MCID: FRN012
MIFTS: 43

Frontometaphyseal Dysplasia

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

Aliases & Classifications for Frontometaphyseal Dysplasia

MalaCards integrated aliases for Frontometaphyseal Dysplasia:

Name: Frontometaphyseal Dysplasia 49 24 55 36 28 13 51 69
Fmd 24

Characteristics:

Orphanet epidemiological data:

55
frontometaphyseal dysplasia
Inheritance: X-linked dominant; Prevalence: <1/1000000 (Worldwide); Age of onset: Neonatal;

Classifications:



Summaries for Frontometaphyseal Dysplasia

NIH Rare Diseases : 49 Frontometaphyseal dysplasia (FMD) is a genetic disorder characterized by abnormalities in skeletal development and problems in other organs of the body. It is part of a group of diseases called otopalatodigital spectrum disorders, which also includes otopalatodigital syndrome type 1, otopalatodigital syndrome type 2, and Melnick-Needles syndrome. In general, these disorders involve hearing loss (due to  malformations in the tiny bones in the ears (ossicles)), cleft roof of the mouth (palate), and defects of the bones in the fingers and/or toes (digits). Frontometaphyseal dysplasia is distinguished from the other diseases of the group by the presence of joint deformities (contractures) that restrict the movement of certain joints. Other symptoms may include prominent brow ridges; wide-set and downward-slanting eyes; a very small lower jaw and chin (micrognathia); small, missing or misaligned teeth; bowed limbs; an abnormal curvature of the spine (scoliosis); obstruction of ureters; heart defects; and breathing problems. Males generally have more severe features than females. FMD is caused by mutations in the FLNA gene. Inheritance is X-linked. There is also a form of FMD caused by mutations in the  gene MAP3K7 with is known as frontometaphyseal dysplasia 2 and it is is inherited in an autosomal dominant manner. Treatment depends on the problems present and may include hearing aid and surgery to correct the facial findings and the bone defects. Last updated: 2/6/2017

MalaCards based summary : Frontometaphyseal Dysplasia, also known as fmd, is related to frontometaphyseal dysplasia 2 and frontometaphyseal dysplasia 1, and has symptoms including ureteral stenosis, hydronephrosis and high palate. An important gene associated with Frontometaphyseal Dysplasia is FLNA (Filamin A), and among its related pathways/superpathways are NF-kappaB Signaling and Toll-like receptor signaling pathway. Affiliated tissues include bone, heart and eye, and related phenotype is Synthetic lethal with gemcitabine.

Genetics Home Reference : 24 Frontometaphyseal dysplasia is a disorder involving abnormalities in skeletal development and other health problems. It is a member of a group of related conditions called otopalatodigital spectrum disorders, which also includes otopalatodigital syndrome type 1, otopalatodigital syndrome type 2, and Melnick-Needles syndrome. In general, these disorders involve hearing loss caused by malformations in the tiny bones in the ears (ossicles), problems in the development of the roof of the mouth (palate), and skeletal abnormalities involving the fingers and/or toes (digits).

Related Diseases for Frontometaphyseal Dysplasia

Diseases in the Frontometaphyseal Dysplasia family:

Frontometaphyseal Dysplasia 1 Frontometaphyseal Dysplasia 2

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

(show all 20)
# Related Disease Score Top Affiliating Genes
1 frontometaphyseal dysplasia 2 12.4
2 frontometaphyseal dysplasia 1 12.3
3 fibromuscular dysplasia 12.0
4 otopalatodigital syndrome, type i 11.6
5 melnick-needles syndrome 11.5
6 otopalatodigital syndrome, type ii 11.3
7 cohen syndrome 10.1
8 otopalatodigital syndrome 10.1
9 craniometaphyseal dysplasia, autosomal dominant 9.9
10 keloid formation 9.9
11 pyle disease 9.9
12 orthostatic intolerance 9.9
13 keloids 9.9
14 periventricular nodular heterotopia 9.9
15 scoliosis 9.9
16 tracheal stenosis 9.9
17 cerebritis 9.9
18 chiari malformation 9.9
19 aneurysm 9.9
20 cerebral aneurysms 9.9

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



Diseases related to Frontometaphyseal Dysplasia

Symptoms & Phenotypes for Frontometaphyseal Dysplasia

Human phenotypes related to Frontometaphyseal Dysplasia:

55 31 (show all 37)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 ureteral stenosis 55 31 occasional (7.5%) Occasional (29-5%) HP:0000071
2 hydronephrosis 55 31 occasional (7.5%) Occasional (29-5%) HP:0000126
3 high palate 55 31 frequent (33%) Frequent (79-30%) HP:0000218
4 hypertelorism 55 31 hallmark (90%) Very frequent (99-80%) HP:0000316
5 prominent supraorbital ridges 55 31 hallmark (90%) Very frequent (99-80%) HP:0000336
6 micrognathia 55 31 hallmark (90%) Very frequent (99-80%) HP:0000347
7 conductive hearing impairment 55 31 hallmark (90%) Very frequent (99-80%) HP:0000405
8 sensorineural hearing impairment 55 31 hallmark (90%) Very frequent (99-80%) HP:0000407
9 downslanted palpebral fissures 55 31 hallmark (90%) Very frequent (99-80%) HP:0000494
10 abnormality of the metaphysis 55 31 hallmark (90%) Very frequent (99-80%) HP:0000944
11 craniosynostosis 55 31 occasional (7.5%) Occasional (29-5%) HP:0001363
12 joint stiffness 55 31 hallmark (90%) Very frequent (99-80%) HP:0001387
13 subglottic stenosis 55 31 occasional (7.5%) Occasional (29-5%) HP:0001607
14 scoliosis 55 31 frequent (33%) Frequent (79-30%) HP:0002650
15 tracheal stenosis 55 31 occasional (7.5%) Occasional (29-5%) HP:0002777
16 fused cervical vertebrae 55 31 frequent (33%) Frequent (79-30%) HP:0002949
17 elbow dislocation 55 31 frequent (33%) Frequent (79-30%) HP:0003042
18 abnormal form of the vertebral bodies 55 31 frequent (33%) Frequent (79-30%) HP:0003312
19 craniofacial hyperostosis 55 31 hallmark (90%) Very frequent (99-80%) HP:0004493
20 synostosis of carpal bones 55 31 frequent (33%) Frequent (79-30%) HP:0005048
21 absent/hypoplastic paranasal sinuses 55 31 hallmark (90%) Very frequent (99-80%) HP:0005453
22 accelerated skeletal maturation 55 31 frequent (33%) Frequent (79-30%) HP:0005616
23 irregular metacarpals 55 31 frequent (33%) Frequent (79-30%) HP:0006160
24 abnormality of dental morphology 55 31 hallmark (90%) Very frequent (99-80%) HP:0006482
25 bowing of the long bones 55 31 hallmark (90%) Very frequent (99-80%) HP:0006487
26 atrioventricular canal defect 55 31 occasional (7.5%) Occasional (29-5%) HP:0006695
27 posterior vertebral hypoplasia 55 31 frequent (33%) Frequent (79-30%) HP:0008451
28 urethral stenosis 55 31 occasional (7.5%) Occasional (29-5%) HP:0008661
29 hypoplasia of the musculature 55 31 frequent (33%) Frequent (79-30%) HP:0009004
30 ulnar deviation of finger 55 31 frequent (33%) Frequent (79-30%) HP:0009465
31 short distal phalanx of the thumb 55 31 frequent (33%) Frequent (79-30%) HP:0009650
32 reduced number of teeth 55 31 hallmark (90%) Very frequent (99-80%) HP:0009804
33 short distal phalanx of hallux 55 31 frequent (33%) Frequent (79-30%) HP:0010103
34 long metacarpals 55 31 frequent (33%) Frequent (79-30%) HP:0010493
35 camptodactyly of finger 55 31 hallmark (90%) Very frequent (99-80%) HP:0100490
36 long fingers 55 31 frequent (33%) Frequent (79-30%) HP:0100807
37 abnormal diaphysis morphology 55 Very frequent (99-80%)

GenomeRNAi Phenotypes related to Frontometaphyseal Dysplasia according to GeneCards Suite gene sharing:

25
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Synthetic lethal with gemcitabine GR00225-A 8.62 MAP3K7 TAB2

Drugs & Therapeutics for Frontometaphyseal Dysplasia

Search Clinical Trials , NIH Clinical Center for Frontometaphyseal Dysplasia

Genetic Tests for Frontometaphyseal Dysplasia

Genetic tests related to Frontometaphyseal Dysplasia:

# Genetic test Affiliating Genes
1 Frontometaphyseal Dysplasia 28 FLNA

Anatomical Context for Frontometaphyseal Dysplasia

MalaCards organs/tissues related to Frontometaphyseal Dysplasia:

38
Bone, Heart, Eye

Publications for Frontometaphyseal Dysplasia

Articles related to Frontometaphyseal Dysplasia:

