FMD2
MCID: FRN048
MIFTS: 35

Frontometaphyseal Dysplasia 2 (FMD2)

Categories: Bone diseases, Ear diseases, Fetal diseases, Genetic diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Frontometaphyseal Dysplasia 2

MalaCards integrated aliases for Frontometaphyseal Dysplasia 2:

Name: Frontometaphyseal Dysplasia 2 56 12 73 29 6 15
Fmd2 56 12 73

Characteristics:

OMIM:

56
Inheritance:
autosomal dominant


HPO:

31
frontometaphyseal dysplasia 2:
Inheritance autosomal dominant inheritance


Classifications:



Summaries for Frontometaphyseal Dysplasia 2

OMIM : 56 Frontometaphyseal dysplasia (FMD) is a progressive sclerosing skeletal dysplasia characterized by supraorbital hyperostosis, undermodeling of the small bones, and small and large joint contractures, as well as extraskeletal developmental abnormalities, primarily of the cardiorespiratory system and genitourinary tract. Patients with FMD2 appear to have a propensity for keloid formation (summary by Wade et al., 2016). For a discussion of genetic heterogeneity of frontometaphyseal dysplasia, see FMD1 (305620). (617137)

MalaCards based summary : Frontometaphyseal Dysplasia 2, also known as fmd2, is related to frontometaphyseal dysplasia and neural tube defects. An important gene associated with Frontometaphyseal Dysplasia 2 is MAP3K7 (Mitogen-Activated Protein Kinase Kinase Kinase 7), and among its related pathways/superpathways is Wnt Signaling Pathway and Pluripotency. Affiliated tissues include bone, skin and ovary, and related phenotypes are sensorineural hearing impairment and gastroesophageal reflux

Disease Ontology : 12 A frontometaphyseal dysplasia characterized by generalized skeletal dysplasia, deafness, urogenital defects and an increased tendency to form keloid scars that has material basis in heterozygous mutation in MAP3K7 on chromosome 6q15.

UniProtKB/Swiss-Prot : 73 Frontometaphyseal dysplasia 2: A form of frontometaphyseal dysplasia, a progressive sclerosing skeletal dysplasia affecting the long bones and skull. Characteristic features include supraorbital hyperostosis, cranial hyperostosis, undermodeling of the small bones, flared metaphyses, and digital anomalies. Extra-skeletal manifestations include hearing loss, cardiac malformations, and stenosis, particularly of the upper airway and urinary tract. FMD2 inheritance is autosomal dominant.

Related Diseases for Frontometaphyseal Dysplasia 2

Diseases in the Frontometaphyseal Dysplasia family:

Frontometaphyseal Dysplasia 1 Frontometaphyseal Dysplasia 2

Diseases related to Frontometaphyseal Dysplasia 2 via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 frontometaphyseal dysplasia 32.3 MAP3K7 ADGRV1
2 neural tube defects 10.1
3 alacrima, achalasia, and mental retardation syndrome 10.1
4 spina bifida occulta 10.1
5 hyperostosis 10.1
6 keloid disorder 10.1
7 frontometaphyseal dysplasia 1 9.2 H1-5 FBXW2 ADGRV1

Graphical network of the top 20 diseases related to Frontometaphyseal Dysplasia 2:



Diseases related to Frontometaphyseal Dysplasia 2

Symptoms & Phenotypes for Frontometaphyseal Dysplasia 2

Human phenotypes related to Frontometaphyseal Dysplasia 2:

31 (show all 50)
# Description HPO Frequency HPO Source Accession
1 sensorineural hearing impairment 31 occasional (7.5%) HP:0000407
2 gastroesophageal reflux 31 occasional (7.5%) HP:0002020
3 feeding difficulties in infancy 31 occasional (7.5%) HP:0008872
4 delayed puberty 31 occasional (7.5%) HP:0000823
5 intellectual disability, mild 31 occasional (7.5%) HP:0001256
6 decreased muscle mass 31 occasional (7.5%) HP:0003199
7 full cheeks 31 occasional (7.5%) HP:0000293
8 cryptorchidism 31 occasional (7.5%) HP:0000028
9 high palate 31 occasional (7.5%) HP:0000218
10 low-set ears 31 occasional (7.5%) HP:0000369
11 webbed neck 31 occasional (7.5%) HP:0000465
12 low anterior hairline 31 occasional (7.5%) HP:0000294
13 pyloric stenosis 31 occasional (7.5%) HP:0002021
14 blue sclerae 31 occasional (7.5%) HP:0000592
15 bifid uvula 31 occasional (7.5%) HP:0000193
16 hirsutism 31 occasional (7.5%) HP:0001007
17 pierre-robin sequence 31 occasional (7.5%) HP:0000201
18 abnormality of the pinna 31 occasional (7.5%) HP:0000377
19 neurogenic bladder 31 occasional (7.5%) HP:0000011
20 ulcerative colitis 31 occasional (7.5%) HP:0100279
21 pectus excavatum 31 very rare (1%) HP:0000767
22 depressed nasal bridge 31 HP:0005280
23 hypertelorism 31 HP:0000316
24 prominent supraorbital ridges 31 HP:0000336
25 scoliosis 31 HP:0002650
26 wide nasal bridge 31 HP:0000431
27 thick eyebrow 31 HP:0000574
28 bicuspid aortic valve 31 HP:0001647
29 congenital hip dislocation 31 HP:0001374
30 talipes equinovarus 31 HP:0001762
31 downslanted palpebral fissures 31 HP:0000494
32 conductive hearing impairment 31 HP:0000405
33 patent ductus arteriosus 31 HP:0001643
34 deep philtrum 31 HP:0002002
35 short philtrum 31 HP:0000322
36 pointed chin 31 HP:0000307
37 pulmonic stenosis 31 HP:0001642
38 hip contracture 31 HP:0003273
39 short metacarpal 31 HP:0010049
40 stridor 31 HP:0010307
41 fused cervical vertebrae 31 HP:0002949
42 tracheal stenosis 31 HP:0002777
43 dislocated radial head 31 HP:0003083
44 broad nasal tip 31 HP:0000455
45 subglottic stenosis 31 HP:0001607
46 camptodactyly 31 HP:0012385
47 short metatarsal 31 HP:0010743
48 finger clinodactyly 31 HP:0040019
49 patent foramen ovale 31 HP:0001655
50 ulnar deviation of the hand 31 HP:0009487

Symptoms via clinical synopsis from OMIM:

56
Head And Neck Eyes:
hypertelorism
downslanting palpebral fissures
thick eyebrows
blue sclerae (rare)
full supraorbital region (in some patients)
more
Head And Neck Nose:
wide nasal bridge
broad nasal tip
low nasal bridge
grooving of nasal tip (in some patients)

Respiratory Airways:
tracheal stenosis

Respiratory Larynx:
subglottic stenosis
congenital stridor

Skeletal Feet:
short metatarsals
club feet
undermodeling of metatarsals
short distal phalanges of halluces

Neurologic Central Nervous System:
intellectual disability, mild (in some patients)

Skeletal Spine:
scoliosis, mild to severe
cervical vertebral fusion

Skeletal Pelvis:
hip contractures
congenital dislocation of the hip

Skin Nails Hair Hair:
hirsutism (in some patients)
low anterior hairline (in some patients)

Muscle Soft Tissue:
underdeveloped muscles (in some patients)

Head And Neck Teeth:
noneruption of multiple permanent teeth irregularly implanted teeth

Abdomen External Features:
supraumbilical hernia (rare)

Genitourinary Internal Genitalia Female:
absent ovaries by ultrasound (rare)
absent uterus by ultrasound (rare)

Genitourinary Ureters:
bilateral hydroureters (rare)

Skin Nails Hair Skin:
keloid formation (in some patients)
soft translucent skin (rare)
deep sacral dimples (rare)

Head And Neck Face:
prominent supraorbital ridges
deep philtrum
short philtrum
small pointed chin
low anterior hairline (in some patients)
more
Cardiovascular Heart:
bicuspid aortic valve
patent ductus arteriosus
patent foramen ovale
pulmonary valve stenosis
aortic root dilation

Skeletal Limbs:
dislocated radial head
flared metaphyses
flexion contractures of the elbows
limited supination/pronation of the elbows
flexion contractures of the wrists
more
Skeletal Hands:
camptodactyly
short metacarpals
ulnar deviation of hands
poorly modeled phalanges
fifth-finger clinodactyly
more
Head And Neck Ears:
hearing loss, conductive
sensorineural hearing loss (in some patients)
low-set ears (in some patients)
malformed ears (in some patients)

Head And Neck Mouth:
cleft palate (in some patients)
bifid uvula (in some patients)
high palate (in some patients)
thin upper vermilion (in some patients)
pierre-robin sequence (rare)

Abdomen Gastrointestinal:
gastroesophageal reflux (rare)
feeding difficulties in infancy (rare)
pyloric stenosis (rare)
ulcerative colitis (rare)

Chest Ribs Sternum Clavicles And Scapulae:
pectus excavatum (rare)
undermodeled ribs (in some patients)
deformed ribs (in some patients)

Skeletal Skull:
skull base sclerosis
dense skull
sclerosis of frontal bone
underdeveloped sinuses
narrowing of acoustic external canal
more
Growth Height:
stature below 10th centile

Head And Neck Neck:
short webbed neck (rare)
pterygium colli (rare)

