VMLDS1
MCID: VNM003
MIFTS: 40

Van Maldergem Syndrome 1 (VMLDS1)

Categories: Bone diseases, Ear diseases, Fetal diseases, Genetic diseases, Nephrological diseases, Neuronal diseases, Rare diseases, Smell/Taste diseases

Aliases & Classifications for Van Maldergem Syndrome 1

MalaCards integrated aliases for Van Maldergem Syndrome 1:

Name: Van Maldergem Syndrome 1 57 12 74 29 6
Cerebrofacioarticular Syndrome 57 59 74
Vmlds1 57 74
Van Maldergem Wetzburger Verloes Syndrome 72
Cerebro-Facio-Articular Syndrome 74
Van Maldergem Syndrome 59

Characteristics:

Orphanet epidemiological data:

59
cerebrofacioarticular syndrome
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
onset at birth
some features may be variable


HPO:

32
van maldergem syndrome 1:
Inheritance autosomal recessive inheritance
Onset and clinical course congenital onset


Classifications:



External Ids:

Disease Ontology 12 DOID:0080585
UMLS via Orphanet 73 C1832390
Orphanet 59 ORPHA314679
UMLS 72 C1832390

Summaries for Van Maldergem Syndrome 1

OMIM : 57 Van Maldergem syndrome is an autosomal recessive disorder characterized by intellectual disability, typical craniofacial features, auditory malformations resulting in hearing loss, and skeletal and limb malformations. Some patients have renal hypoplasia. Brain MRI typically shows periventricular nodular heterotopia (summary by Cappello et al., 2013). (601390)

MalaCards based summary : Van Maldergem Syndrome 1, also known as cerebrofacioarticular syndrome, is related to van maldergem syndrome and hennekam syndrome. An important gene associated with Van Maldergem Syndrome 1 is DCHS1 (Dachsous Cadherin-Related 1), and among its related pathways/superpathways is Hippo signaling pathway - multiple species. Affiliated tissues include brain, bone and kidney, and related phenotypes are malar flattening and hypertelorism

Disease Ontology : 12 A Van Maldergem syndrome that has material basis in homozygous mutation in the DCHS1 gene on chromosome 11p15.

UniProtKB/Swiss-Prot : 74 Van Maldergem syndrome 1: An autosomal recessive disorder characterized by intellectual disability, typical craniofacial features, auditory malformations resulting in hearing loss, and skeletal and limb malformations. Some patients have renal hypoplasia. Brain MRI typically shows periventricular nodular heterotopia.

Related Diseases for Van Maldergem Syndrome 1

Graphical network of the top 20 diseases related to Van Maldergem Syndrome 1:



Diseases related to Van Maldergem Syndrome 1

Symptoms & Phenotypes for Van Maldergem Syndrome 1

Human phenotypes related to Van Maldergem Syndrome 1:

32 (show all 48)
# Description HPO Frequency HPO Source Accession
1 malar flattening 32 HP:0000272
2 hypertelorism 32 HP:0000316
3 clinodactyly 32 HP:0030084
4 high palate 32 HP:0000218
5 ptosis 32 HP:0000508
6 osteopenia 32 HP:0000938
7 intellectual disability 32 HP:0001249
8 scoliosis 32 HP:0002650
9 dental malocclusion 32 HP:0000689
10 skeletal dysplasia 32 HP:0002652
11 wide nasal bridge 32 HP:0000431
12 microtia 32 HP:0008551
13 sensorineural hearing impairment 32 HP:0000407
14 micrognathia 32 HP:0000347
15 narrow forehead 32 HP:0000341
16 sacral dimple 32 HP:0000960
17 generalized hypotonia 32 HP:0001290
18 tented upper lip vermilion 32 HP:0010804
19 feeding difficulties 32 HP:0011968
20 narrow chest 32 HP:0000774
21 epicanthus 32 HP:0000286
22 growth delay 32 HP:0001510
23 short 4th metacarpal 32 HP:0010044
24 joint laxity 32 HP:0001388
25 talipes equinovarus 32 HP:0001762
26 hypospadias 32 HP:0000047
27 hypoplasia of the maxilla 32 HP:0000327
28 conductive hearing impairment 32 HP:0000405
29 anal atresia 32 HP:0002023
30 downturned corners of mouth 32 HP:0002714
31 renal hypoplasia 32 HP:0000089
32 blepharophimosis 32 HP:0000581
33 midface retrusion 32 HP:0011800
34 wide anterior fontanel 32 HP:0000260
35 tracheomalacia 32 HP:0002779
36 cutaneous finger syndactyly 32 HP:0010554
37 anteriorly placed anus 32 HP:0001545
38 atresia of the external auditory canal 32 HP:0000413
39 pachygyria 32 HP:0001302
40 hypoplasia of the corpus callosum 32 HP:0002079
41 short clavicles 32 HP:0000894
42 short palpebral fissure 32 HP:0012745
43 irregular dentition 32 HP:0040079
44 short fourth metatarsal 32 HP:0004689
45 wide cranial sutures 32 HP:0010537
46 simplified gyral pattern 32 HP:0009879
47 subcortical band heterotopia 32 HP:0032409
48 periventricular nodular heterotopia 32 HP:0032388

