Frontometaphyseal Dysplasia 2 (FMD2)

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

Aliases & Classifications for Frontometaphyseal Dysplasia 2

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). Affiliated tissues include bone, skin and ovary, and related phenotypes are low-set ears and high palate

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 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:

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

Symptoms via clinical synopsis from OMIM:

Head And Neck Eyes:
downslanting palpebral fissures
thick eyebrows
blue sclerae (rare)
full supraorbital region (in some patients)
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)
Cardiovascular Heart:
patent ductus arteriosus
bicuspid aortic valve
patent foramen ovale
pulmonary valve stenosis
aortic root dilation

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


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:

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

Publications for Frontometaphyseal Dysplasia 2

Articles related to Frontometaphyseal Dysplasia 2:

# Title Authors PMID Year
Mutations in MAP3K7 that Alter the Activity of the TAK1 Signaling Complex Cause Frontometaphyseal Dysplasia. 56 6
27426733 2016
Frontometaphyseal dysplasia and keloid formation without FLNA mutations. 56 6
25899317 2015
Clinical and genetic heterogeneity in frontometaphyseal dysplasia: severe progressive scoliosis in two families. 56 6
12503106 2003
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
Expansion of the clinical spectrum of frontometaphyseal dysplasia 2 caused by the recurrent mutation p.Pro485Leu in MAP3K7. 61
29660408 2018
Nitric oxide signaling and its role in oxidative stress response in Schizosaccharomyces pombe. 61
26645666 2016
[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
Transient endothelial dysfunction following flow-mediated dilation assessment. 61
21153030 2011
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:

# 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

9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
31 HPO
32 ICD10
33 ICD10 via Orphanet
37 LifeMap
41 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
54 Novoseek
57 OMIM via Orphanet
61 PubMed
70 Tocris
72 UMLS via Orphanet
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