FMD1
MCID: FRN049
MIFTS: 36

Frontometaphyseal Dysplasia 1 (FMD1)

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

Aliases & Classifications for Frontometaphyseal Dysplasia 1

MalaCards integrated aliases for Frontometaphyseal Dysplasia 1:

Name: Frontometaphyseal Dysplasia 1 56 73
Fmd1 56 73
Fmd 56 73

Characteristics:

OMIM:

56
Inheritance:
x-linked recessive

Miscellaneous:
otopalatodigital syndrome type ii (opd2, ) is an allelic disorder
melnick-needles syndrome (mns, ) is an allelic disorder
periventricular heterotopia is an allelic disorder
variable expression in females otopalatodigital syndrome type i (opd1, ) is an allelic disorder


HPO:

31
frontometaphyseal dysplasia 1:
Inheritance x-linked recessive inheritance


Classifications:



Summaries for Frontometaphyseal Dysplasia 1

OMIM : 56 Frontometaphyseal dysplasia-1 is 1 of 4 otopalatodigital syndromes caused by mutations in the FLNA gene. The disorders, which include otopalatodigital syndrome-1 (OPD1; 311300), otopalatodigital syndrome-2 (OPD2; 304120), and Melnick-Needles syndrome (MNS; 309350), constitute a phenotypic spectrum. At the mild end of the spectrum, males with OPD1 have cleft palate and mild skeletal anomalies with conductive deafness caused by ossicular anomalies. FMD1 is characterized by a generalized skeletal dysplasia, deafness, and urogenital defects. Males with OPD2 have disabling skeletal anomalies in addition to variable malformations in the hindbrain, heart, intestines, and kidneys that frequently lead to perinatal death. The most severe phenotype, MNS, is characterized by a skeletal dysplasia in the heterozygote. Affected males exhibit severe malformations similar to those observed in individuals with OPD2, resulting in prenatal lethality or death in the first few months of life (review by Robertson, 2005). Verloes et al. (2000) suggested that these disorders constitute a single entity, which they termed 'frontootopalatodigital osteodysplasia.' (305620)

MalaCards based summary : Frontometaphyseal Dysplasia 1, also known as fmd1, is related to frontometaphyseal dysplasia and melnick-needles syndrome. An important gene associated with Frontometaphyseal Dysplasia 1 is FLNA (Filamin A). Affiliated tissues include heart, kidney and bone, and related phenotypes are hypertelorism and genu valgum

UniProtKB/Swiss-Prot : 73 Frontometaphyseal dysplasia 1: An X-linked disease characterized by generalized skeletal dysplasia, deafness, and urogenital defects.

Related Diseases for Frontometaphyseal Dysplasia 1

Diseases in the Frontometaphyseal Dysplasia family:

Frontometaphyseal Dysplasia 1 Frontometaphyseal Dysplasia 2

Diseases related to Frontometaphyseal Dysplasia 1 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 41)
# Related Disease Score Top Affiliating Genes
1 frontometaphyseal dysplasia 32.5 LOC107988032 FLNA
2 melnick-needles syndrome 31.1 LOC107988032 FLNA
3 fibromuscular dysplasia 12.4
4 otopalatodigital syndrome, type i 11.4
5 facioscapulohumeral muscular dystrophy 1 11.4
6 otopalatodigital syndrome, type ii 11.3
7 coronary artery dissection, spontaneous 11.2
8 frontometaphyseal dysplasia 2 11.2
9 mouth disease 11.1
10 47,xyy 10.3
11 arteries, anomalies of 10.2
12 hyperlipoproteinemia, type iii 10.2
13 coronary artery anomaly 10.2
14 ischemia 10.2
15 heart valve disease 10.2
16 anthrax disease 10.2
17 cytokine deficiency 10.2
18 aneurysm 10.2
19 atrial standstill 1 10.0
20 hypertriglyceridemia, familial 10.0
21 systemic lupus erythematosus 10.0
22 ocular motor apraxia 10.0
23 body mass index quantitative trait locus 1 10.0
24 follicular lymphoma 10.0
25 mastitis 10.0
26 rabies 10.0
27 urticaria 10.0
28 renovascular hypertension 10.0
29 vascular disease 10.0
30 arteriosclerosis 10.0
31 movement disease 10.0
32 myocarditis 10.0
33 keratoconjunctivitis 10.0
34 reversible cerebral vasoconstriction syndrome 10.0
35 raynaud phenomenon 10.0
36 intestinal pseudoobstruction, neuronal, chronic idiopathic, x-linked 9.6 LOC107988032 FLNA
37 periventricular nodular heterotopia 1 9.6 LOC107988032 FLNA
38 periventricular nodular heterotopia 9.6 LOC107988032 FLNA
39 type i ehlers-danlos syndrome 9.5 LOC107988032 FLNA
40 fg syndrome 2 9.5 LOC107988032 FLNA
41 terminal osseous dysplasia 9.2 LOC107988032 FLNA