Symptoms via clinical synopsis from OMIM:

57
Head And Neck Eyes:
hypertelorism
ptosis
epicanthal folds
short palpebral fissures

Skeletal:
osteopenia
skeletal dysplasia
joint laxity

Skeletal Spine:
scoliosis

Head And Neck Ears:
microtia
hearing loss, conductive
hearing loss, sensorineural
atresia of the external auditory canals

Skin Nails Hair Skin:
sacral dimple

Genitourinary External Genitalia Male:
hypospadias

Chest Ribs Sternum Clavicles And Scapulae:
short clavicles

Head And Neck Nose:
broad nasal bridge
thickening of the nasal alae

Head And Neck Mouth:
high-arched palate
downturned mouth
tented upper lip
thick gums

Chest External Features:
narrow thorax

Head And Neck Head:
large anterior fontanels

Respiratory Airways:
tracheomalacia (tracheostomy may be required)

Skeletal Hands:
clinodactyly
syndactyly, cutaneous
hand deformities
short fourth metacarpals
flexion of the pip joints
more
Neurologic Central Nervous System:
intellectual disability
pachygyria
simplified gyral pattern
subcortical band heterotopia
periventricular nodular heterotopia
more
Head And Neck Teeth:
dental malocclusion
irregular dentition

Head And Neck Face:
micrognathia
flat midface
maxillary hypoplasia
bitemporal narrowing

Skeletal Feet:
talipes equinovarus
foot deformities
short fourth metatarsals

Abdomen Gastrointestinal:
anal atresia
anteriorly placed anus
poor feeding

Skeletal Skull:
wide cranial sutures
thickened skull base
thickened frontal bones

Muscle Soft Tissue:
hypotonia

Genitourinary Kidneys:
hypoplastic kidneys

Growth Other:
poor growth

Respiratory:
respiratory difficulties due to tracheomalacia

Skeletal Limbs:
subluxation of the radial heads

Clinical features from OMIM:

601390

MGI Mouse Phenotypes related to Van Maldergem Syndrome 1:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 hearing/vestibular/ear MP:0005377 8.62 DCHS1 FAT4

Drugs & Therapeutics for Van Maldergem Syndrome 1

Search Clinical Trials , NIH Clinical Center for Van Maldergem Syndrome 1

Genetic Tests for Van Maldergem Syndrome 1

Genetic tests related to Van Maldergem Syndrome 1:

# Genetic test Affiliating Genes
1 Van Maldergem Syndrome 1 29 DCHS1

Anatomical Context for Van Maldergem Syndrome 1

MalaCards organs/tissues related to Van Maldergem Syndrome 1:

41
Brain, Bone, Kidney, Breast

Publications for Van Maldergem Syndrome 1

Articles related to Van Maldergem Syndrome 1:

(show all 20)
# Title Authors PMID Year
1
Van Maldergem syndrome: further characterisation and evidence for neuronal migration abnormalities and autosomal recessive inheritance. 38 8 71
22473091 2012
2
Mutations in genes encoding the cadherin receptor-ligand pair DCHS1 and FAT4 disrupt cerebral cortical development. 8 71
24056717 2013
3
Hennekam syndrome can be caused by FAT4 mutations and be allelic to Van Maldergem syndrome. 38 71
24913602 2014
4
A further patient with van Maldergem syndrome. 38 71
22469822 2012
5
Cerebro-facio-articular syndrome of Van Maldergem: confirmation of a new MR/MCA syndrome. 8
8026105 1994
6
Mental retardation with blepharo-naso-facial abnormalities and hand malformations: a new syndrome? 8
1633641 1992
7
Autosomal recessive intestinal lymphangiectasia and lymphedema, with facial anomalies and mental retardation. 71
2624276 1989
8
Intestinal lymphangiectasia-A novel finding in Van Maldergem syndrome challenging the role of lymphedema for the distinction from Hennekam syndrome. 38
31063239 2019
9
Dchs1-Fat4 regulation of osteogenic differentiation in mouse. 38
31358536 2019
10
Coexistence of genetic conditions: exploring a possible relationship. 38
31384091 2019
11
Van Maldergem syndrome and Hennekam syndrome: Further delineation of allelic phenotypes. 38
29681106 2018
12
A newborn diagnosed with van Maldergem syndrome. 38
29505454 2018
13
Whole-Exome Sequencing Reveals FAT4 Mutations in a Clinically Unrecognizable Patient with Syndromic CAKUT: A Case Report. 38
28878612 2017
14
Neuron-specific knockdown of the Drosophila fat induces reduction of life span, deficient locomotive ability, shortening of motoneuron terminal branches and defects in axonal targeting. 38
28488382 2017
15
Middle ear abnormalities in Van Maldergem syndrome. 38
27739185 2017
16
A patient with van Maldergem syndrome with endocrine abnormalities, hypogonadotropic hypogonadism, and breast aplasia/hypoplasia. 38
29046692 2017
17
Mammalian cadherins DCHS1-FAT4 affect functional cerebral architecture. 38
25930014 2016
18
Dachsous1b cadherin regulates actin and microtubule cytoskeleton during early zebrafish embryogenesis. 38
26160902 2015
19
Original Solution for Middle Ear Implant and Anesthetic/Surgical Management in a Child with Severe Craniofacial Dysmorphism. 38
26491591 2015
20
Regulation of neuronal migration by Dchs1-Fat4 planar cell polarity. 38
24998526 2014

