FMD1
MCID: FRN049
MIFTS: 34

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 57 74
Fmd1 57 74
Fmd 57 74

Characteristics:

OMIM:

57
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:

32
frontometaphyseal dysplasia 1:
Inheritance x-linked recessive inheritance


Classifications:



External Ids:

MeSH 44 D010009

Summaries for Frontometaphyseal Dysplasia 1

OMIM : 57 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 fibromuscular dysplasia and frontometaphyseal dysplasia. 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 : 74 Frontometaphyseal dysplasia 1: An X-linked disease characterized by generalized skeletal dysplasia, deafness, and urogenital defects.

Related Diseases for Frontometaphyseal Dysplasia 1

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:

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

Symptoms via clinical synopsis from OMIM:

57
Head And Neck Eyes:
hypertelorism
downslanting palpebral fissures

Head And Neck Mouth:
high palate

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

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

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:

41
Heart, Kidney, Bone, Skeletal Muscle, Endothelial

Publications for Frontometaphyseal Dysplasia 1

Articles related to Frontometaphyseal Dysplasia 1:

(show all 23)
# Title Authors PMID Year
1
A new three-generational family with frontometaphyseal dysplasia, male-to-female transmission, and a previously reported FLNA mutation. 8 71
15523633 2005
2
Frontometaphyseal dysplasia: mutations in FLNA and phenotypic diversity. 8
16835913 2006
3
Genotype-epigenotype-phenotype correlations in females with frontometaphyseal dysplasia. 71
16596676 2006
4
Otopalatodigital Spectrum Disorders 71
20301567 2005
5
Filamin A: phenotypic diversity. 71
15917206 2005
6
Localized mutations in the gene encoding the cytoskeletal protein filamin A cause diverse malformations in humans. 8
12612583 2003
7
Clinical and genetic heterogeneity in frontometaphyseal dysplasia: severe progressive scoliosis in two families. 8
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. 8
10706363 2000
9
Esophageal atresia with distal tracheoesophageal fistula in a patient with fronto-metaphyseal dysplasia. 8
9375915 1997
10
CT and MR findings in frontometaphyseal dysplasia. 71
9071288 1997
11
Frontometaphyseal dysplasia: neonatal radiographic diagnosis. 8
7645585 1995
12
Fronto-metaphyseal dysplasia. Further delineation of the clinical syndrome. 8
7151303 1982
13
Frontometaphyseal dysplasia: autosomal dominant or X-linked? 8
7189217 1980
14
Frontometaphyseal dysplasia--evidence for X-linked inheritance. 8
7395904 1980
15
Frontometaphyseal dysplasia presenting as scoliosis. 8
649644 1978
16
Frontometaphyseal dysplasia: evidence for autosomal dominant inheritance. 8
998829 1976
17
Frontometaphyseal Dysplasia. Evidence for dominant inheritance. 8
1258835 1976
18
[Fronto-metaphyseal dysplasia]. 8
1094899 1975
19
Frontometaphyseal dysplasia. 8
5044403 1972
20
Fronto-metaphyseal dysplasia. A progressive disease of bone and connective tissue. 8
5026209 1972
21
Frontometaphyseal dysplasia. A new syndrome. 8
5807657 1969
22
[Effect of 6-month therapy with perindopril A on structural-functional state of arterial vascular bed in patients with chronic heart failure]. 38
24888193 2014
23
Transient endothelial dysfunction following flow-mediated dilation assessment. 38
21153030 2011

Variations for Frontometaphyseal Dysplasia 1

ClinVar genetic disease variations for Frontometaphyseal Dysplasia 1:

6 (show top 50) (show all 416)
# Gene Variation Type Significance SNP ID GRCh37 Pos GRCh38 Pos
1 FLNA NM_001110556.2(FLNA): c.3668C> T (p.Pro1223Leu) single nucleotide variant Pathogenic rs1060500716 X:153588495-153588495 X:154360127-154360127
2 FLNA NM_001110556.2(FLNA): c.5988_5989del (p.Cys1997fs) deletion Pathogenic rs1060500718 X:153581697-153581698 X:154353329-154353330
3 FLNA NM_001110556.2(FLNA): c.4840_4852del (p.Gly1614fs) deletion Pathogenic rs1557177086 X:153585895-153585907 X:154357527-154357539
4 FLNA NM_001110556.2(FLNA): c.999_1008dup (p.Asp337delinsArgGlnTer) duplication Pathogenic rs1557179357 X:153594987-153594996 X:154366619-154366628
5 FLNA NM_001110556.2(FLNA): c.3814del (p.Arg1272fs) deletion Pathogenic rs1557177636 X:153588265-153588265 X:154359897-154359897
6 FLNA NM_001110556.2(FLNA): c.3529G> T (p.Glu1177Ter) single nucleotide variant Pathogenic rs1557177738 X:153588634-153588634 X:154360266-154360266
7 FLNA NM_001110556.2(FLNA): c.3476A> C (p.Asp1159Ala) single nucleotide variant Pathogenic rs28935471 X:153588687-153588687 X:154360319-154360319
8 FLNA NM_001110556.2(FLNA): c.3865G> T (p.Gly1289Ter) single nucleotide variant Pathogenic X:153588214-153588214 X:154359846-154359846
9 FLNA NM_001110556.2(FLNA): c.2565+1G> A single nucleotide variant Pathogenic X:153590785-153590785 X:154362417-154362417
10 FLNA NM_001110556.2(FLNA): c.5643del (p.Asn1881fs) deletion Pathogenic X:153582326-153582326 X:154353958-154353958
11 FLNA NM_001110556.2(FLNA): c.7872_7873del (p.Glu2625fs) deletion Pathogenic X:153577288-153577289 X:154348923-154348924
12 FLNA NM_001110556.2(FLNA): c.5879dup (p.Met1960fs) duplication Pathogenic X:153581807-153581807 X:154353439-154353439
13 FLNA NM_001110556.2(FLNA): c.2452del (p.Ala818fs) deletion Pathogenic X:153590899-153590899 X:154362531-154362531
14 FLNA NM_001110556.2(FLNA): c.3296_3304delinsTCGG (p.Gly1099fs) indel Pathogenic X:153588859-153588867 X:154360491-154360499
15 FLNA NM_001110556.2(FLNA): c.676C> T (p.Arg226Ter) single nucleotide variant Pathogenic/Likely pathogenic X:153596053-153596053 X:154367685-154367685
16 FLNA NM_001110556.2(FLNA): c.3557C> T (p.Ser1186Leu) single nucleotide variant Pathogenic/Likely pathogenic rs137853312 X:153588606-153588606 X:154360238-154360238
17 FLNA NM_001110556.2(FLNA): c.4726G> A (p.Gly1576Arg) single nucleotide variant Pathogenic/Likely pathogenic rs797045044 X:153586596-153586596 X:154358228-154358228
18 FLNA NM_001110556.2(FLNA): c.5686+1G> C single nucleotide variant Likely pathogenic rs1557176315 X:153582282-153582282 X:154353914-154353914
19 FLNA NM_001110556.2(FLNA): c.4143-1G> T single nucleotide variant Likely pathogenic rs1557177485 X:153587775-153587775 X:154359407-154359407
20 FLNA NM_001110556.2(FLNA): c.4596_4598+5del deletion Likely pathogenic rs1557177279 X:153586808-153586815 X:154358440-154358447
21 FLNA NM_001110556.2(FLNA): c.4142+1G> A single nucleotide variant Likely pathogenic X:153587851-153587851 X:154359483-154359483
22 FLNA NM_001110556.2(FLNA): c.2023-4C> G single nucleotide variant Conflicting interpretations of pathogenicity rs368719012 X:153592744-153592744 X:154364376-154364376
23 FLNA NM_001110556.2(FLNA): c.3330G> A (p.Ala1110=) single nucleotide variant Conflicting interpretations of pathogenicity rs781917512 X:153588833-153588833 X:154360465-154360465
24 FLNA NM_001110556.2(FLNA): c.1450C> T (p.Arg484Trp) single nucleotide variant Conflicting interpretations of pathogenicity rs61730768 X:153593834-153593834 X:154365466-154365466
25 FLNA NM_001110556.2(FLNA): c.7092C> A (p.Ile2364=) single nucleotide variant Conflicting interpretations of pathogenicity rs782591917 X:153579341-153579341 X:154350973-154350973
26 FLNA NM_001110556.2(FLNA): c.4106C> T (p.Thr1369Ile) single nucleotide variant Conflicting interpretations of pathogenicity rs376774130 X:153587888-153587888 X:154359520-154359520
27 FLNA NM_001110556.2(FLNA): c.7779_7780insTTCGGGG (p.Val2594fs) insertion Conflicting interpretations of pathogenicity rs1557175195 X:153577381-153577382 X:154349013-154349014
28 FLNA NM_001110556.2(FLNA): c.1997C> T (p.Ala666Val) single nucleotide variant Conflicting interpretations of pathogenicity rs374295965 X:153592919-153592919 X:154364551-154364551