Genitourinary Internal Genitalia Male:
undescended testes (rare)

Genitourinary Kidneys:
bilateral hydronephrosis (rare)

Genitourinary Bladder:
neurogenic bladder (rare)

Endocrine Features:
delayed puberty (rare)

Clinical features from OMIM:

617137

Drugs & Therapeutics for Frontometaphyseal Dysplasia 2

Search Clinical Trials , NIH Clinical Center for Frontometaphyseal Dysplasia 2

Genetic Tests for Frontometaphyseal Dysplasia 2

Genetic tests related to Frontometaphyseal Dysplasia 2:

# Genetic test Affiliating Genes
1 Frontometaphyseal Dysplasia 2 29 MAP3K7

Anatomical Context for Frontometaphyseal Dysplasia 2

MalaCards organs/tissues related to Frontometaphyseal Dysplasia 2:

40
Bone, Skin, Ovary, Uterus, Testes, Heart, Endothelial

Publications for Frontometaphyseal Dysplasia 2

Articles related to Frontometaphyseal Dysplasia 2:

# Title Authors PMID Year
1
Mutations in MAP3K7 that Alter the Activity of the TAK1 Signaling Complex Cause Frontometaphyseal Dysplasia. 56 6
27426733 2016
2
Frontometaphyseal dysplasia and keloid formation without FLNA mutations. 6 56
25899317 2015
3
Clinical and genetic heterogeneity in frontometaphyseal dysplasia: severe progressive scoliosis in two families. 56 6
12503106 2003
4
Fronto-otopalatodigital osteodysplasia: clinical evidence for a single entity encompassing Melnick-Needles syndrome, otopalatodigital syndrome types 1 and 2, and frontometaphyseal dysplasia. 56
10706363 2000
5
A novel variant in MAP3K7 associated with an expanded cardiospondylocarpofacial syndrome phenotype. 61
32299812 2020
6
Expansion of the clinical spectrum of frontometaphyseal dysplasia 2 caused by the recurrent mutation p.Pro485Leu in MAP3K7. 61
29660408 2018
7
Nitric oxide signaling and its role in oxidative stress response in Schizosaccharomyces pombe. 61
26645666 2016
8
[Effect of 6-month therapy with perindopril A on structural-functional state of arterial vascular bed in patients with chronic heart failure]. 61
24888193 2014
9
Transient endothelial dysfunction following flow-mediated dilation assessment. 61
21153030 2011
10
Inhibition of foot-and-mouth disease virus replication in vitro and in vivo by small interfering RNA. 61
18652701 2008

Variations for Frontometaphyseal Dysplasia 2

ClinVar genetic disease variations for Frontometaphyseal Dysplasia 2:

6 ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 MAP3K7 NM_145331.3(MAP3K7):c.1535C>T (p.Pro512Leu)SNV Pathogenic 264698 rs886039230 6:91228271-91228271 6:90518552-90518552
2 MAP3K7 NM_145331.3(MAP3K7):c.208G>C (p.Glu70Gln)SNV Pathogenic 264699 rs886039231 6:91281439-91281439 6:90571720-90571720
3 MAP3K7 NM_145331.3(MAP3K7):c.299T>A (p.Val100Glu)SNV Pathogenic 264700 rs886039232 6:91271385-91271385 6:90561666-90561666
4 MAP3K7 NM_145331.3(MAP3K7):c.502G>C (p.Gly168Arg)SNV Pathogenic 264701 rs886039233 6:91266324-91266324 6:90556605-90556605
5 MAP3K7 NM_145331.3(MAP3K7):c.608-1G>ASNV Likely pathogenic 801006 6:91263306-91263306 6:90553587-90553587

UniProtKB/Swiss-Prot genetic disease variations for Frontometaphyseal Dysplasia 2:

73
# Symbol AA change Variation ID SNP ID
1 MAP3K7 p.Glu70Gln VAR_077342 rs886039231
2 MAP3K7 p.Val100Glu VAR_077343 rs886039232
3 MAP3K7 p.Gly168Arg VAR_077345 rs886039233
4 MAP3K7 p.Pro512Leu VAR_077347 rs886039230

Expression for Frontometaphyseal Dysplasia 2

Search GEO for disease gene expression data for Frontometaphyseal Dysplasia 2.

Pathways for Frontometaphyseal Dysplasia 2

Pathways related to Frontometaphyseal Dysplasia 2 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
10.87 MAP3K7 FBXW2

GO Terms for Frontometaphyseal Dysplasia 2

Biological processes related to Frontometaphyseal Dysplasia 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 protein stabilization GO:0050821 8.62 PER3 H1-5

Sources for Frontometaphyseal Dysplasia 2

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
45 MGI
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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