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 50 24 25 56 29 13 52 69
Fmd 24 25

Characteristics:

Orphanet epidemiological data:

56
frontometaphyseal dysplasia
Inheritance: X-linked dominant; Prevalence: <1/1000000 (Worldwide); Age of onset: Neonatal;

Classifications:



Summaries for Frontometaphyseal Dysplasia

NIH Rare Diseases : 50 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. it is caused by mutations in the flna gene. inheritance is x-linked. 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 Development FGFR signaling pathway. Affiliated tissues include bone, heart and eye, and related phenotype is Synthetic lethal with gemcitabine.

Genetics Home Reference : 25 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 2 Frontometaphyseal Dysplasia 1

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

(show all 18)
id Related Disease Score Top Affiliating Genes
1 frontometaphyseal dysplasia 2 12.3
2 frontometaphyseal dysplasia 1 12.2
3 fibromuscular dysplasia 11.9
4 melnick-needles syndrome 11.4
5 otopalatodigital syndrome, type i 11.2
6 otopalatodigital syndrome, type ii 11.1
7 otopalatodigital syndrome 10.0
8 cohen syndrome 10.0
9 tracheal stenosis 9.8
10 cerebritis 9.8
11 chiari malformation 9.8
12 keloid formation 9.8
13 aneurysm 9.8
14 cerebral aneurysms 9.8
15 craniometaphyseal dysplasia 9.8
16 keloids 9.8
17 scoliosis 9.8
18 frontonasal dysplasia with alopecia and genital anomaly 8.9 FLNA MAP3K7 TAB2

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:

56 32 (show all 38)
id Description HPO Frequency Orphanet Frequency HPO Source Accession
1 ureteral stenosis 56 32 occasional (7.5%) Occasional (29-5%) HP:0000071
2 hydronephrosis 56 32 occasional (7.5%) Occasional (29-5%) HP:0000126
3 high palate 56 32 frequent (33%) Frequent (79-30%) HP:0000218
4 hypertelorism 56 32 hallmark (90%) Very frequent (99-80%) HP:0000316
5 prominent supraorbital ridges 56 32 hallmark (90%) Very frequent (99-80%) HP:0000336
6 micrognathia 56 32 hallmark (90%) Very frequent (99-80%) HP:0000347
7 conductive hearing impairment 56 32 hallmark (90%) Very frequent (99-80%) HP:0000405
8 sensorineural hearing impairment 56 32 hallmark (90%) Very frequent (99-80%) HP:0000407
9 downslanted palpebral fissures 56 32 hallmark (90%) Very frequent (99-80%) HP:0000494
10 craniosynostosis 56 32 occasional (7.5%) Occasional (29-5%) HP:0001363
11 joint stiffness 56 32 hallmark (90%) Very frequent (99-80%) HP:0001387
12 subglottic stenosis 56 32 occasional (7.5%) Occasional (29-5%) HP:0001607
13 scoliosis 56 32 frequent (33%) Frequent (79-30%) HP:0002650
14 tracheal stenosis 56 32 occasional (7.5%) Occasional (29-5%) HP:0002777
15 fused cervical vertebrae 56 32 frequent (33%) Frequent (79-30%) HP:0002949
16 elbow dislocation 56 32 frequent (33%) Frequent (79-30%) HP:0003042
17 abnormal form of the vertebral bodies 56 32 frequent (33%) Frequent (79-30%) HP:0003312
18 craniofacial hyperostosis 56 32 hallmark (90%) Very frequent (99-80%) HP:0004493
19 synostosis of carpal bones 56 32 frequent (33%) Frequent (79-30%) HP:0005048
20 absent/hypoplastic paranasal sinuses 56 32 hallmark (90%) Very frequent (99-80%) HP:0005453
21 accelerated skeletal maturation 56 32 frequent (33%) Frequent (79-30%) HP:0005616
22 irregular metacarpals 56 32 frequent (33%) Frequent (79-30%) HP:0006160
23 abnormality of dental morphology 56 32 hallmark (90%) Very frequent (99-80%) HP:0006482
24 bowing of the long bones 56 32 hallmark (90%) Very frequent (99-80%) HP:0006487
25 atrioventricular canal defect 56 32 occasional (7.5%) Occasional (29-5%) HP:0006695
26 posterior vertebral hypoplasia 56 32 frequent (33%) Frequent (79-30%) HP:0008451
27 urethral stenosis 56 32 occasional (7.5%) Occasional (29-5%) HP:0008661
28 hypoplasia of the musculature 56 32 frequent (33%) Frequent (79-30%) HP:0009004
29 ulnar deviation of finger 56 32 frequent (33%) Frequent (79-30%) HP:0009465
30 short distal phalanx of the thumb 56 32 frequent (33%) Frequent (79-30%) HP:0009650
31 reduced number of teeth 56 32 hallmark (90%) Very frequent (99-80%) HP:0009804
32 short distal phalanx of hallux 56 32 frequent (33%) Frequent (79-30%) HP:0010103
33 long metacarpals 56 32 frequent (33%) Frequent (79-30%) HP:0010493
34 camptodactyly of finger 56 32 hallmark (90%) Very frequent (99-80%) HP:0100490
35 long fingers 56 32 frequent (33%) Frequent (79-30%) HP:0100807
36 abnormal diaphysis morphology 56 Very frequent (99-80%)
37 abnormality of the metaphyses 56 Very frequent (99-80%)
38 abnormality of the metaphysis 32 hallmark (90%) HP:0000944

