VMLDS2
MCID: VNM002
MIFTS: 25

Van Maldergem Syndrome 2 (VMLDS2)

Categories: Bone diseases, Ear diseases, Fetal diseases, Genetic diseases, Nephrological 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 58 76 30 6 74
Vmlds2 58 76
Van Maldergem Syndrome, Type 2 41

Characteristics:

OMIM:

58
Inheritance:
autosomal recessive

Miscellaneous:
onset at birth
some features may be variable


HPO:

33
van maldergem syndrome 2:
Onset and clinical course congenital onset
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Van Maldergem Syndrome 2

OMIM : 58 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)

MalaCards based summary : Van Maldergem Syndrome 2, is also known as vmlds2. An important gene associated with Van Maldergem Syndrome 2 is FAT4 (FAT Atypical Cadherin 4). Affiliated tissues include brain and kidney, and related phenotypes are malar flattening and hypertelorism

UniProtKB/Swiss-Prot : 76 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

Symptoms & Phenotypes for Van Maldergem Syndrome 2

Human phenotypes related to Van Maldergem Syndrome 2:

33 (show all 46)
# Description HPO Frequency HPO Source Accession
1 malar flattening 33 HP:0000272
2 hypertelorism 33 HP:0000316
3 clinodactyly 33 HP:0030084
4 high palate 33 HP:0000218
5 ptosis 33 HP:0000508
6 osteopenia 33 HP:0000938
7 intellectual disability 33 HP:0001249
8 scoliosis 33 HP:0002650
9 dental malocclusion 33 HP:0000689
10 skeletal dysplasia 33 HP:0002652
11 wide nasal bridge 33 HP:0000431
12 microtia 33 HP:0008551
13 sensorineural hearing impairment 33 HP:0000407
14 micrognathia 33 HP:0000347
15 feeding difficulties 33 HP:0011968
16 narrow chest 33 HP:0000774
17 epicanthus 33 HP:0000286
18 cryptorchidism 33 HP:0000028
19 growth delay 33 HP:0001510
20 short 4th metacarpal 33 HP:0010044
21 joint laxity 33 HP:0001388
22 talipes equinovarus 33 HP:0001762
23 hypospadias 33 HP:0000047
24 hypoplasia of the maxilla 33 HP:0000327
25 conductive hearing impairment 33 HP:0000405
26 downturned corners of mouth 33 HP:0002714
27 renal hypoplasia 33 HP:0000089
28 blepharophimosis 33 HP:0000581
29 sacral dimple 33 HP:0000960
30 midface retrusion 33 HP:0011800
31 wide anterior fontanel 33 HP:0000260
32 tracheomalacia 33 HP:0002779
33 cutaneous finger syndactyly 33 HP:0010554
34 tented upper lip vermilion 33 HP:0010804
35 bifid scrotum 33 HP:0000048
36 atresia of the external auditory canal 33 HP:0000413
37 micropenis 33 HP:0000054
38 generalized hypotonia 33 HP:0001290
39 hypoplasia of the corpus callosum 33 HP:0002079
40 short clavicles 33 HP:0000894
41 short palpebral fissure 33 HP:0012745
42 irregular dentition 33 HP:0040079
43 narrow forehead 33 HP:0000341
44 short fourth metatarsal 33 HP:0004689
45 wide cranial sutures 33 HP:0010537
46 gray matter heterotopia 33 HP:0002282

Symptoms via clinical synopsis from OMIM:

58
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

Genitourinary Internal Genitalia Male:
cryptorchidism

Genitourinary External Genitalia Male:
hypospadias
bifid scrotum
micropenis

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

Abdomen Gastrointestinal:
poor feeding
anteriorly positioned anus

Growth Other:
poor growth

Respiratory:
respiratory difficulties due to tracheomalacia

Skeletal Limbs:
subluxation of the radial heads

Skeletal Hands:
clinodactyly
syndactyly, cutaneous
hand deformities
short fourth metacarpals
flexion of the pip joints
more
Neurologic Central Nervous System:
intellectual disability
mental retardation
thin corpus callosum
subcortical band heterotopia
periventricular nodular heterotopia

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

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

Chest External Features:
narrow thorax

Head And Neck Head:
large anterior fontanels

Respiratory Airways:
tracheomalacia (tracheostomy may be required)

Clinical features from OMIM:

615546

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 30 FAT4

Anatomical Context for Van Maldergem Syndrome 2

MalaCards organs/tissues related to Van Maldergem Syndrome 2:

42
Brain, Kidney

Publications for Van Maldergem Syndrome 2

Articles related to Van Maldergem Syndrome 2:

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

Variations for Van Maldergem Syndrome 2

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

76
# 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

ClinVar genetic disease variations for Van Maldergem Syndrome 2:

6 (show all 22)
# Gene Variation Type Significance SNP ID Assembly Location
1 FAT4 NM_024582.4(FAT4): c.12476G> T (p.Cys4159Phe) single nucleotide variant Pathogenic rs398122953 GRCh37 Chromosome 4, 126400898: 126400898
2 FAT4 NM_024582.4(FAT4): c.12476G> T (p.Cys4159Phe) single nucleotide variant Pathogenic rs398122953 GRCh38 Chromosome 4, 125479743: 125479743
3 FAT4 NM_024582.4(FAT4): c.13193G> A (p.Cys4398Tyr) single nucleotide variant Pathogenic rs398122954 GRCh37 Chromosome 4, 126411170: 126411170
4 FAT4 NM_024582.4(FAT4): c.13193G> A (p.Cys4398Tyr) single nucleotide variant Pathogenic rs398122954 GRCh38 Chromosome 4, 125490015: 125490015
5 FAT4 NM_024582.4(FAT4): c.7123G> A (p.Glu2375Lys) single nucleotide variant Pathogenic rs398122955 GRCh37 Chromosome 4, 126355504: 126355504
6 FAT4 NM_024582.4(FAT4): c.7123G> A (p.Glu2375Lys) single nucleotide variant Pathogenic rs398122955 GRCh38 Chromosome 4, 125434349: 125434349
7 FAT4 NM_024582.4(FAT4): c.9481G> T (p.Glu3161Ter) single nucleotide variant Pathogenic rs370088878 GRCh37 Chromosome 4, 126371652: 126371652
8 FAT4 NM_024582.4(FAT4): c.9481G> T (p.Glu3161Ter) single nucleotide variant Pathogenic rs370088878 GRCh38 Chromosome 4, 125450497: 125450497
9 FAT4 NM_024582.4(FAT4): c.14512_14513del (p.Ser4838Leufs) deletion Pathogenic rs398122956 GRCh37 Chromosome 4, 126412489: 126412490
10 FAT4 NM_024582.4(FAT4): c.14512_14513del (p.Ser4838Leufs) deletion Pathogenic rs398122956 GRCh38 Chromosome 4, 125491334: 125491335
11 FAT4 NM_024582.4(FAT4): c.11455C> T (p.Arg3819Ter) single nucleotide variant Pathogenic rs398122957 GRCh37 Chromosome 4, 126373626: 126373626
12 FAT4 NM_024582.4(FAT4): c.11455C> T (p.Arg3819Ter) single nucleotide variant Pathogenic rs398122957 GRCh38 Chromosome 4, 125452471: 125452471
13 FAT4 NM_024582.4(FAT4): c.8015A> T (p.Asp2672Val) single nucleotide variant Uncertain significance rs138655269 GRCh38 Chromosome 4, 125449031: 125449031
14 FAT4 NM_024582.4(FAT4): c.8015A> T (p.Asp2672Val) single nucleotide variant Uncertain significance rs138655269 GRCh37 Chromosome 4, 126370186: 126370186
15 FAT4 NM_024582.4(FAT4): c.13519G> C (p.Ala4507Pro) single nucleotide variant Uncertain significance rs1553931010 GRCh37 Chromosome 4, 126411496: 126411496
16 FAT4 NM_024582.4(FAT4): c.13519G> C (p.Ala4507Pro) single nucleotide variant Uncertain significance rs1553931010 GRCh38 Chromosome 4, 125490341: 125490341
17 FAT4 NM_001291303.1(FAT4): c.10560G> A (p.Met3520Ile) single nucleotide variant Uncertain significance rs144506470 GRCh37 Chromosome 4, 126372725: 126372725
18 FAT4 NM_001291303.1(FAT4): c.10560G> A (p.Met3520Ile) single nucleotide variant Uncertain significance rs144506470 GRCh38 Chromosome 4, 125451570: 125451570
19 FAT4 NM_024582.4(FAT4): c.13393G> A (p.Val4465Met) single nucleotide variant Uncertain significance GRCh38 Chromosome 4, 125490215: 125490215
20 FAT4 NM_024582.4(FAT4): c.13393G> A (p.Val4465Met) single nucleotide variant Uncertain significance GRCh37 Chromosome 4, 126411370: 126411370
21 FAT4 NM_001291303.1(FAT4): c.11800+1G> T single nucleotide variant Pathogenic GRCh38 Chromosome 4, 125452811: 125452811
22 FAT4 NM_001291303.1(FAT4): c.11800+1G> T single nucleotide variant Pathogenic GRCh37 Chromosome 4, 126373966: 126373966

Expression for Van Maldergem Syndrome 2

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

Pathways for Van Maldergem Syndrome 2

GO Terms for Van Maldergem Syndrome 2

Sources for Van Maldergem Syndrome 2

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75 UMLS via Orphanet
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