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 75 29 6
Cerebrofacioarticular Syndrome 57 59 75
Vmlds1 57 75
Van Maldergem Wetzburger Verloes Syndrome 73
Cerebro-Facio-Articular Syndrome 75
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:
Onset and clinical course congenital onset
Inheritance autosomal recessive inheritance


Classifications:



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

UniProtKB/Swiss-Prot : 75 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

Diseases in the Van Maldergem Syndrome family:

Van Maldergem Syndrome 1 Van Maldergem Syndrome 2

Diseases related to Van Maldergem Syndrome 1 via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 van maldergem syndrome 31.4 DCHS1 FAT4
2 hennekam syndrome 30.1 DCHS1 FAT4
3 van maldergem syndrome 2 12.7
4 hypogonadotropic hypogonadism 10.2
5 hypogonadism 10.2
6 renal hypoplasia 9.8 DCHS1 FAT4
7 periventricular nodular heterotopia 9.7 DCHS1 FAT4

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

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

Skeletal Feet:
talipes equinovarus
foot deformities
short fourth metatarsals

Abdomen Gastrointestinal:
anal atresia
anteriorly placed anus
poor feeding

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
mental retardation
simplified gyral pattern
thin corpus callosum
more
Head And Neck Teeth:
dental malocclusion
irregular dentition

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

Genitourinary External Genitalia Male:
hypospadias

Skin Nails Hair Skin:
sacral dimple

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

Human phenotypes related to Van Maldergem Syndrome 1:

32 (show all 47)
# 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 feeding difficulties 32 HP:0011968
16 narrow chest 32 HP:0000774
17 epicanthus 32 HP:0000286
18 growth delay 32 HP:0001510
19 short 4th metacarpal 32 HP:0010044
20 joint laxity 32 HP:0001388
21 talipes equinovarus 32 HP:0001762
22 hypospadias 32 HP:0000047
23 hypoplasia of the maxilla 32 HP:0000327
24 conductive hearing impairment 32 HP:0000405
25 anal atresia 32 HP:0002023
26 downturned corners of mouth 32 HP:0002714
27 renal hypoplasia 32 HP:0000089
28 blepharophimosis 32 HP:0000581
29 sacral dimple 32 HP:0000960
30 midface retrusion 32 HP:0011800
31 wide anterior fontanel 32 HP:0000260
32 tracheomalacia 32 HP:0002779
33 cutaneous finger syndactyly 32 HP:0010554
34 tented upper lip vermilion 32 HP:0010804
35 anteriorly placed anus 32 HP:0001545
36 atresia of the external auditory canal 32 HP:0000413
37 pachygyria 32 HP:0001302
38 generalized hypotonia 32 HP:0001290
39 hypoplasia of the corpus callosum 32 HP:0002079
40 short clavicles 32 HP:0000894
41 heterotopia 32 HP:0002282
42 short palpebral fissure 32 HP:0012745
43 narrow forehead 32 HP:0000341
44 short fourth metatarsal 32 HP:0004689
45 wide cranial sutures 32 HP:0010537
46 irregular dentition 32 HP:0040079
47 cortical gyral simplification 32 HP:0009879

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 9.7 DCHS1
2 Decreased shRNA abundance (Z-score < -2) GR00366-A-109 9.7 DCHS1 FAT4
3 Decreased shRNA abundance (Z-score < -2) GR00366-A-111 9.7 DCHS1
4 Decreased shRNA abundance (Z-score < -2) GR00366-A-153 9.7 DCHS1
5 Decreased shRNA abundance (Z-score < -2) GR00366-A-180 9.7 DCHS1
6 Decreased shRNA abundance (Z-score < -2) GR00366-A-213 9.7 FAT4
7 Decreased shRNA abundance (Z-score < -2) GR00366-A-27 9.7 DCHS1
8 Decreased shRNA abundance (Z-score < -2) GR00366-A-28 9.7 FAT4
9 Decreased shRNA abundance (Z-score < -2) GR00366-A-61 9.7 FAT4
10 Decreased shRNA abundance (Z-score < -2) GR00366-A-68 9.7 FAT4
11 Increased shRNA abundance (Z-score > 2) GR00366-A-114 9.36 DCHS1
12 Increased shRNA abundance (Z-score > 2) GR00366-A-140 9.36 DCHS1
13 Increased shRNA abundance (Z-score > 2) GR00366-A-151 9.36 DCHS1 FAT4
14 Increased shRNA abundance (Z-score > 2) GR00366-A-161 9.36 FAT4
15 Increased shRNA abundance (Z-score > 2) GR00366-A-190 9.36 FAT4
16 Increased shRNA abundance (Z-score > 2) GR00366-A-208 9.36 FAT4
17 Increased shRNA abundance (Z-score > 2) GR00366-A-214 9.36 DCHS1
18 Increased shRNA abundance (Z-score > 2) GR00366-A-30 9.36 FAT4
19 Increased shRNA abundance (Z-score > 2) GR00366-A-42 9.36 FAT4
20 Increased shRNA abundance (Z-score > 2) GR00366-A-83 9.36 DCHS1