Graphical network of the top 20 diseases related to Frontometaphyseal Dysplasia 1:



Diseases related to Frontometaphyseal Dysplasia 1

Symptoms & Phenotypes for Frontometaphyseal Dysplasia 1

Human phenotypes related to Frontometaphyseal Dysplasia 1:

31 (show all 42)
# Description HPO Frequency HPO Source Accession
1 hypertelorism 31 HP:0000316
2 genu valgum 31 HP:0002857
3 intellectual disability 31 HP:0001249
4 scoliosis 31 HP:0002650
5 high palate 31 HP:0000218
6 coarse facial features 31 HP:0000280
7 prominent supraorbital ridges 31 HP:0000336
8 dental malocclusion 31 HP:0000689
9 wide nasal bridge 31 HP:0000431
10 downslanted palpebral fissures 31 HP:0000494
11 sensorineural hearing impairment 31 HP:0000407
12 skeletal muscle atrophy 31 HP:0003202
13 delayed eruption of teeth 31 HP:0000684
14 coxa valga 31 HP:0002673
15 elbow flexion contracture 31 HP:0002987
16 scapular winging 31 HP:0003691
17 mitral valve prolapse 31 HP:0001634
18 short chin 31 HP:0000331
19 hydronephrosis 31 HP:0000126
20 arachnodactyly 31 HP:0001166
21 pointed chin 31 HP:0000307
22 camptodactyly of finger 31 HP:0100490
23 wrist flexion contracture 31 HP:0001239
24 hydroureter 31 HP:0000072
25 knee flexion contracture 31 HP:0006380
26 stridor 31 HP:0010307
27 fused cervical vertebrae 31 HP:0002949
28 persistence of primary teeth 31 HP:0006335
29 hirsutism 31 HP:0001007
30 selective tooth agenesis 31 HP:0001592
31 long foot 31 HP:0001833
32 coat hanger sign of ribs 31 HP:0006665
33 anteriorly placed odontoid process 31 HP:0004608
34 broad phalanges of the hand 31 HP:0009768
35 large foramen magnum 31 HP:0002700
36 cor pulmonale 31 HP:0001648
37 ankle flexion contracture 31 HP:0006466
38 antegonial notching of mandible 31 HP:0003779
39 long phalanx of finger 31 HP:0006155
40 partial fusion of carpals 31 HP:0006207
41 increased density of long bone diaphyses 31 HP:0006440
42 partial fusion of tarsals 31 HP:0008097

Symptoms via clinical synopsis from OMIM:

56
Head And Neck Eyes:
hypertelorism
downslanting palpebral fissures

Skeletal Spine:
scoliosis
anteriorly placed odontoid process
wide interpedicular distance
cervical vertebral fusion

Head And Neck Face:
prominent supraorbital ridges
coarse facies
small pointed chin

