MCID: FRN048
MIFTS: 29

Frontometaphyseal Dysplasia 2

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

Aliases & Classifications for Frontometaphyseal Dysplasia 2

MalaCards integrated aliases for Frontometaphyseal Dysplasia 2:

Name: Frontometaphyseal Dysplasia 2 57 75 29 6
Fmd2 57 75

Characteristics:

OMIM:

57
Inheritance:
autosomal dominant


HPO:

32
frontometaphyseal dysplasia 2:
Inheritance autosomal dominant inheritance


Classifications:



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. An important gene associated with Frontometaphyseal Dysplasia 2 is MAP3K7 (Mitogen-Activated Protein Kinase Kinase Kinase 7). The drugs Clopidogrel and Ticagrelor have been mentioned in the context of this disorder. Affiliated tissues include bone, testes and uterus, and related phenotypes are neurogenic bladder and cryptorchidism

UniProtKB/Swiss-Prot : 75 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 11.4

Symptoms & Phenotypes for Frontometaphyseal Dysplasia 2

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

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 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
more
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)
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
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)

GenitourinaryInternal GenitaliaMale:
undescended testes (rare)

Genitourinary Kidneys:
bilateral hydronephrosis (rare)

Genitourinary Bladder:
neurogenic bladder (rare)

Endocrine Features:
delayed puberty (rare)


Clinical features from OMIM:

617137

Human phenotypes related to Frontometaphyseal Dysplasia 2:

32 (show all 48)
# Description HPO Frequency HPO Source Accession
1 neurogenic bladder 32 occasional (7.5%) HP:0000011
2 cryptorchidism 32 occasional (7.5%) HP:0000028
3 cleft palate 32 occasional (7.5%) HP:0000175
4 bifid uvula 32 occasional (7.5%) HP:0000193
5 pierre-robin sequence 32 occasional (7.5%) HP:0000201
6 high palate 32 occasional (7.5%) HP:0000218
7 full cheeks 32 occasional (7.5%) HP:0000293
8 low anterior hairline 32 occasional (7.5%) HP:0000294
9 pointed chin 32 HP:0000307
10 hypertelorism 32 HP:0000316
11 short philtrum 32 HP:0000322
12 prominent supraorbital ridges 32 HP:0000336
13 low-set ears 32 occasional (7.5%) HP:0000369
14 abnormality of the pinna 32 occasional (7.5%) HP:0000377
15 conductive hearing impairment 32 HP:0000405
16 sensorineural hearing impairment 32 occasional (7.5%) HP:0000407
17 wide nasal bridge 32 HP:0000431
18 broad nasal tip 32 HP:0000455
19 webbed neck 32 occasional (7.5%) HP:0000465
20 downslanted palpebral fissures 32 HP:0000494
21 thick eyebrow 32 HP:0000574
22 blue sclerae 32 occasional (7.5%) HP:0000592
23 delayed puberty 32 occasional (7.5%) HP:0000823
24 hirsutism 32 occasional (7.5%) HP:0001007
25 intellectual disability, mild 32 occasional (7.5%) HP:0001256
26 congenital hip dislocation 32 HP:0001374
27 subglottic stenosis 32 HP:0001607
28 pulmonic stenosis 32 HP:0001642
29 patent ductus arteriosus 32 HP:0001643
30 bicuspid aortic valve 32 HP:0001647
31 patent foramen ovale 32 HP:0001655
32 talipes equinovarus 32 HP:0001762
33 deep philtrum 32 HP:0002002
34 gastroesophageal reflux 32 occasional (7.5%) HP:0002020
35 pyloric stenosis 32 occasional (7.5%) HP:0002021
36 scoliosis 32 HP:0002650
37 tracheal stenosis 32 HP:0002777
38 fused cervical vertebrae 32 HP:0002949
39 dislocated radial head 32 HP:0003083
40 decreased muscle mass 32 occasional (7.5%) HP:0003199
41 hip contracture 32 HP:0003273
42 depressed nasal bridge 32 HP:0005280
43 feeding difficulties in infancy 32 occasional (7.5%) HP:0008872
44 ulnar deviation of the hand 32 HP:0009487
45 short metacarpal 32 HP:0010049
46 short metatarsal 32 HP:0010743
47 camptodactyly 32 HP:0012385
48 ulcerative colitis 32 occasional (7.5%) HP:0100279

Drugs & Therapeutics for Frontometaphyseal Dysplasia 2

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

(show all 10)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Clopidogrel Approved Phase 4 120202-66-6, 113665-84-2 60606
2
Ticagrelor Approved Phase 4 274693-27-5 9871419
3
Ticlopidine Approved Phase 4 55142-85-3 5472
4 Cytochrome P-450 Enzyme Inhibitors Phase 4
5 Fibrinolytic Agents Phase 4
6 Neurotransmitter Agents Phase 4
7 Platelet Aggregation Inhibitors Phase 4
8 Prasugrel hydrochloride Phase 4 389574-19-0
9 Purinergic P2 Receptor Antagonists Phase 4
10 Purinergic P2Y Receptor Antagonists 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 29 MAP3K7

Anatomical Context for Frontometaphyseal Dysplasia 2

MalaCards organs/tissues related to Frontometaphyseal Dysplasia 2:

41
Bone, Testes, Uterus, Ovary, Skin

Publications for Frontometaphyseal Dysplasia 2

Articles related to Frontometaphyseal Dysplasia 2:

# Title Authors Year
1
Expansion of the clinical spectrum of frontometaphyseal dysplasia 2 caused by the recurrent mutation p.Pro485Leu in MAP3K7. ( 29660408 )
2018

Variations for Frontometaphyseal Dysplasia 2

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

75
# 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:

6
# 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

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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