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

26
id 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:

id Genetic test Affiliating Genes
1 Frontometaphyseal Dysplasia 29 24 FLNA

Anatomical Context for Frontometaphyseal Dysplasia

MalaCards organs/tissues related to Frontometaphyseal Dysplasia:

39
Bone, Heart, Eye

Publications for Frontometaphyseal Dysplasia

Articles related to Frontometaphyseal Dysplasia:

(show all 37)
id 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
Frontometaphyseal dysplasia and keloid formation without FLNA mutations. ( 25899317 )
2015
5
Recurrence of frontometaphyseal dysplasia in two sisters with a mutation in FLNA and an atypical paternal phenotype: Insights into genotype-phenotype correlation. ( 25820619 )
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
Genotype-epigenotype-phenotype correlations in females with frontometaphyseal dysplasia. ( 16596676 )
2006
9
Frontometaphyseal dysplasia: mutations in FLNA and phenotypic diversity. ( 16835913 )
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
Fronto-otopalatodigital osteodysplasia: clinical evidence for a single entity encompassing Melnick-Needles syndrome, otopalatodigital syndrome types 1 and 2, and frontometaphyseal dysplasia. ( 10706363 )
2000
15
Otopalatodigital syndrome and frontometaphyseal dysplasia, splitters and lumpers, and paternity of ideas. ( 11074503 )
2000
16
Foot deformity in frontometaphyseal dysplasia (Gorlin-Cohen syndrome): a case report. ( 10789105 )
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
Radiological changes of frontometaphyseal dysplasia in the neonate. ( 8577509 )
1995
21
Frontometaphyseal dysplasia: neonatal radiographic diagnosis. ( 7645585 )
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 autosomal dominant inheritance. ( 998829 )
1976
33
Frontometaphyseal Dysplasia. Evidence for dominant inheritance. ( 1258835 )
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
id 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

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 22)
id Super pathways Score Top Affiliating Genes
1 12.1 MAP3K7 TAB2
2
Show member pathways
12.01 MAP3K7 TAB2
3
Show member pathways
12 MAP3K7 TAB2
4
Show member pathways
11.99 MAP3K7 TAB2
5
Show member pathways
11.99 MAP3K7 TAB2
6 11.96 FLNA MAP3K7 TAB2
7
Show member pathways
11.92 MAP3K7 TAB2
8
Show member pathways
11.89 MAP3K7 TAB2
9
Show member pathways
11.88 MAP3K7 TAB2
10
Show member pathways
11.85 MAP3K7 TAB2
11 11.83 MAP3K7 TAB2
12
Show member pathways
11.78 MAP3K7 TAB2
13
Show member pathways
11.77 MAP3K7 TAB2
14 11.75 MAP3K7 TAB2
15
Show member pathways
11.67 MAP3K7 TAB2
16 11.54 MAP3K7 TAB2
17
Show member pathways
11.46 MAP3K7 TAB2
18 11.4 MAP3K7 TAB2
19 11.36 MAP3K7 TAB2
20 11.23 MAP3K7 TAB2
21 10.42 MAP3K7 TAB2
22 10.28 FLNA MAP3K7 TAB2

GO Terms for Frontometaphyseal Dysplasia

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

id 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:

id Name GO ID Score Top Affiliating Genes
1 Fc-epsilon receptor signaling pathway GO:0038095 9.48 MAP3K7 TAB2
2 T cell receptor signaling pathway GO:0050852 9.46 MAP3K7 TAB2
3 positive regulation of NF-kappaB transcription factor activity GO:0051092 9.43 MAP3K7 TAB2
4 stimulatory C-type lectin receptor signaling pathway GO:0002223 9.4 MAP3K7 TAB2
5 activation of MAPK activity GO:0000187 9.37 MAP3K7 TAB2
6 I-kappaB kinase/NF-kappaB signaling GO:0007249 9.32 MAP3K7 TAB2
7 JNK cascade GO:0007254 9.26 MAP3K7 TAB2
8 MyD88-dependent toll-like receptor signaling pathway GO:0002755 9.16 MAP3K7 TAB2
9 nucleotide-binding oligomerization domain containing signaling pathway GO:0070423 8.96 MAP3K7 TAB2
10 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
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 MedGen
42 MeSH
43 MESH via Orphanet
44 MGI
46 NCI
47 NCIt
48 NDF-RT
51 NINDS
52 Novoseek
54 OMIM
55 OMIM via Orphanet
59 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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