VMLDS1
MCID: VNM003
MIFTS: 42

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 56 12 73 29 6
Cerebrofacioarticular Syndrome 56 58 73
Vmlds1 56 73
Van Maldergem Wetzburger Verloes Syndrome 71
Cerebro-Facio-Articular Syndrome 73
Van Maldergem Syndrome 58

Characteristics:

Orphanet epidemiological data:

58
cerebrofacioarticular syndrome
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM:

56
Inheritance:
autosomal recessive

Miscellaneous:
onset at birth
some features may be variable


HPO:

31
van maldergem syndrome 1:
Inheritance autosomal recessive inheritance
Onset and clinical course congenital onset


Classifications:

Orphanet: 58  
Rare neurological diseases
Developmental anomalies during embryogenesis


Summaries for Van Maldergem Syndrome 1

OMIM : 56 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 heart, and related phenotypes are global developmental delay and abnormal facial shape

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

UniProtKB/Swiss-Prot : 73 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:

58 31 (show top 50) (show all 77)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 global developmental delay 58 31 hallmark (90%) Very frequent (99-80%) HP:0001263
2 abnormal facial shape 58 31 hallmark (90%) Very frequent (99-80%) HP:0001999
3 microtia 58 31 hallmark (90%) Very frequent (99-80%) HP:0008551
4 infantile muscular hypotonia 58 31 hallmark (90%) Very frequent (99-80%) HP:0008947
5 camptodactyly 58 31 hallmark (90%) Very frequent (99-80%) HP:0012385
6 osteopenia 58 31 frequent (33%) Frequent (79-30%) HP:0000938
7 micrognathia 58 31 frequent (33%) Frequent (79-30%) HP:0000347
8 intellectual disability, moderate 58 31 frequent (33%) Frequent (79-30%) HP:0002342
9 conductive hearing impairment 58 31 frequent (33%) Frequent (79-30%) HP:0000405
10 renal hypoplasia 58 31 frequent (33%) Frequent (79-30%) HP:0000089
11 large fontanelles 58 31 frequent (33%) Frequent (79-30%) HP:0000239
12 gastrostomy tube feeding in infancy 58 31 frequent (33%) Frequent (79-30%) HP:0011471
13 syndactyly 58 31 frequent (33%) Frequent (79-30%) HP:0001159
14 hypertelorism 58 31 occasional (7.5%) Occasional (29-5%) HP:0000316
15 agenesis of corpus callosum 58 31 occasional (7.5%) Occasional (29-5%) HP:0001274
16 ataxia 58 31 occasional (7.5%) Occasional (29-5%) HP:0001251
17 self-injurious behavior 58 31 occasional (7.5%) Occasional (29-5%) HP:0100716
18 wide nasal bridge 58 31 occasional (7.5%) Occasional (29-5%) HP:0000431
19 short stature 58 31 occasional (7.5%) Occasional (29-5%) HP:0004322
20 microcephaly 58 31 occasional (7.5%) Occasional (29-5%) HP:0000252
21 intellectual disability, severe 58 31 occasional (7.5%) Occasional (29-5%) HP:0010864
22 epicanthus 58 31 occasional (7.5%) Occasional (29-5%) HP:0000286
23 narrow mouth 58 31 occasional (7.5%) Occasional (29-5%) HP:0000160
24 lymphedema 58 31 occasional (7.5%) Occasional (29-5%) HP:0001004
25 ventriculomegaly 58 31 occasional (7.5%) Occasional (29-5%) HP:0002119
26 talipes equinovarus 58 31 occasional (7.5%) Occasional (29-5%) HP:0001762
27 hypospadias 58 31 occasional (7.5%) Occasional (29-5%) HP:0000047
28 cerebellar vermis hypoplasia 58 31 occasional (7.5%) Occasional (29-5%) HP:0001320
29 hypoplasia of the maxilla 58 31 occasional (7.5%) Occasional (29-5%) HP:0000327
30 abnormal heart morphology 58 31 occasional (7.5%) Occasional (29-5%) HP:0001627
31 blepharophimosis 58 31 occasional (7.5%) Occasional (29-5%) HP:0000581
32 pulmonic stenosis 58 31 occasional (7.5%) Occasional (29-5%) HP:0001642
33 hypoplasia of the corpus callosum 58 31 occasional (7.5%) Occasional (29-5%) HP:0002079
34 tracheomalacia 58 31 occasional (7.5%) Occasional (29-5%) HP:0002779
35 anteriorly placed anus 58 31 occasional (7.5%) Occasional (29-5%) HP:0001545
36 anal stenosis 58 31 occasional (7.5%) Occasional (29-5%) HP:0002025
37 dysplastic corpus callosum 58 31 occasional (7.5%) Occasional (29-5%) HP:0006989
38 irregular dentition 58 31 occasional (7.5%) Occasional (29-5%) HP:0040079
39 absence of pubertal development 58 31 occasional (7.5%) Occasional (29-5%) HP:0008197
40 caudal appendage 58 31 occasional (7.5%) Occasional (29-5%) HP:0002825
41 bilateral choanal atresia/stenosis 58 31 occasional (7.5%) Occasional (29-5%) HP:0200138
42 gray matter heterotopia 31 occasional (7.5%) HP:0002282
43 malar flattening 31 HP:0000272
44 clinodactyly 31 HP:0030084
45 intellectual disability 31 HP:0001249
46 scoliosis 31 HP:0002650
47 ptosis 31 HP:0000508
48 high palate 31 HP:0000218
49 skeletal dysplasia 31 HP:0002652
50 dental malocclusion 31 HP:0000689

