FMD2
MCID: FRN048
MIFTS: 28

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 57 74 29 6
Fmd2 57 74

Characteristics:

OMIM:

57
Inheritance:
autosomal dominant


HPO:

32
frontometaphyseal dysplasia 2:
Inheritance autosomal dominant inheritance


Classifications:



External Ids:

MeSH 44 D010009

Summaries for Frontometaphyseal Dysplasia 2

OMIM : 57 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). Affiliated tissues include bone, ovary and uterus, and related phenotypes are low-set ears and high palate

UniProtKB/Swiss-Prot : 74 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 11.7
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

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:

32 (show top 50) (show all 51)
# Description HPO Frequency HPO Source Accession
1 low-set ears 32 occasional (7.5%) HP:0000369
2 high palate 32 occasional (7.5%) HP:0000218
3 sensorineural hearing impairment 32 occasional (7.5%) HP:0000407
4 gastroesophageal reflux 32 occasional (7.5%) HP:0002020
5 feeding difficulties in infancy 32 occasional (7.5%) HP:0008872
6 delayed puberty 32 occasional (7.5%) HP:0000823
7 intellectual disability, mild 32 occasional (7.5%) HP:0001256
8 decreased muscle mass 32 occasional (7.5%) HP:0003199
9 full cheeks 32 occasional (7.5%) HP:0000293
10 cleft palate 32 occasional (7.5%) HP:0000175
11 cryptorchidism 32 occasional (7.5%) HP:0000028
12 webbed neck 32 occasional (7.5%) HP:0000465
13 abnormality of the pinna 32 occasional (7.5%) HP:0000377
14 low anterior hairline 32 occasional (7.5%) HP:0000294
15 pyloric stenosis 32 occasional (7.5%) HP:0002021
16 blue sclerae 32 occasional (7.5%) HP:0000592
17 bifid uvula 32 occasional (7.5%) HP:0000193
18 neurogenic bladder 32 occasional (7.5%) HP:0000011
19 ulcerative colitis 32 occasional (7.5%) HP:0100279
20 hirsutism 32 occasional (7.5%) HP:0001007
21 pierre-robin sequence 32 occasional (7.5%) HP:0000201
22 pectus excavatum 32 very rare (1%) HP:0000767
23 hypertelorism 32 HP:0000316
24 scoliosis 32 HP:0002650
25 prominent supraorbital ridges 32 HP:0000336
26 depressed nasal bridge 32 HP:0005280
27 wide nasal bridge 32 HP:0000431
28 thick eyebrow 32 HP:0000574
29 short philtrum 32 HP:0000322
30 broad nasal tip 32 HP:0000455
31 patent ductus arteriosus 32 HP:0001643
32 bicuspid aortic valve 32 HP:0001647
33 congenital hip dislocation 32 HP:0001374
34 talipes equinovarus 32 HP:0001762
35 downslanted palpebral fissures 32 HP:0000494
36 conductive hearing impairment 32 HP:0000405
37 deep philtrum 32 HP:0002002
38 tracheal stenosis 32 HP:0002777
39 pointed chin 32 HP:0000307
40 pulmonic stenosis 32 HP:0001642
41 hip contracture 32 HP:0003273
42 short metacarpal 32 HP:0010049
43 finger clinodactyly 32 HP:0040019
44 camptodactyly 32 HP:0012385
45 stridor 32 HP:0010307
46 fused cervical vertebrae 32 HP:0002949
47 subglottic stenosis 32 HP:0001607
48 patent foramen ovale 32 HP:0001655
49 dislocated radial head 32 HP:0003083
50 short metatarsal 32 HP:0010743

Symptoms via clinical synopsis from OMIM:

57
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
short philtrum
deep philtrum
small pointed chin
low anterior hairline (in some patients)
more
Cardiovascular Heart:
patent ductus arteriosus
bicuspid aortic valve
patent foramen ovale
pulmonary valve stenosis
aortic root dilation

Skeletal Hands:
camptodactyly
short metacarpals
ulnar deviation of hands
poorly modeled phalanges
fifth-finger clinodactyly
more
Skeletal Limbs:
dislocated radial head
flared metaphyses
flexion contractures of the elbows
limited supination/pronation of the elbows
flexion contractures of the wrists
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:

41
Bone, Ovary, Uterus, Skin, 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. 8 71
27426733 2016
2
Frontometaphyseal dysplasia and keloid formation without FLNA mutations. 8 71
25899317 2015
3
Clinical and genetic heterogeneity in frontometaphyseal dysplasia: severe progressive scoliosis in two families. 8 71
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. 8
10706363 2000
5
Expansion of the clinical spectrum of frontometaphyseal dysplasia 2 caused by the recurrent mutation p.Pro485Leu in MAP3K7. 38
29660408 2018
6
Nitric oxide signaling and its role in oxidative stress response in Schizosaccharomyces pombe. 38
26645666 2016
7
[Effect of 6-month therapy with perindopril A on structural-functional state of arterial vascular bed in patients with chronic heart failure]. 38
24888193 2014
8
Transient endothelial dysfunction following flow-mediated dilation assessment. 38
21153030 2011
9
Inhibition of foot-and-mouth disease virus replication in vitro and in vivo by small interfering RNA. 38
18652701 2008

Variations for Frontometaphyseal Dysplasia 2

ClinVar genetic disease variations for Frontometaphyseal Dysplasia 2:

6
# Gene Variation Type Significance SNP ID GRCh37 Pos GRCh38 Pos
1 MAP3K7 NM_145331.3(MAP3K7): c.1535C> T (p.Pro512Leu) single nucleotide variant Pathogenic rs886039230 6:91228271-91228271 6:90518552-90518552
2 MAP3K7 NM_145331.3(MAP3K7): c.208G> C (p.Glu70Gln) single nucleotide variant Pathogenic rs886039231 6:91281439-91281439 6:90571720-90571720
3 MAP3K7 NM_145331.3(MAP3K7): c.299T> A (p.Val100Glu) single nucleotide variant Pathogenic rs886039232 6:91271385-91271385 6:90561666-90561666
4 MAP3K7 NM_145331.3(MAP3K7): c.502G> C (p.Gly168Arg) single nucleotide variant Pathogenic rs886039233 6:91266324-91266324 6:90556605-90556605

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

74
# 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

GO Terms for Frontometaphyseal Dysplasia 2

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 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
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58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 TGDB
71 Tocris
72 UMLS
73 UMLS via Orphanet
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