Skeletal Pelvis:
coxa valga
flared pelvis

Genitourinary Kidneys:
hydronephrosis

Genitourinary Ureters:
hydroureter

Respiratory Lung:
cor pulmonale

Skeletal Feet:
partial fusion of tarsals
large feet

Chest Ribs Sternum Clavicles And Scapulae:
winged scapulae
irregular rib contours
"coat hanger" deformity of lower ribs

Head And Neck Ears:
progressive mixed conductive and sensorineural hearing loss

Muscle Soft Tissue:
muscle wasting (especially legs and arms)

Skeletal Limbs:
genu valgum
increased density of long bone diaphyses
elbow contractures
knee and ankle contractures
erlenmeyer-flask appearance of femur and tibia

Head And Neck Mouth:
high palate

Head And Neck Nose:
wide nasal bridge

Cardiovascular Heart:
mitral valve prolapse

Skeletal Hands:
arachnodactyly
partial fusion of carpals
finger and wrist contractures
wide and elongated phalanges

Head And Neck Teeth:
selective tooth agenesis
malocclusion
delayed tooth eruption
retained deciduous teeth

Skeletal Skull:
antegonial notching of mandible
incomplete sinus development
wide foramen magnum
hypoplastic condyloid process

Neurologic Central Nervous System:
mental retardation

Respiratory Airways:
congenital stridor
subglottic tracheal narrowing

Skin Nails Hair Hair:
hirsutism of buttocks and thighs

Clinical features from OMIM:

305620

Drugs & Therapeutics for Frontometaphyseal Dysplasia 1

Search Clinical Trials , NIH Clinical Center for Frontometaphyseal Dysplasia 1

Genetic Tests for Frontometaphyseal Dysplasia 1

Anatomical Context for Frontometaphyseal Dysplasia 1

MalaCards organs/tissues related to Frontometaphyseal Dysplasia 1:

40
Heart, Kidney, Bone, Skeletal Muscle, Lung, Endothelial

Publications for Frontometaphyseal Dysplasia 1

Articles related to Frontometaphyseal Dysplasia 1:

(show all 25)
# Title Authors PMID Year
1
A new three-generational family with frontometaphyseal dysplasia, male-to-female transmission, and a previously reported FLNA mutation. 56 6
15523633 2005
2
X-Linked Otopalatodigital Spectrum Disorders 61 6
20301567 2005
3
Frontometaphyseal dysplasia: mutations in FLNA and phenotypic diversity. 56
16835913 2006
4
Genotype-epigenotype-phenotype correlations in females with frontometaphyseal dysplasia. 6
16596676 2006
5
Filamin A: phenotypic diversity. 6
15917206 2005
6
Localized mutations in the gene encoding the cytoskeletal protein filamin A cause diverse malformations in humans. 56
12612583 2003
7
Clinical and genetic heterogeneity in frontometaphyseal dysplasia: severe progressive scoliosis in two families. 56
12503106 2003
8
Fronto-otopalatodigital osteodysplasia: clinical evidence for a single entity encompassing Melnick-Needles syndrome, otopalatodigital syndrome types 1 and 2, and frontometaphyseal dysplasia. 56
10706363 2000
9
Esophageal atresia with distal tracheoesophageal fistula in a patient with fronto-metaphyseal dysplasia. 56
9375915 1997
10
CT and MR findings in frontometaphyseal dysplasia. 6
9071288 1997
11
Frontometaphyseal dysplasia: neonatal radiographic diagnosis. 56
7645585 1995
12
Fronto-metaphyseal dysplasia. Further delineation of the clinical syndrome. 56
7151303 1982
13
Frontometaphyseal dysplasia: autosomal dominant or X-linked? 56
7189217 1980
14
Frontometaphyseal dysplasia--evidence for X-linked inheritance. 56
7395904 1980
15
Frontometaphyseal dysplasia presenting as scoliosis. 56
649644 1978
16
Frontometaphyseal dysplasia: evidence for autosomal dominant inheritance. 56
998829 1976
17
Frontometaphyseal Dysplasia. Evidence for dominant inheritance. 56
1258835 1976
18
[Fronto-metaphyseal dysplasia]. 56
1094899 1975
19
Frontometaphyseal dysplasia. 56
5044403 1972
20
Fronto-metaphyseal dysplasia. A progressive disease of bone and connective tissue. 56
5026209 1972
21
Frontometaphyseal dysplasia. A new syndrome. 56
5807657 1969
22
Genetic investigation of formaldehyde-induced DNA damage response in Schizosaccharomyces pombe. 61
32034465 2020
23
Identification and pathogenicity analysis of Streptococcusequinus FMD1, a beta-hemolytic strain isolated from forest musk deer lung. 61
31902837 2019
24
[Effect of 6-month therapy with perindopril A on structural-functional state of arterial vascular bed in patients with chronic heart failure]. 61
24888193 2014
25
Transient endothelial dysfunction following flow-mediated dilation assessment. 61
21153030 2011