Symptoms via clinical synopsis from OMIM:

56
Head And Neck Eyes:
hypertelorism
ptosis
epicanthal folds
short palpebral fissures

Neurologic Central Nervous System:
intellectual disability
pachygyria
simplified gyral pattern
subcortical band heterotopia
periventricular nodular heterotopia
more
Skeletal:
osteopenia
skeletal dysplasia
joint laxity

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
Skeletal Spine:
scoliosis

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

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

26 (show all 20)
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased shRNA abundance (Z-score < -2) GR00366-A-10 9.65 DCHS1
2 Decreased shRNA abundance (Z-score < -2) GR00366-A-109 9.65 DCHS1 FAT4
3 Decreased shRNA abundance (Z-score < -2) GR00366-A-111 9.65 DCHS1
4 Decreased shRNA abundance (Z-score < -2) GR00366-A-153 9.65 DCHS1
5 Decreased shRNA abundance (Z-score < -2) GR00366-A-213 9.65 FAT4
6 Decreased shRNA abundance (Z-score < -2) GR00366-A-27 9.65 DCHS1
7 Decreased shRNA abundance (Z-score < -2) GR00366-A-28 9.65 FAT4
8 Decreased shRNA abundance (Z-score < -2) GR00366-A-61 9.65 FAT4
9 Decreased shRNA abundance (Z-score < -2) GR00366-A-68 9.65 FAT4
10 Increased shRNA abundance (Z-score > 2) GR00366-A-114 9.4 DCHS1
11 Increased shRNA abundance (Z-score > 2) GR00366-A-140 9.4 DCHS1
12 Increased shRNA abundance (Z-score > 2) GR00366-A-151 9.4 DCHS1 FAT4
13 Increased shRNA abundance (Z-score > 2) GR00366-A-161 9.4 FAT4
14 Increased shRNA abundance (Z-score > 2) GR00366-A-180 9.4 DCHS1
15 Increased shRNA abundance (Z-score > 2) GR00366-A-190 9.4 FAT4
16 Increased shRNA abundance (Z-score > 2) GR00366-A-208 9.4 FAT4
17 Increased shRNA abundance (Z-score > 2) GR00366-A-214 9.4 DCHS1
18 Increased shRNA abundance (Z-score > 2) GR00366-A-30 9.4 FAT4
19 Increased shRNA abundance (Z-score > 2) GR00366-A-42 9.4 FAT4
20 Increased shRNA abundance (Z-score > 2) GR00366-A-83 9.4 DCHS1

MGI Mouse Phenotypes related to Van Maldergem Syndrome 1:

45
# 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

Anatomical Context for Van Maldergem Syndrome 1

MalaCards organs/tissues related to Van Maldergem Syndrome 1:

40
Brain, Bone, Heart, Kidney, Trachea, 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. 61 56 6
22473091 2012
2
Mutations in genes encoding the cadherin receptor-ligand pair DCHS1 and FAT4 disrupt cerebral cortical development. 56 6
24056717 2013
3
Hennekam syndrome can be caused by FAT4 mutations and be allelic to Van Maldergem syndrome. 61 6
24913602 2014
4
A further patient with van Maldergem syndrome. 61 6
22469822 2012
5
Cerebro-facio-articular syndrome of Van Maldergem: confirmation of a new MR/MCA syndrome. 56
8026105 1994
6
Mental retardation with blepharo-naso-facial abnormalities and hand malformations: a new syndrome? 56
1633641 1992
7
Autosomal recessive intestinal lymphangiectasia and lymphedema, with facial anomalies and mental retardation. 6
2624276 1989
8
Dchs1-Fat4 regulation of osteogenic differentiation in mouse. 61
31358536 2019
9
Intestinal lymphangiectasia-A novel finding in Van Maldergem syndrome challenging the role of lymphedema for the distinction from Hennekam syndrome. 61
31063239 2019
10
Coexistence of genetic conditions: exploring a possible relationship. 61
31384091 2019
11
Van Maldergem syndrome and Hennekam syndrome: Further delineation of allelic phenotypes. 61
29681106 2018
12
A newborn diagnosed with van Maldergem syndrome. 61
29505454 2018
13
Whole-Exome Sequencing Reveals FAT4 Mutations in a Clinically Unrecognizable Patient with Syndromic CAKUT: A Case Report. 61
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. 61
28488382 2017
15
Middle ear abnormalities in Van Maldergem syndrome. 61
27739185 2017
16
A patient with van Maldergem syndrome with endocrine abnormalities, hypogonadotropic hypogonadism, and breast aplasia/hypoplasia. 61
29046692 2017
17
Mammalian cadherins DCHS1-FAT4 affect functional cerebral architecture. 61
25930014 2016
18
Dachsous1b cadherin regulates actin and microtubule cytoskeleton during early zebrafish embryogenesis. 61
26160902 2015
19
Original Solution for Middle Ear Implant and Anesthetic/Surgical Management in a Child with Severe Craniofacial Dysmorphism. 61
26491591 2015
20
Regulation of neuronal migration by Dchs1-Fat4 planar cell polarity. 61
24998526 2014

Variations for Van Maldergem Syndrome 1

ClinVar genetic disease variations for Van Maldergem Syndrome 1:

6 ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 DCHS1 NM_003737.4(DCHS1):c.2503G>T (p.Gly835Ter)SNV Pathogenic 88997 rs483352917 11:6654240-6654240 11:6633009-6633009
2 DCHS1 NM_003737.4(DCHS1):c.2543del (p.Thr848fs)deletion Pathogenic 88998 rs483352918 11:6654200-6654200 11:6632969-6632969
3 DCHS1 NM_003737.4(DCHS1):c.7109A>T (p.Asn2370Ile)SNV Pathogenic 88999 rs483352919 11:6646466-6646466 11:6625235-6625235
4 FAT4 NM_001291303.3(FAT4):c.6700C>T (p.Arg2234Ter)SNV Likely pathogenic 666967 4:126336818-126336818 4:125415663-125415663
5 DCHS1 NM_003737.4(DCHS1):c.2382G>C (p.Gln794His)SNV Conflicting interpretations of pathogenicity 437929 rs369091875 11:6654716-6654716 11:6633485-6633485
6 DCHS1 NM_003737.4(DCHS1):c.5821A>G (p.Ser1941Gly)SNV Uncertain significance 587461 rs1564861778 11:6648449-6648449 11:6627218-6627218
7 DCHS1 NM_003737.4(DCHS1):c.4114G>A (p.Gly1372Ser)SNV Likely benign 224096 rs869312675 11:6651911-6651911 11:6630680-6630680
8 DCHS1 NM_003737.4(DCHS1):c.3158G>C (p.Trp1053Ser)SNV Likely benign 224097 rs138340204 11:6653585-6653585 11:6632354-6632354

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

73
# 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 13)
# Name GO ID Score Top Affiliating Genes
1 cell adhesion GO:0007155 9.52 FAT4 DCHS1
2 cell-cell adhesion GO:0098609 9.51 FAT4 DCHS1
3 homophilic cell adhesion via plasma membrane adhesion molecules GO:0007156 9.49 FAT4 DCHS1
4 kidney development GO:0001822 9.48 FAT4 DCHS1
5 neurogenesis GO:0022008 9.46 FAT4 DCHS1
6 heart morphogenesis GO:0003007 9.43 FAT4 DCHS1
7 heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules GO:0007157 9.4 FAT4 DCHS1
8 branching involved in ureteric bud morphogenesis GO:0001658 9.37 FAT4 DCHS1
9 digestive tract development GO:0048565 9.32 FAT4 DCHS1
10 hippo signaling GO:0035329 9.26 FAT4 DCHS1
11 nephron development GO:0072006 9.16 FAT4 DCHS1
12 ossification involved in bone maturation GO:0043931 8.96 FAT4 DCHS1
13 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 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
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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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