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

FMD2 MCID: FRN048 MIFTS: 31	Frontometaphyseal Dysplasia 2 (FMD2) Categories: Bone diseases, Ear diseases, Fetal diseases, Genetic diseases, Neuronal diseases, Rare diseases
Genes Variations Tissues Related diseases Publications 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 ⁷³ ²⁹ ⁶

Fmd2 ⁵⁶ 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: Neuronal diseases Bone diseases Ear diseases

See all MalaCards categories (disease lists)

External Ids:

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). 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.

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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
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:

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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:

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
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

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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. ⁵⁶ ⁶	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	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
6	Nitric oxide signaling and its role in oxidative stress response in Schizosaccharomyces pombe. ⁶¹	Astuti RI...Takagi H	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]. ⁶¹	Belenkov IuN...Shchendrygina AA	24888193	2014
8	Transient endothelial dysfunction following flow-mediated dilation assessment. ⁶¹	Nerla R...Crea F	21153030	2011
9	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	1318.01	Molecular basis known ⁵⁶ Pathogenic ⁶ Causative variation ⁷³ Genetic Tests ²⁹ GeneCards inferred via : Disorders Variants (show sections)	25899317 12503106 27426733

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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

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GO Terms for Frontometaphyseal Dysplasia 2

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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

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¹⁴ DiseaseEnhancer

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¹⁶ DrugBank

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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

GO Terms for Frontometaphyseal Dysplasia 2

Sources for Frontometaphyseal Dysplasia 2