VMLDS2
MCID: VNM002
MIFTS: 35

Van Maldergem Syndrome 2 (VMLDS2)

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

Aliases & Classifications for Van Maldergem Syndrome 2

MalaCards integrated aliases for Van Maldergem Syndrome 2:

Name: Van Maldergem Syndrome 2 57 12 72 29 6 15 70
Vmlds2 57 72
Van Maldergem Syndrome, Type 2 39

Characteristics:

OMIM®:

57 (Updated 20-May-2021)
Inheritance:
autosomal recessive

Miscellaneous:
onset at birth
some features may be variable


HPO:

31
van maldergem syndrome 2:
Inheritance autosomal recessive inheritance
Onset and clinical course congenital onset


Classifications:



Summaries for Van Maldergem Syndrome 2

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). For a discussion of genetic heterogeneity of Van Maldergem syndrome, see 601390. (615546) (Updated 20-May-2021)

MalaCards based summary : Van Maldergem Syndrome 2, also known as vmlds2, is related to van maldergem syndrome 1 and renal hypoplasia. An important gene associated with Van Maldergem Syndrome 2 is FAT4 (FAT Atypical Cadherin 4), and among its related pathways/superpathways is Hippo signaling pathway - multiple species. Related phenotypes are intellectual disability and scoliosis

Disease Ontology : 12 A Van Malergem syndrome that has material basis in homozygous or compound heterozygous mutation in the FAT4 gene on chromosome 4q28.

UniProtKB/Swiss-Prot : 72 Van Maldergem syndrome 2: 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 2

Diseases in the Van Maldergem Syndrome family:

Van Maldergem Syndrome 1 Van Maldergem Syndrome 2

Diseases related to Van Maldergem Syndrome 2 via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 van maldergem syndrome 1 9.9 FAT4 DCHS1
2 renal hypoplasia 9.9 FAT4 DCHS1
3 hennekam syndrome 9.8 FAT4 DCHS1
4 periventricular nodular heterotopia 9.7 FAT4 DCHS1
5 van maldergem syndrome 9.1 LINC00251 LINC00222 FAT4 DCHS1 CCDC170

Graphical network of the top 20 diseases related to Van Maldergem Syndrome 2:



Diseases related to Van Maldergem Syndrome 2

Symptoms & Phenotypes for Van Maldergem Syndrome 2

Human phenotypes related to Van Maldergem Syndrome 2:

31 (show all 47)
# Description HPO Frequency HPO Source Accession
1 intellectual disability 31 HP:0001249
2 scoliosis 31 HP:0002650
3 ptosis 31 HP:0000508
4 high palate 31 HP:0000218
5 osteopenia 31 HP:0000938
6 skeletal dysplasia 31 HP:0002652
7 hypertelorism 31 HP:0000316
8 dental malocclusion 31 HP:0000689
9 wide nasal bridge 31 HP:0000431
10 microtia 31 HP:0008551
11 sensorineural hearing impairment 31 HP:0000407
12 cryptorchidism 31 HP:0000028
13 growth delay 31 HP:0001510
14 micrognathia 31 HP:0000347
15 short 4th metacarpal 31 HP:0010044
16 epicanthus 31 HP:0000286
17 joint laxity 31 HP:0001388
18 talipes equinovarus 31 HP:0001762
19 hypoplasia of the maxilla 31 HP:0000327
20 conductive hearing impairment 31 HP:0000405
21 downturned corners of mouth 31 HP:0002714
22 micropenis 31 HP:0000054
23 bifid scrotum 31 HP:0000048
24 malar flattening 31 HP:0000272
25 hypospadias 31 HP:0000047
26 renal hypoplasia 31 HP:0000089
27 blepharophimosis 31 HP:0000581
28 sacral dimple 31 HP:0000960
29 narrow chest 31 HP:0000774
30 midface retrusion 31 HP:0011800
31 wide anterior fontanel 31 HP:0000260
32 tracheomalacia 31 HP:0002779
33 cutaneous finger syndactyly 31 HP:0010554
34 tented upper lip vermilion 31 HP:0010804
35 atresia of the external auditory canal 31 HP:0000413
36 hypoplasia of the corpus callosum 31 HP:0002079
37 feeding difficulties 31 HP:0011968
38 short clavicles 31 HP:0000894
39 generalized hypotonia 31 HP:0001290
40 short palpebral fissure 31 HP:0012745
41 clinodactyly 31 HP:0030084
42 narrow forehead 31 HP:0000341
43 irregular dentition 31 HP:0040079
44 wide cranial sutures 31 HP:0010537
45 short fourth metatarsal 31 HP:0004689
46 periventricular nodular heterotopia 31 HP:0032388
47 subcortical band heterotopia 31 HP:0032409