Variations for Frontometaphyseal Dysplasia 1

ClinVar genetic disease variations for Frontometaphyseal Dysplasia 1:

6 (show top 50) (show all 275) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 FLNA NM_001110556.2(FLNA):c.3476A>C (p.Asp1159Ala)SNV Pathogenic 11757 rs28935471 X:153588687-153588687 X:154360319-154360319
2 FLNA NM_001110556.2(FLNA):c.3668C>T (p.Pro1223Leu)SNV Pathogenic 405445 rs1060500716 X:153588495-153588495 X:154360127-154360127
3 FLNA NM_001110556.2(FLNA):c.5988_5989del (p.Cys1997fs)deletion Pathogenic 405447 rs1060500718 X:153581697-153581698 X:154353329-154353330
4 FLNA NM_001110556.2(FLNA):c.4840_4852del (p.Gly1614fs)deletion Pathogenic 464997 rs1557177086 X:153585895-153585907 X:154357527-154357539
5 FLNA NM_001110556.2(FLNA):c.999_1008dup (p.Asp337delinsArgGlnTer)duplication Pathogenic 465027 rs1557179357 X:153594986-153594987 X:154366618-154366619
6 FLNA NM_001110556.2(FLNA):c.3814del (p.Arg1272fs)deletion Pathogenic 533585 rs1557177636 X:153588265-153588265 X:154359897-154359897
7 FLNA NM_001110556.2(FLNA):c.3529G>T (p.Glu1177Ter)SNV Pathogenic 533562 rs1557177738 X:153588634-153588634 X:154360266-154360266
8 FLNA NM_001110556.2(FLNA):c.3865G>T (p.Gly1289Ter)SNV Pathogenic 574177 rs1557177623 X:153588214-153588214 X:154359846-154359846
9 FLNA NM_001110556.2(FLNA):c.5643del (p.Asn1881fs)deletion Pathogenic 575768 rs1569551502 X:153582326-153582326 X:154353958-154353958
10 FLNA NM_001110556.2(FLNA):c.2565+1G>ASNV Pathogenic 575118 rs786205186 X:153590785-153590785 X:154362417-154362417
11 FLNA NM_001110556.2(FLNA):c.5879dup (p.Met1960fs)duplication Pathogenic 647567 X:153581806-153581807 X:154353438-154353439
12 FLNA NM_001110556.2(FLNA):c.7872_7873del (p.Glu2625fs)deletion Pathogenic 652215 X:153577288-153577289 X:154348920-154348921
13 FLNA NM_001110556.2(FLNA):c.3296_3304delinsTCGG (p.Gly1099fs)indel Pathogenic 662513 X:153588859-153588867 X:154360491-154360499
14 FLNA NM_001110556.2(FLNA):c.2452del (p.Ala818fs)deletion Pathogenic 659278 X:153590899-153590899 X:154362531-154362531
15 FLNA NM_001110556.2(FLNA):c.676C>T (p.Arg226Ter)SNV Pathogenic/Likely pathogenic 580826 rs1569551861 X:153596053-153596053 X:154367685-154367685
16 FLNA NM_001110556.2(FLNA):c.3557C>T (p.Ser1186Leu)SNV Pathogenic/Likely pathogenic 11761 rs137853312 X:153588606-153588606 X:154360238-154360238
17 FLNA NM_001110556.2(FLNA):c.4726G>A (p.Gly1576Arg)SNV Pathogenic/Likely pathogenic 209154 rs797045044 X:153586596-153586596 X:154358228-154358228
18 FLNA NM_001110556.2(FLNA):c.4143-1G>TSNV Likely pathogenic 464989 rs1557177485 X:153587775-153587775 X:154359407-154359407
19 FLNA NM_001110556.2(FLNA):c.5686+1G>CSNV Likely pathogenic 533566 rs1557176315 X:153582282-153582282 X:154353914-154353914