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

Publications for Van Maldergem Syndrome 1

Articles related to Van Maldergem Syndrome 1:

# Title Authors Year
1
Van Maldergem syndrome and Hennekam syndrome: Further delineation of allelic phenotypes. ( 29681106 )
2018
2
A newborn diagnosed with van Maldergem syndrome. ( 29505454 )
2018
3
Middle ear abnormalities in Van Maldergem syndrome. ( 27739185 )
2017
4
A patient with van Maldergem syndrome with endocrine abnormalities, hypogonadotropic hypogonadism, and breast aplasia/hypoplasia. ( 29046692 )
2017
5
Hennekam syndrome can be caused by FAT4 mutations and be allelic to Van Maldergem syndrome. ( 24913602 )
2014
6
Van Maldergem syndrome: further characterisation and evidence for neuronal migration abnormalities and autosomal recessive inheritance. ( 22473091 )
2012
7
A further patient with van Maldergem syndrome. ( 22469822 )
2012

Variations for Van Maldergem Syndrome 1

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

75
# Symbol AA change Variation ID SNP ID
1 DCHS1 p.Asn2370Ile VAR_070928 rs483352919

ClinVar genetic disease variations for Van Maldergem Syndrome 1:

6 (show all 12)
# Gene Variation Type Significance SNP ID Assembly Location
1 DCHS1 NM_003737.3(DCHS1): c.2503G> T (p.Gly835Ter) single nucleotide variant Pathogenic rs483352917 GRCh37 Chromosome 11, 6654240: 6654240
2 DCHS1 NM_003737.3(DCHS1): c.2503G> T (p.Gly835Ter) single nucleotide variant Pathogenic rs483352917 GRCh38 Chromosome 11, 6633009: 6633009
3 DCHS1 NM_003737.3(DCHS1): c.2543delC (p.Thr848Asnfs) deletion Pathogenic rs483352918 GRCh37 Chromosome 11, 6654200: 6654200
4 DCHS1 NM_003737.3(DCHS1): c.2543delC (p.Thr848Asnfs) deletion Pathogenic rs483352918 GRCh38 Chromosome 11, 6632969: 6632969
5 DCHS1 NM_003737.3(DCHS1): c.7109A> T (p.Asn2370Ile) single nucleotide variant Pathogenic rs483352919 GRCh37 Chromosome 11, 6646466: 6646466
6 DCHS1 NM_003737.3(DCHS1): c.7109A> T (p.Asn2370Ile) single nucleotide variant Pathogenic rs483352919 GRCh38 Chromosome 11, 6625235: 6625235
7 DCHS1 NM_003737.3(DCHS1): c.4114G> A (p.Gly1372Ser) single nucleotide variant Likely benign rs869312675 GRCh37 Chromosome 11, 6651911: 6651911
8 DCHS1 NM_003737.3(DCHS1): c.4114G> A (p.Gly1372Ser) single nucleotide variant Likely benign rs869312675 GRCh38 Chromosome 11, 6630680: 6630680
9 DCHS1 NM_003737.3(DCHS1): c.3158G> C (p.Trp1053Ser) single nucleotide variant Likely benign rs138340204 GRCh37 Chromosome 11, 6653585: 6653585
10 DCHS1 NM_003737.3(DCHS1): c.3158G> C (p.Trp1053Ser) single nucleotide variant Likely benign rs138340204 GRCh38 Chromosome 11, 6632354: 6632354
11 DCHS1 NM_003737.3(DCHS1): c.2382G> C (p.Gln794His) single nucleotide variant Pathogenic rs369091875 GRCh37 Chromosome 11, 6654716: 6654716
12 DCHS1 NM_003737.3(DCHS1): c.2382G> C (p.Gln794His) single nucleotide variant Pathogenic rs369091875 GRCh38 Chromosome 11, 6633485: 6633485

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 DCHS1 FAT4

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 DCHS1 FAT4

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

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 DCHS1 FAT4

Sources for Van Maldergem Syndrome 1

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
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 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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