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Neurologic Central Nervous System:
intellectual disability
periventricular nodular heterotopia
subcortical band heterotopia
mental retardation
thin corpus callosum

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

Head And Neck Teeth:
dental malocclusion
irregular dentition

Genitourinary Internal Genitalia Male:
cryptorchidism

Skeletal Feet:
talipes equinovarus
foot deformities
short fourth metatarsals

Skin Nails Hair Skin:
sacral dimple

Skeletal Hands:
clinodactyly
syndactyly, cutaneous
hand deformities
short fourth metacarpals
flexion of the pip joints
more
Muscle Soft Tissue:
hypotonia

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

Chest External Features:
narrow thorax

Growth Other:
poor growth

Respiratory:
respiratory difficulties due to tracheomalacia

Skeletal Limbs:
subluxation of the radial heads

Skeletal Spine:
scoliosis

Skeletal:
osteopenia
skeletal dysplasia
joint laxity

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

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

Genitourinary External Genitalia Male:
micropenis
bifid scrotum
hypospadias

Chest Ribs Sternum Clavicles And Scapulae:
short clavicles

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

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

Genitourinary Kidneys:
hypoplastic kidneys

Abdomen Gastrointestinal:
poor feeding
anteriorly positioned anus

Head And Neck Head:
large anterior fontanels

Respiratory Airways:
tracheomalacia (tracheostomy may be required)

Clinical features from OMIM®:

615546 (Updated 20-May-2021)

Drugs & Therapeutics for Van Maldergem Syndrome 2

Search Clinical Trials , NIH Clinical Center for Van Maldergem Syndrome 2

Genetic Tests for Van Maldergem Syndrome 2

Genetic tests related to Van Maldergem Syndrome 2:

# Genetic test Affiliating Genes
1 Van Maldergem Syndrome 2 29 FAT4

Anatomical Context for Van Maldergem Syndrome 2

Publications for Van Maldergem Syndrome 2

Articles related to Van Maldergem Syndrome 2:

# Title Authors PMID Year
1
Mutations in genes encoding the cadherin receptor-ligand pair DCHS1 and FAT4 disrupt cerebral cortical development. 57 6
24056717 2013
2
Van Maldergem syndrome: further characterisation and evidence for neuronal migration abnormalities and autosomal recessive inheritance. 6 57
22473091 2012
3
A further patient with van Maldergem syndrome. 6 57
22469822 2012
4
Hennekam syndrome can be caused by FAT4 mutations and be allelic to Van Maldergem syndrome. 6
24913602 2014
5
Autosomal recessive intestinal lymphangiectasia and lymphedema, with facial anomalies and mental retardation. 6
2624276 1989

Variations for Van Maldergem Syndrome 2

ClinVar genetic disease variations for Van Maldergem Syndrome 2:

6 (show all 19)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 FAT4 NM_024582.4(FAT4):c.12476G>T (p.Cys4159Phe) SNV Pathogenic 89004 rs398122953 GRCh37: 4:126400898-126400898
GRCh38: 4:125479743-125479743
2 FAT4 NM_024582.4(FAT4):c.13193G>A (p.Cys4398Tyr) SNV Pathogenic 89005 rs398122954 GRCh37: 4:126411170-126411170
GRCh38: 4:125490015-125490015
3 FAT4 NM_024582.4(FAT4):c.7123G>A (p.Glu2375Lys) SNV Pathogenic 89006 rs398122955 GRCh37: 4:126355504-126355504
GRCh38: 4:125434349-125434349
4 FAT4 NM_024582.4(FAT4):c.9481G>T (p.Glu3161Ter) SNV Pathogenic 89007 rs370088878 GRCh37: 4:126371652-126371652
GRCh38: 4:125450497-125450497
5 FAT4 NM_024582.4(FAT4):c.14512_14513del (p.Ser4838fs) Deletion Pathogenic 89008 rs398122956 GRCh37: 4:126412489-126412490
GRCh38: 4:125491334-125491335
6 FAT4 NM_024582.4(FAT4):c.11455C>T (p.Arg3819Ter) SNV Pathogenic 89009 rs398122957 GRCh37: 4:126373626-126373626
GRCh38: 4:125452471-125452471
7 FAT4 NM_001291303.1(FAT4):c.11800+1G>T SNV Pathogenic 623344 rs963302668 GRCh37: 4:126373966-126373966
GRCh38: 4:125452811-125452811
8 FAT4 NM_001291303.3(FAT4):c.3212T>C (p.Val1071Ala) SNV Uncertain significance 802086 rs200138872 GRCh37: 4:126240778-126240778
GRCh38: 4:125319623-125319623
9 FAT4 NM_001291303.3(FAT4):c.9279A>C (p.Gln3093His) SNV Uncertain significance 813916 rs769424345 GRCh37: 4:126371444-126371444
GRCh38: 4:125450289-125450289
10 FAT4 NM_001291303.3(FAT4):c.9313A>G (p.Ser3105Gly) SNV Uncertain significance 813917 rs764097811 GRCh37: 4:126371478-126371478
GRCh38: 4:125450323-125450323
11 FAT4 NM_024582.4(FAT4):c.8015A>T (p.Asp2672Val) SNV Uncertain significance 420323 rs138655269 GRCh37: 4:126370186-126370186
GRCh38: 4:125449031-125449031
12 FAT4 NM_001291303.3(FAT4):c.3738C>G (p.His1246Gln) SNV Uncertain significance 1064577 GRCh37: 4:126241304-126241304
GRCh38: 4:125320149-125320149
13 FAT4 NM_001291303.3(FAT4):c.13402G>A (p.Val4468Met) SNV Uncertain significance 1028319 GRCh37: 4:126411373-126411373
GRCh38: 4:125490218-125490218
14 FAT4 NM_001291303.3(FAT4):c.13385G>A (p.Arg4462Lys) SNV Uncertain significance 1028318 GRCh37: 4:126411356-126411356
GRCh38: 4:125490201-125490201
15 FAT4 NM_024582.4(FAT4):c.13519G>C (p.Ala4507Pro) SNV Uncertain significance 522673 rs1553931010 GRCh37: 4:126411496-126411496
GRCh38: 4:125490341-125490341
16 FAT4 NM_001291303.1(FAT4):c.10560G>A (p.Met3520Ile) SNV Uncertain significance 522864 rs144506470 GRCh37: 4:126372725-126372725
GRCh38: 4:125451570-125451570
17 FAT4 NM_024582.4(FAT4):c.13393G>A (p.Val4465Met) SNV Uncertain significance 587591 rs1215405311 GRCh37: 4:126411370-126411370
GRCh38: 4:125490215-125490215
18 FAT4 NM_024582.4(FAT4):c.10571G>A (p.Gly3524Asp) SNV Benign 380813 rs1567047 GRCh37: 4:126372742-126372742
GRCh38: 4:125451587-125451587
19 FAT4 NM_024582.4(FAT4):c.11618G>A (p.Ser3873Asn) SNV Benign 380797 rs12650153 GRCh37: 4:126373789-126373789
GRCh38: 4:125452634-125452634

UniProtKB/Swiss-Prot genetic disease variations for Van Maldergem Syndrome 2:

72
# Symbol AA change Variation ID SNP ID
1 FAT4 p.Glu2375Lys VAR_070925 rs398122955
2 FAT4 p.Cys4159Phe VAR_070926 rs398122953
3 FAT4 p.Cys4398Tyr VAR_070927 rs398122954

Expression for Van Maldergem Syndrome 2

Search GEO for disease gene expression data for Van Maldergem Syndrome 2.

Pathways for Van Maldergem Syndrome 2

Pathways related to Van Maldergem Syndrome 2 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 10.09 FAT4 DCHS1

GO Terms for Van Maldergem Syndrome 2

Cellular components related to Van Maldergem Syndrome 2 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 2 according to GeneCards Suite gene sharing:

(show all 12)
# Name GO ID Score Top Affiliating Genes
1 cell-cell adhesion GO:0098609 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 nephron development GO:0072006 9.16 FAT4 DCHS1
11 ossification involved in bone maturation GO:0043931 8.96 FAT4 DCHS1
12 condensed mesenchymal cell proliferation GO:0072137 8.62 FAT4 DCHS1

Sources for Van Maldergem Syndrome 2

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
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
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 20-May-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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