20 FLNA NM_001110556.2(FLNA):c.4596_4598+5deldeletion Likely pathogenic 464993 rs1557177279 X:153586808-153586815 X:154358440-154358447
21 FLNA NM_001110556.2(FLNA):c.4142+1G>ASNV Likely pathogenic 662049 X:153587851-153587851 X:154359483-154359483
22 FLNA NM_001110556.2(FLNA):c.2364G>A (p.Glu788=)SNV Conflicting interpretations of pathogenicity 625949 rs1448428046 X:153591069-153591069 X:154362701-154362701
23 FLNA NM_001110556.2(FLNA):c.1138G>A (p.Asp380Asn)SNV Conflicting interpretations of pathogenicity 561301 rs782090266 X:153594766-153594766 X:154366398-154366398
24 FLNA NM_001110556.2(FLNA):c.2974A>G (p.Thr992Ala)SNV Conflicting interpretations of pathogenicity 588552 rs782445995 X:153589909-153589909 X:154361541-154361541
25 FLNA NM_001110556.2(FLNA):c.6217C>T (p.Arg2073Cys)SNV Conflicting interpretations of pathogenicity 465008 rs782069230 X:153581378-153581378 X:154353010-154353010
26 FLNA NM_001110556.2(FLNA):c.3330G>A (p.Ala1110=)SNV Conflicting interpretations of pathogenicity 533605 rs781917512 X:153588833-153588833 X:154360465-154360465
27 FLNA NM_001110556.2(FLNA):c.7779_7780insTTCGGGG (p.Val2594fs)insertion Conflicting interpretations of pathogenicity 453200 rs1557175195 X:153577381-153577382 X:154349013-154349014
28 FLNA NM_001110556.2(FLNA):c.1997C>T (p.Ala666Val)SNV Conflicting interpretations of pathogenicity 405459 rs374295965 X:153592919-153592919 X:154364551-154364551
29 FLNA NM_001110556.2(FLNA):c.7389G>A (p.Ser2463=)SNV Conflicting interpretations of pathogenicity 382810 rs373103712 X:153578180-153578180 X:154349812-154349812
30 FLNA NM_001110556.2(FLNA):c.3036G>A (p.Ser1012=)SNV Conflicting interpretations of pathogenicity 382396 rs373908435 X:153589847-153589847 X:154361479-154361479
31 FLNA NM_001110556.2(FLNA):c.2389G>A (p.Ala797Thr)SNV Conflicting interpretations of pathogenicity 380416 rs201073998 X:153591044-153591044 X:154362676-154362676
32 FLNA NM_001110556.2(FLNA):c.65A>G (p.Asp22Gly)SNV Conflicting interpretations of pathogenicity 391884 rs782598729 X:153599549-153599549 X:154371181-154371181
33 FLNA NM_001110556.2(FLNA):c.4475-4C>TSNV Conflicting interpretations of pathogenicity 391832 rs199652065 X:153586940-153586940 X:154358572-154358572
34 FLNA NM_001110556.2(FLNA):c.3708C>T (p.Gly1236=)SNV Conflicting interpretations of pathogenicity 288752 rs200363918 X:153588455-153588455 X:154360087-154360087
35 FLNA NM_001110556.2(FLNA):c.4420G>A (p.Asp1474Asn)SNV Conflicting interpretations of pathogenicity 195948 rs782129236 X:153587406-153587406 X:154359038-154359038
36 FLNA NM_001110556.2(FLNA):c.1621G>A (p.Glu541Lys)SNV Conflicting interpretations of pathogenicity 213521 rs743546 X:153593574-153593574 X:154365206-154365206
