(DVL1): c.1576_1583delCCTGCCTAinsG (p.Pro526Alafs) indel Pathogenic rs797044840 GRCh38 Chromosome 1, 1338033: 1338040
5 DVL1 NM_004421.2(DVL1): c.1570_1571delTTinsC (p.Phe524Profs) indel Pathogenic rs797044833 GRCh37 Chromosome 1, 1273425: 1273426
6 DVL1 NM_004421.2(DVL1): c.1570_1571delTTinsC (p.Phe524Profs) indel Pathogenic rs797044833 GRCh38 Chromosome 1, 1338045: 1338046
7 DVL1 NM_004421.2(DVL1): c.1562delC (p.Pro521Hisfs) deletion Pathogenic rs797044839 GRCh37 Chromosome 1, 1273434: 1273434
8 DVL1 NM_004421.2(DVL1): c.1562delC (p.Pro521Hisfs) deletion Pathogenic rs797044839 GRCh38 Chromosome 1, 1338054: 1338054
9 DVL1 NM_004421.2(DVL1): c.1529delG (p.Gly510Valfs) deletion Pathogenic rs797044838 GRCh37 Chromosome 1, 1273467: 1273467
10 DVL1 NM_004421.2(DVL1): c.1529delG (p.Gly510Valfs) deletion Pathogenic rs797044838 GRCh38 Chromosome 1, 1338087: 1338087
11 DVL1 NM_004421.2(DVL1): c.1519delT (p.Trp507Glyfs) deletion Pathogenic rs797044835 GRCh37 Chromosome 1, 1273477: 1273477
12 DVL1 NM_004421.2(DVL1): c.1519delT (p.Trp507Glyfs) deletion Pathogenic rs797044835 GRCh38 Chromosome 1, 1338097: 1338097
13 DVL1 NM_004421.2(DVL1): c.1505_1517delACCCGGCTGCCCC (p.His502Profs) deletion Pathogenic rs797044834 GRCh37 Chromosome 1, 1273479: 1273491
14 DVL1 NM_004421.2(DVL1): c.1505_1517delACCCGGCTGCCCC (p.His502Profs) deletion Pathogenic rs797044834 GRCh38 Chromosome 1, 1338099: 1338111
15 DVL1 NM_004421.2(DVL1): c.1508delC (p.Pro503Argfs) deletion Pathogenic rs797044836 GRCh37 Chromosome 1, 1273488: 1273488
16 DVL1 NM_004421.2(DVL1): c.1508delC (p.Pro503Argfs) deletion Pathogenic rs797044836 GRCh38 Chromosome 1, 1338108: 1338108
17 DVL1 NM_004421.2(DVL1): c.1522delC (p.Pro508Leufs) deletion Pathogenic rs869025220 GRCh38 Chromosome 1, 1338094: 1338094
18 DVL1 NM_004421.2(DVL1): c.1522delC (p.Pro508Leufs) deletion Pathogenic rs869025220 GRCh37 Chromosome 1, 1273474: 1273474
19 DVL1 NM_004421.2(DVL1): c.1608_1623del16 (p.Ser537Valfs) deletion Likely pathogenic GRCh38 Chromosome 1, 1337993: 1338008
20 DVL1 NM_004421.2(DVL1): c.1608_1623del16 (p.Ser537Valfs) deletion Likely pathogenic GRCh37 Chromosome 1, 1273373: 1273388
21 DVL1 NM_004421.2(DVL1): c.1623delG (p.Ser542Valfs) deletion Likely pathogenic GRCh38 Chromosome 1, 1337993: 1337993
22 DVL1 NM_004421.2(DVL1): c.1623delG (p.Ser542Valfs) deletion Likely pathogenic GRCh37 Chromosome 1, 1273373: 1273373
23 DVL1 NM_004421.2(DVL1): c.1612_1616dup (p.Ser539Argfs) duplication Likely pathogenic GRCh37 Chromosome 1, 1273380: 1273384
24 DVL1 NM_004421.2(DVL1): c.1612_1616dup (p.Ser539Argfs) duplication Likely pathogenic GRCh38 Chromosome 1, 1338000: 1338004
25 DVL1 NM_004421.2(DVL1): c.1496_1508delCGCTGCCCCACCC (p.Pro499Argfs) deletion Likely pathogenic GRCh38 Chromosome 1, 1338108: 1338120
26 DVL1 NM_004421.2(DVL1): c.1496_1508delCGCTGCCCCACCC (p.Pro499Argfs) deletion Likely pathogenic GRCh37 Chromosome 1, 1273488: 1273500
27 DVL3 NM_004423.3(DVL3): c.1617delG (p.Gln539Hisfs) deletion Likely pathogenic GRCh37 Chromosome 3, 183887912: 183887912
28 DVL3 NM_004423.3(DVL3): c.1617delG (p.Gln539Hisfs) deletion Likely pathogenic GRCh38 Chromosome 3, 184170124: 184170124
29 FZD2 NM_001466.3(FZD2): c.1130G> A (p.Trp377Ter) single nucleotide variant Likely pathogenic GRCh37 Chromosome 17, 42636186: 42636186
30 FZD2 NM_001466.3(FZD2): c.1130G> A (p.Trp377Ter) single nucleotide variant Likely pathogenic GRCh38 Chromosome 17, 44558818: 44558818
31 FZD2 NM_001466.3(FZD2): c.1300G> A (p.Gly434Ser) single nucleotide variant Likely pathogenic GRCh37 Chromosome 17, 42636356: 42636356
32 FZD2 NM_001466.3(FZD2): c.1300G> A (p.Gly434Ser) single nucleotide variant Likely pathogenic GRCh38 Chromosome 17, 44558988: 44558988
33 FZD2 NM_001466.3(FZD2): c.1301_1302delGCinsTT (p.Gly434Val) indel Likely pathogenic GRCh37 Chromosome 17, 42636357: 42636358
34 FZD2 NM_001466.3(FZD2): c.1301_1302delGCinsTT (p.Gly434Val) indel Likely pathogenic GRCh38 Chromosome 17, 44558989: 44558990

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 9.33 ARF1 SNX3 VPS45
2 lipid transport GO:0006869 9.26 ATP8A2 OSBP
3 axonogenesis GO:0007409 8.96 ATP8A2 DVL1
4 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
17 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
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38 LifeMap
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45 MESH via Orphanet
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58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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