(show all 37)
# Title Authors Year
1
Structural and thermodynamic basis of a frontometaphyseal dysplasia mutation in filamin A. ( 28348077 )
2017
2
Autosomal dominant frontometaphyseal dysplasia: Delineation of the clinical phenotype. ( 28498505 )
2017
3
Mutations in MAP3K7 that Alter the Activity of the TAK1 Signaling Complex Cause Frontometaphyseal Dysplasia. ( 27426733 )
2016
4
Recurrence of frontometaphyseal dysplasia in two sisters with a mutation in FLNA and an atypical paternal phenotype: Insights into genotype-phenotype correlation. ( 25820619 )
2015
5
Frontometaphyseal dysplasia and keloid formation without FLNA mutations. ( 25899317 )
2015
6
Airway management of a child with frontometaphyseal dysplasia (Gorlin Cohen syndrome). ( 24803775 )
2014
7
Otopalatodigital syndrome spectrum disorders: otopalatodigital syndrome types 1 and 2, frontometaphyseal dysplasia and Melnick-Needles syndrome. ( 16926860 )
2007
8
Frontometaphyseal dysplasia: mutations in FLNA and phenotypic diversity. ( 16835913 )
2006
9
Genotype-epigenotype-phenotype correlations in females with frontometaphyseal dysplasia. ( 16596676 )
2006
10
A new three-generational family with frontometaphyseal dysplasia, male-to-female transmission, and a previously reported FLNA mutation. ( 15523633 )
2005
11
A dual phenotype of periventricular nodular heterotopia and frontometaphyseal dysplasia in one patient caused by a single FLNA mutation leading to two functionally different aberrant transcripts. ( 14988809 )
2004
12
Clinical and genetic heterogeneity in frontometaphyseal dysplasia: severe progressive scoliosis in two families. ( 12503106 )
2003
13
Frontometaphyseal dysplasia: patient with ruptured aneurysm of the aortic sinus of Valsalva and cerebral aneurysms. ( 11891696 )
2002
14
Otopalatodigital syndrome and frontometaphyseal dysplasia, splitters and lumpers, and paternity of ideas. ( 11074503 )
2000
15
Foot deformity in frontometaphyseal dysplasia (Gorlin-Cohen syndrome): a case report. ( 10789105 )
2000
16
Fronto-otopalatodigital osteodysplasia: clinical evidence for a single entity encompassing Melnick-Needles syndrome, otopalatodigital syndrome types 1 and 2, and frontometaphyseal dysplasia. ( 10706363 )
2000
17
Frontometaphyseal dysplasia: a case with Arnold-Chiari malformation and bracket epiphysis of the first metacarpal bone. ( 10221024 )
1999
18
Cranioplasty in frontometaphyseal dysplasia. ( 9734434 )
1998
19
CT and MR findings in frontometaphyseal dysplasia. ( 9071288 )
1997
20
Frontometaphyseal dysplasia: neonatal radiographic diagnosis. ( 7645585 )
1995
21
Radiological changes of frontometaphyseal dysplasia in the neonate. ( 8577509 )
1995
22
Restrictive chest bellows disease and frontometaphyseal dysplasia. ( 8131478 )
1993
23
Sibs with mental retardation, supraorbital sclerosis, and metaphyseal dysplasia: frontometaphyseal dysplasia, craniometaphyseal dysplasia, or a new syndrome? ( 1956063 )
1991
24
The anaesthetic management of an infant with frontometaphyseal dysplasia (Gorlin-Cohen syndrome). ( 3176838 )
1988
25
Laryngo-tracheal stenosis in frontometaphyseal dysplasia. ( 3343570 )
1988
26
Mitral valve prolapse in a patient with frontometaphyseal dysplasia. ( 3742931 )
1986
27
Frontometaphyseal dysplasia: symptoms and possible mode of inheritance. ( 6593448 )
1984
28
Picture of the month: Frontometaphyseal dysplasia. ( 6613928 )
1983
29
Frontometaphyseal dysplasia: autosomal dominant or X-linked? ( 7189217 )
1980
30
Frontometaphyseal dysplasia--evidence for X-linked inheritance. ( 7395904 )
1980
31
Frontometaphyseal dysplasia with congenital urinary tract malformations. ( 527247 )
1979
32
Frontometaphyseal Dysplasia. Evidence for dominant inheritance. ( 1258835 )
1976
33
Frontometaphyseal dysplasia: evidence for autosomal dominant inheritance. ( 998829 )
1976
34
Familial frontometaphyseal dysplasia- evidence for dominant inheritance. ( 1218235 )
1975
35
Frontometaphyseal dysplasia: a progressive disease of bone and connective tissue. ( 4282264 )
1974
36
Frontometaphyseal dysplasia. ( 5044403 )
1972
37
Frontometaphyseal dysplasia. A new syndrome. ( 5807657 )
1969

Variations for Frontometaphyseal Dysplasia

ClinVar genetic disease variations for Frontometaphyseal Dysplasia:

6
# Gene Variation Type Significance SNP ID Assembly Location
1 FLNA NM_001110556.1(FLNA): c.3476A> C (p.Asp1159Ala) single nucleotide variant Pathogenic rs28935471 GRCh37 Chromosome X, 153588687: 153588687
2 FLNA NM_001110556.1(FLNA): c.3557C> T (p.Ser1186Leu) single nucleotide variant Pathogenic/Likely pathogenic rs137853312 GRCh37 Chromosome X, 153588606: 153588606
3 FLNA NM_001456.3(FLNA): c.3668C> T (p.Pro1223Leu) single nucleotide variant Pathogenic rs1060500716 GRCh38 Chromosome X, 154360127: 154360127
4 FLNA NM_001456.3(FLNA): c.5964_5965delCT (p.Cys1989Phefs) deletion Pathogenic rs1060500718 GRCh38 Chromosome X, 154353329: 154353330
5 FLNA NM_001456.3(FLNA): c.4143-1G> T single nucleotide variant Likely pathogenic GRCh38 Chromosome X, 154359407: 154359407
6 FLNA NM_001456.3(FLNA): c.4840_4852delGGTCGCTACACCA (p.Gly1614Serfs) deletion Pathogenic GRCh38 Chromosome X, 154357527: 154357539
7 FLNA NM_001110556.1(FLNA): c.999_1008dup (p.Asp337Argfs) duplication Pathogenic GRCh37 Chromosome X, 153594987: 153594996
8 FLNA NM_001456.3(FLNA): c.4596_4598+5del deletion Likely pathogenic GRCh38 Chromosome X, 154358440: 154358447

Expression for Frontometaphyseal Dysplasia

Search GEO for disease gene expression data for Frontometaphyseal Dysplasia.

Pathways for Frontometaphyseal Dysplasia

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

(show all 26)
# Super pathways Score Top Affiliating Genes
1 12.14 MAP3K7 TAB2
2
Show member pathways
12.11 MAP3K7 TAB2
3
Show member pathways
12.08 MAP3K7 TAB2
4
Show member pathways
12.02 MAP3K7 TAB2
5
Show member pathways
12.02 MAP3K7 TAB2
6
Show member pathways
12.01 MAP3K7 TAB2
7 11.99 FLNA MAP3K7 TAB2
8
Show member pathways
11.93 MAP3K7 TAB2
9
Show member pathways
11.93 MAP3K7 TAB2
10
Show member pathways
11.91 MAP3K7 TAB2
11
Show member pathways
11.9 MAP3K7 TAB2
12
Show member pathways
11.87 MAP3K7 TAB2
13 11.86 MAP3K7 TAB2
14
Show member pathways
11.85 MAP3K7 TAB2
15
Show member pathways
11.8 MAP3K7 TAB2
16
Show member pathways
11.78 MAP3K7 TAB2
17
Show member pathways
11.77 MAP3K7 TAB2
18 11.75 MAP3K7 TAB2
19
Show member pathways
11.67 MAP3K7 TAB2
20 11.54 MAP3K7 TAB2
21
Show member pathways
11.46 MAP3K7 TAB2
22 11.42 MAP3K7 TAB2
23 11.36 MAP3K7 TAB2
24 11.23 MAP3K7 TAB2
25 10.42 MAP3K7 TAB2
26 10.28 FLNA MAP3K7 TAB2

GO Terms for Frontometaphyseal Dysplasia

Cellular components related to Frontometaphyseal Dysplasia according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 endosome membrane GO:0010008 8.62 MAP3K7 TAB2

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

(show all 11)
# Name GO ID Score Top Affiliating Genes
1 Fc-epsilon receptor signaling pathway GO:0038095 9.49 MAP3K7 TAB2
2 T cell receptor signaling pathway GO:0050852 9.48 MAP3K7 TAB2
3 positive regulation of NF-kappaB transcription factor activity GO:0051092 9.46 MAP3K7 TAB2
4 stimulatory C-type lectin receptor signaling pathway GO:0002223 9.43 MAP3K7 TAB2
5 activation of MAPK activity GO:0000187 9.4 MAP3K7 TAB2
6 I-kappaB kinase/NF-kappaB signaling GO:0007249 9.37 MAP3K7 TAB2
7 JNK cascade GO:0007254 9.32 MAP3K7 TAB2
8 MyD88-dependent toll-like receptor signaling pathway GO:0002755 9.26 MAP3K7 TAB2
9 MyD88-independent toll-like receptor signaling pathway GO:0002756 9.16 MAP3K7 TAB2
10 nucleotide-binding oligomerization domain containing signaling pathway GO:0070423 8.96 MAP3K7 TAB2
11 positive regulation of I-kappaB kinase/NF-kappaB signaling GO:0043123 8.8 FLNA MAP3K7 TAB2

Sources for Frontometaphyseal Dysplasia

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
27 GO
28 GTR
29 HGMD
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 MedGen
41 MeSH
42 MESH via Orphanet
43 MGI
45 NCI
46 NCIt
47 NDF-RT
50 NINDS
51 Novoseek
53 OMIM
54 OMIM via Orphanet
58 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
Content
Loading form....