37 FLNA NM_001110556.2(FLNA):c.586C>T (p.Arg196Trp)SNV Conflicting interpretations of pathogenicity 11772 rs137853317 X:153596246-153596246 X:154367878-154367878
38 FLNA NM_001110556.2(FLNA):c.1291G>C (p.Glu431Gln)SNV Conflicting interpretations of pathogenicity 213517 rs781915319 X:153594530-153594530 X:154366162-154366162
39 FLNA NM_001110556.2(FLNA):c.3147C>T (p.Gly1049=)SNV Conflicting interpretations of pathogenicity 93754 rs398123615 X:153589736-153589736 X:154361368-154361368
40 FLNA NM_001110556.2(FLNA):c.4263C>T (p.Thr1421=)SNV Conflicting interpretations of pathogenicity 93759 rs398123618 X:153587654-153587654 X:154359286-154359286
41 FLNA NM_001110556.2(FLNA):c.1439C>T (p.Pro480Leu)SNV Conflicting interpretations of pathogenicity 235716 rs782168634 X:153593845-153593845 X:154365477-154365477
42 FLNA NM_001110556.2(FLNA):c.7394C>T (p.Thr2465Ile)SNV Uncertain significance 239024 rs878854464 X:153578175-153578175 X:154349807-154349807
43 FLNA NM_001110556.2(FLNA):c.7195G>A (p.Val2399Ile)SNV Uncertain significance 239023 rs878854463 X:153578537-153578537 X:154350169-154350169
44 FLNA NM_001110556.2(FLNA):c.2744C>A (p.Thr915Asn)SNV Uncertain significance 239018 rs782045915 X:153590429-153590429 X:154362061-154362061
45 FLNA NM_001110556.2(FLNA):c.1901G>A (p.Arg634His)SNV Uncertain significance 239015 rs782038837 X:153593015-153593015 X:154364647-154364647
46 FLNA NM_001110556.2(FLNA):c.1603G>A (p.Asp535Asn)SNV Uncertain significance 239014 rs782321294 X:153593592-153593592 X:154365224-154365224
47 FLNA NM_001110556.2(FLNA):c.3323G>A (p.Cys1108Tyr)SNV Uncertain significance 93756 rs371677498 X:153588840-153588840 X:154360472-154360472
48 FLNA NM_001110556.2(FLNA):c.569G>A (p.Arg190Gln)SNV Uncertain significance 213491 rs782447567 X:153596263-153596263 X:154367895-154367895
49 FLNA NM_001110556.2(FLNA):c.7059T>G (p.Phe2353Leu)SNV Uncertain significance 220986 rs864622713 X:153579374-153579374 X:154351006-154351006
50 FLNA NM_001110556.2(FLNA):c.1451G>A (p.Arg484Gln)SNV Uncertain significance 213520 rs782371735 X:153593833-153593833 X:154365465-154365465

UniProtKB/Swiss-Prot genetic disease variations for Frontometaphyseal Dysplasia 1:

73
# Symbol AA change Variation ID SNP ID
1 FLNA p.Asp1159Ala VAR_015702 rs28935471
2 FLNA p.Ser1186Leu VAR_015721 rs137853312
3 FLNA p.Gly1728Cys VAR_031312 rs137853316

Expression for Frontometaphyseal Dysplasia 1

Search GEO for disease gene expression data for Frontometaphyseal Dysplasia 1.

Pathways for Frontometaphyseal Dysplasia 1

GO Terms for Frontometaphyseal Dysplasia 1

Sources for Frontometaphyseal Dysplasia 1

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