Frontometaphyseal Dysplasia 2 disease: Malacards - Research Articles, Drugs, Genes, Clinical Trials

FMD2 MCID: FRN048 MIFTS: 35	Frontometaphyseal Dysplasia 2 (FMD2) Categories: Bone diseases, Ear diseases, Fetal diseases, Genetic diseases, Neuronal diseases, Rare diseases
Genes Variations Tissues Related diseases Publications Pathways Symptoms & Phenotypes Expand all tables

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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:

MalaCards categories:
Global: Genetic diseases Rare diseases Fetal diseases
Anatomical: Bone diseases Neuronal diseases Ear diseases

See all MalaCards categories (disease lists)

External Ids:

Disease Ontology ¹² DOID:0111787

OMIM ⁵⁶ 617137

OMIM Phenotypic Series ⁵⁶ PS305620

MeSH ⁴³ D010009

MedGen ⁴¹ C4310697 CN238524

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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.

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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:

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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

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Drugs & Therapeutics for Frontometaphyseal Dysplasia 2

Search Clinical Trials , NIH Clinical Center for Frontometaphyseal Dysplasia 2

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Genetic Tests for Frontometaphyseal Dysplasia 2

Genetic tests related to Frontometaphyseal Dysplasia 2:

#	Genetic test	Affiliating Genes
1	Frontometaphyseal Dysplasia 2 ²⁹	MAP3K7

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Anatomical Context for Frontometaphyseal Dysplasia 2

MalaCards organs/tissues related to Frontometaphyseal Dysplasia 2:

⁴⁰

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

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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	Wade EM...Robertson SP	27426733	2016
2	Frontometaphyseal dysplasia and keloid formation without FLNA mutations. ⁶ ⁵⁶	Basart H...Hennekam RC	25899317	2015
3	Clinical and genetic heterogeneity in frontometaphyseal dysplasia: severe progressive scoliosis in two families. ⁵⁶ ⁶	Morava E...Kosztolanyi G	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	Verloes A...Roeder E	10706363	2000
5	A novel variant in MAP3K7 associated with an expanded cardiospondylocarpofacial syndrome phenotype. ⁶¹	AbuBakr F...Lakhani SA	32299812	2020
6	Expansion of the clinical spectrum of frontometaphyseal dysplasia 2 caused by the recurrent mutation p.Pro485Leu in MAP3K7. ⁶¹	Costantini A...Makitie O	29660408	2018
7	Nitric oxide signaling and its role in oxidative stress response in Schizosaccharomyces pombe. ⁶¹	Astuti RI...Takagi H	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	Belenkov IuN...Shchendrygina AA	24888193	2014
9	Transient endothelial dysfunction following flow-mediated dilation assessment. ⁶¹	Nerla R...Crea F	21153030	2011
10	Inhibition of foot-and-mouth disease virus replication in vitro and in vivo by small interfering RNA. ⁶¹	Pengyan W...Chuangfu C	18652701	2008

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Genes for Frontometaphyseal Dysplasia 2

Genes related to Frontometaphyseal Dysplasia 2 (1 elite genes):

- Elite gene

- Cancer Census gene in COSMIC

#	Symbol	Description	Category	Score	Evidence	PubmedIds
1	MAP3K7	Mitogen-Activated Protein Kinase Kinase Kinase 7	Protein Coding	1323.72	Molecular basis known ⁵⁶ Pathogenic ⁶ Causative variation ⁷³ Genetic Tests ²⁹ DISEASES inferred ¹⁵ GeneCards inferred via : Disorders Variants (show sections)	25899317 12503106 27426733
2	ADGRV1	Adhesion G Protein-Coupled Receptor V1	Protein Coding	6.85	DISEASES inferred ¹⁵
3	FBXW2	F-Box And WD Repeat Domain Containing 2	Protein Coding	5.83	DISEASES inferred ¹⁵
4	H1-5	H1.5 Linker Histone, Cluster Member	Protein Coding	5.64	DISEASES inferred ¹⁵
5	KLHL24	Kelch Like Family Member 24	Protein Coding	5.35	DISEASES inferred ¹⁵
6	CCDC65	Coiled-Coil Domain Containing 65	Protein Coding	5.31	DISEASES inferred ¹⁵
7	PER3	Period Circadian Regulator 3	Protein Coding	5.29	DISEASES inferred ¹⁵

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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>A	SNV	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