29 FLNA NM_001110556.2(FLNA): c.1900C> G (p.Arg634Gly) single nucleotide variant Conflicting interpretations of pathogenicity rs111516546 X:153593016-153593016 X:154364648-154364648
30 FLNA NM_001110556.2(FLNA): c.3036G> A (p.Ser1012=) single nucleotide variant Conflicting interpretations of pathogenicity rs373908435 X:153589847-153589847 X:154361479-154361479
31 FLNA NM_001110556.2(FLNA): c.2389G> A (p.Ala797Thr) single nucleotide variant Conflicting interpretations of pathogenicity rs201073998 X:153591044-153591044 X:154362676-154362676
32 FLNA NM_001110556.2(FLNA): c.7389G> A (p.Ser2463=) single nucleotide variant Conflicting interpretations of pathogenicity rs373103712 X:153578180-153578180 X:154349812-154349812
33 FLNA NM_001110556.2(FLNA): c.65A> G (p.Asp22Gly) single nucleotide variant Conflicting interpretations of pathogenicity rs782598729 X:153599549-153599549 X:154371181-154371181
34 FLNA NM_001110556.2(FLNA): c.4475-4C> T single nucleotide variant Conflicting interpretations of pathogenicity rs199652065 X:153586940-153586940 X:154358572-154358572
35 FLNA NM_001110556.2(FLNA): c.586C> T (p.Arg196Trp) single nucleotide variant Conflicting interpretations of pathogenicity rs137853317 X:153596246-153596246 X:154367878-154367878
36 FLNA NM_001110556.2(FLNA): c.1138G> A (p.Asp380Asn) single nucleotide variant Conflicting interpretations of pathogenicity X:153594766-153594766 X:154366398-154366398
37 FLNA NM_001110556.2(FLNA): c.1429+8C> T single nucleotide variant Conflicting interpretations of pathogenicity rs202181557 X:153594384-153594384 X:154366016-154366016
38 FLNA NM_001110556.2(FLNA): c.3379G> A (p.Val1127Met) single nucleotide variant Conflicting interpretations of pathogenicity rs398123617 X:153588784-153588784 X:154360416-154360416
39 FLNA NM_001110556.2(FLNA): c.4263C> T (p.Thr1421=) single nucleotide variant Conflicting interpretations of pathogenicity rs398123618 X:153587654-153587654 X:154359286-154359286
40 FLNA NM_001110556.2(FLNA): c.3147C> T (p.Gly1049=) single nucleotide variant Conflicting interpretations of pathogenicity rs398123615 X:153589736-153589736 X:154361368-154361368
41 FLNA NM_001110556.2(FLNA): c.1691+7C> A single nucleotide variant Conflicting interpretations of pathogenicity rs199565118 X:153593497-153593497 X:154365129-154365129
42 FLNA NM_001110556.2(FLNA): c.1239G> A (p.Thr413=) single nucleotide variant Conflicting interpretations of pathogenicity rs200278701 X:153594582-153594582 X:154366214-154366214
43 FLNA NM_001110556.2(FLNA): c.1579C> T (p.Arg527Cys) single nucleotide variant Conflicting interpretations of pathogenicity rs202029322 X:153593616-153593616 X:154365248-154365248
44 FLNA NM_001110556.2(FLNA): c.3045G> A (p.Ala1015=) single nucleotide variant Conflicting interpretations of pathogenicity rs370868704 X:153589838-153589838 X:154361470-154361470
45 FLNA NM_001110556.2(FLNA): c.2725G> A (p.Val909Ile) single nucleotide variant Conflicting interpretations of pathogenicity rs199911951 X:153590448-153590448 X:154362080-154362080
46 FLNA NM_001110556.2(FLNA): c.2178C> T (p.Asn726=) single nucleotide variant Conflicting interpretations of pathogenicity rs371501734 X:153592492-153592492 X:154364124-154364124
47 FLNA NM_001110556.2(FLNA): c.4451A> G (p.Gln1484Arg) single nucleotide variant Conflicting interpretations of pathogenicity rs200130356 X:153587375-153587375 X:154359007-154359007
48 FLNA NM_001110556.2(FLNA): c.4060G> A (p.Asp1354Asn) single nucleotide variant Conflicting interpretations of pathogenicity rs377390031 X:153587934-153587934 X:154359566-154359566
49 FLNA NM_001110556.2(FLNA): c.2023-6C> T single nucleotide variant Conflicting interpretations of pathogenicity rs372021340 X:153592746-153592746 X:154364378-154364378
50 FLNA NM_001110556.2(FLNA): c.2613C> T (p.Asp871=) single nucleotide variant Conflicting interpretations of pathogenicity rs188212919 X:153590653-153590653 X:154362285-154362285

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

74
# 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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