Variations for Van Maldergem Syndrome 1

ClinVar genetic disease variations for Van Maldergem Syndrome 1:

6
# Gene Variation Type Significance SNP ID GRCh37 Pos GRCh38 Pos
1 DCHS1 NM_003737.4(DCHS1): c.2382G> C (p.Gln794His) single nucleotide variant Pathogenic rs369091875 11:6654716-6654716 11:6633485-6633485
2 DCHS1 NM_003737.4(DCHS1): c.2503G> T (p.Gly835Ter) single nucleotide variant Pathogenic rs483352917 11:6654240-6654240 11:6633009-6633009
3 DCHS1 NM_003737.4(DCHS1): c.2543del (p.Thr848fs) deletion Pathogenic rs483352918 11:6654200-6654200 11:6632969-6632969
4 DCHS1 NM_003737.4(DCHS1): c.7109A> T (p.Asn2370Ile) single nucleotide variant Pathogenic rs483352919 11:6646466-6646466 11:6625235-6625235
5 DCHS1 NM_003737.4(DCHS1): c.5821A> G (p.Ser1941Gly) single nucleotide variant Uncertain significance 11:6648449-6648449 11:6627218-6627218
6 DCHS1 NM_003737.4(DCHS1): c.4114G> A (p.Gly1372Ser) single nucleotide variant Likely benign rs869312675 11:6651911-6651911 11:6630680-6630680
7 DCHS1 NM_003737.4(DCHS1): c.3158G> C (p.Trp1053Ser) single nucleotide variant Likely benign rs138340204 11:6653585-6653585 11:6632354-6632354

UniProtKB/Swiss-Prot genetic disease variations for Van Maldergem Syndrome 1:

74
# Symbol AA change Variation ID SNP ID
1 DCHS1 p.Asn2370Ile VAR_070928 rs483352919

Expression for Van Maldergem Syndrome 1

Search GEO for disease gene expression data for Van Maldergem Syndrome 1.

Pathways for Van Maldergem Syndrome 1

Pathways related to Van Maldergem Syndrome 1 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 10.09 FAT4 DCHS1

GO Terms for Van Maldergem Syndrome 1

Cellular components related to Van Maldergem Syndrome 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 apical part of cell GO:0045177 8.62 FAT4 DCHS1

Biological processes related to Van Maldergem Syndrome 1 according to GeneCards Suite gene sharing:

(show all 12)
# Name GO ID Score Top Affiliating Genes
1 cell adhesion GO:0007155 9.51 FAT4 DCHS1
2 homophilic cell adhesion via plasma membrane adhesion molecules GO:0007156 9.49 FAT4 DCHS1
3 kidney development GO:0001822 9.48 FAT4 DCHS1
4 neurogenesis GO:0022008 9.46 FAT4 DCHS1
5 heart morphogenesis GO:0003007 9.43 FAT4 DCHS1
6 heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules GO:0007157 9.4 FAT4 DCHS1
7 branching involved in ureteric bud morphogenesis GO:0001658 9.37 FAT4 DCHS1
8 digestive tract development GO:0048565 9.32 FAT4 DCHS1
9 hippo signaling GO:0035329 9.26 FAT4 DCHS1
10 ossification involved in bone maturation GO:0043931 9.16 FAT4 DCHS1
11 nephron development GO:0072006 8.96 FAT4 DCHS1
12 condensed mesenchymal cell proliferation GO:0072137 8.62 FAT4 DCHS1

Molecular functions related to Van Maldergem Syndrome 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 calcium ion binding GO:0005509 8.62 FAT4 DCHS1

Sources for Van Maldergem Syndrome 1

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 TGDB
71 Tocris
72 UMLS
73 UMLS via Orphanet
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