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Expression for Frontometaphyseal Dysplasia 2

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

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Pathways for Frontometaphyseal Dysplasia 2

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

#	Super pathways	Score	Top Affiliating Genes
1	Wnt Signaling Pathway and Pluripotency ¹ Show member pathways Wnt Signaling Pathway ¹	10.87	MAP3K7 FBXW2

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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

Sources for Frontometaphyseal Dysplasia 2

¹ BioSystems

² BitterDB

³ CDC

⁴ Cell Signaling Technology

⁵ ClinicalTrials

⁶ ClinVar

⁷ CNVD

⁸ Cochrane Library

⁹ Cosmic

¹⁰ dbSNP

¹¹ DGIdb

¹² Disease Ontology

¹³ diseasecard

¹⁴ DiseaseEnhancer

¹⁵ DISEASES

¹⁶ DrugBank

¹⁷ EFO

¹⁸ ExPASy

¹⁹ FMA

²⁰ GeneAnalytics

²¹ GeneCards

²² GeneGo (Thomson Reuters)

²³ GeneHancer via GeneCards

²⁴ GeneReviews

²⁵ Genetics Home Reference

²⁶ GenomeRNAi

²⁷ GEO DataSets

²⁸ GO

²⁹ GTR

³⁰ HMDB

³¹ HPO

³² ICD10

³³ ICD10 via Orphanet

³⁴ ICD9CM

³⁵ IUPHAR

³⁶ KEGG

³⁷ LifeMap

³⁸ LncRNADisease

³⁹ LOVD

⁴⁰ MalaCards

⁴¹ MedGen

⁴² MedlinePlus

⁴³ MeSH

⁴⁴ MESH via Orphanet

⁴⁵ MGI

⁴⁶ miR2Disease

⁴⁷ NCBI Bookshelf

⁴⁸ NCI

⁴⁹ NCIt

⁵⁰ NDF-RT

⁵¹ NIH Clinical Center

⁵² NIH Rare Diseases

⁵³ NINDS

⁵⁴ Novoseek

⁵⁵ Novus Biologicals

⁵⁶ OMIM

⁵⁷ OMIM via Orphanet

⁵⁸ Orphanet

⁵⁹ PathCards

⁶⁰ PharmGKB

⁶¹ PubMed

⁶² PubMed Health

⁶³ QIAGEN

⁶⁴ R&D Systems

⁶⁵ Reactome

⁶⁶ Sino Biological

⁶⁷ SNOMED-CT

⁶⁸ SNOMED-CT via HPO

⁶⁹ TGDB

⁷⁰ Tocris

⁷¹ UMLS

⁷² UMLS via Orphanet

⁷³ UniProtKB/Swiss-Prot

⁷⁴ Wikipedia

Frontometaphyseal Dysplasia 2 (FMD2)

Aliases & Classifications for Frontometaphyseal Dysplasia 2

MalaCards integrated aliases for Frontometaphyseal Dysplasia 2:

Characteristics:

OMIM:

HPO:

Classifications:

External Ids:

Summaries for Frontometaphyseal Dysplasia 2

Related Diseases for Frontometaphyseal Dysplasia 2

Diseases in the Frontometaphyseal Dysplasia family:

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

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

Symptoms & Phenotypes for Frontometaphyseal Dysplasia 2

Human phenotypes related to Frontometaphyseal Dysplasia 2:

Symptoms via clinical synopsis from OMIM:

Clinical features from OMIM:

Drugs & Therapeutics for Frontometaphyseal Dysplasia 2

Genetic Tests for Frontometaphyseal Dysplasia 2

Genetic tests related to Frontometaphyseal Dysplasia 2:

Anatomical Context for Frontometaphyseal Dysplasia 2

MalaCards organs/tissues related to Frontometaphyseal Dysplasia 2:

Publications for Frontometaphyseal Dysplasia 2

Articles related to Frontometaphyseal Dysplasia 2:

Genes for Frontometaphyseal Dysplasia 2

Genes related to Frontometaphyseal Dysplasia 2 (1 elite genes):

Variations for Frontometaphyseal Dysplasia 2

ClinVar genetic disease variations for Frontometaphyseal Dysplasia 2:

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

Expression for Frontometaphyseal Dysplasia 2

Pathways for Frontometaphyseal Dysplasia 2

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

GO Terms for Frontometaphyseal Dysplasia 2

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

Sources for Frontometaphyseal Dysplasia 2