Frontometaphyseal Dysplasia 2 (FMD2)

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

Aliases & Classifications for Frontometaphyseal Dysplasia 2

Summaries for Frontometaphyseal Dysplasia 2

OMIM : 58 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. An important gene associated with Frontometaphyseal Dysplasia 2 is MAP3K7 (Mitogen-Activated Protein Kinase Kinase Kinase 7). The drugs Ticagrelor and Clopidogrel have been mentioned in the context of this disorder. Affiliated tissues include bone, skin and testes, and related phenotypes are low-set ears and high palate

UniProtKB/Swiss-Prot : 76 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 11.6

Symptoms & Phenotypes for Frontometaphyseal Dysplasia 2

Human phenotypes related to Frontometaphyseal Dysplasia 2:

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

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

Skeletal Limbs:
dislocated radial head
flared metaphyses
flexion contractures of the elbows
limited supination/pronation of the elbows
flexion contractures of the wrists
Skeletal Feet:
short metatarsals
club feet
undermodeling of metatarsals
short distal phalanges of halluces

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

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
Skeletal Spine:
cervical vertebral fusion
scoliosis, mild to severe

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
Respiratory Larynx:
subglottic stenosis
congenital stridor

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)

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)

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

Drugs for Frontometaphyseal Dysplasia 2 (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 7)
# Name Status Phase Clinical Trials Cas Number PubChem Id
Ticagrelor Approved Phase 4 274693-27-5 9871419
Clopidogrel Approved Phase 4 120202-66-6, 113665-84-2 60606
3 Purinergic P2 Receptor Antagonists Phase 4
4 Purinergic P2Y Receptor Antagonists Phase 4
5 Prasugrel hydrochloride Phase 4 389574-19-0
6 Neurotransmitter Agents Phase 4
7 Platelet Aggregation Inhibitors Phase 4

Interventional clinical trials:

# Name Status NCT ID Phase Drugs
1 Endothelium, Stenting, and Antiplatelet Therapy (EST) - Clopidogrel, Prasugrel, Ticagrelor Study Completed NCT01700322 Phase 4 Ticagrelor;Clopidogrel;Prasugrel

Search 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 30 MAP3K7

Anatomical Context for Frontometaphyseal Dysplasia 2

MalaCards organs/tissues related to Frontometaphyseal Dysplasia 2:

Bone, Skin, Testes, Ovary, Uterus

Publications for Frontometaphyseal Dysplasia 2

Articles related to Frontometaphyseal Dysplasia 2:

# Title Authors Year
Expansion of the clinical spectrum of frontometaphyseal dysplasia 2 caused by the recurrent mutation p.Pro485Leu in MAP3K7. ( 29660408 )
Mutations in MAP3K7 that Alter the Activity of the TAK1 Signaling Complex Cause Frontometaphyseal Dysplasia. ( 27426733 )
Frontometaphyseal dysplasia and keloid formation without FLNA mutations. ( 25899317 )
Clinical and genetic heterogeneity in frontometaphyseal dysplasia: severe progressive scoliosis in two families. ( 12503106 )

Variations for Frontometaphyseal Dysplasia 2

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

ClinVar genetic disease variations for Frontometaphyseal Dysplasia 2:

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

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
20 FMA
29 GO
30 GTR
33 HPO
34 ICD10
35 ICD10 via Orphanet
39 LifeMap
43 MedGen
45 MeSH
46 MESH via Orphanet
47 MGI
50 NCI
51 NCIt
56 Novoseek
59 OMIM via Orphanet
63 PubMed
71 SNOMED-CT via Orphanet
73 Tocris
75 UMLS via Orphanet
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