MCID: OTP006
MIFTS: 36

Otopalatodigital Syndrome, Type I

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

Aliases & Classifications for Otopalatodigital Syndrome, Type I

MalaCards integrated aliases for Otopalatodigital Syndrome, Type I:

Name: Otopalatodigital Syndrome, Type I 57 13 40
Oto-Palato-Digital Syndrome, Type I 25 29 6
Otopalatodigital Syndrome Type 1 53 25 59
Opd Syndrome 1 57 53 59
Taybi Syndrome 53 25 59
Opd1 57 53 75
Oto-Palato-Digital Syndrome Type 1 53 73
Opd I Syndrome 57 59
Faciopalatoosseous Syndrome 25
Otopalatodigital Syndrome 1 75
Cranioorodigital Syndrome 25
Opd Syndrome, Type 1 25
Opd Syndrome 53
Fpo 25

Characteristics:

Orphanet epidemiological data:

59
otopalatodigital syndrome type 1
Inheritance: X-linked dominant;

OMIM:

57
Inheritance:
x-linked dominant

Miscellaneous:
frontometaphyseal dysplasia (fmd, ) is an allelic disorder
melnick-needles syndrome (mns, ) is an allelic disorder
periventricular heterotopia is an allelic disorder
intermediate expression in females
complete manifestation in males
otopalatodigital syndrome type ii (opd2, ) is an allelic disorder with a more severe, frequently lethal phenotype


HPO:

32
otopalatodigital syndrome, type i:
Inheritance x-linked dominant inheritance


Classifications:



Summaries for Otopalatodigital Syndrome, Type I

NIH Rare Diseases : 53 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 90650Disease definitionOtopalatodigital syndrome type 1 (OPD1) is the mildest form of otopalatodigital syndrome spectrum disorder (see this term), and is characterized by a generalized skeletal dysplasia, mild intellectual disability, conductive hearing loss, and typical facial anomalies.EpidemiologyTo date, more than 100 cases have been described in the world literature.Clinical descriptionOPD1 is a congenital disorder characterized by generalized skeletal dysplasia which include camptodactyly, long spatulate fingers, short first digits (''tree frog'' hands and feet), pectus carinatum, mild campomelia, mild femoral bowing, limitation of joint movement (elbow extension, wrist abduction) and malformed auditory ossicles leading to conductive hearing loss in some individuals. Additional features include typical craniofacial anomalies (occipital prominence, frontal bossing with prominent supraorbital ridges, flat nasal bridge, hypertelorism, microstomia, dental abnormalities, and cleft palate (pugilistic face)). In affected females, a similar but usually milder spectrum of expressivity is observed.EtiologyOPD1 is caused by gain of function mutations in the geneFLNA (Xq28) that encodes filamin A. However the pathogenesis of OPD1 is still elusive. OPD1 is allelic with 4 other skeletal dysplasias (OPD2, Melnick-Needles syndrome (MNS), terminal osseous dysplasia - pigmentary defects (TOD) and frontometaphyseal dysplasia (FMD) (see these terms)).Genetic counselingOPD1 is inherited in an X-linked dominant manner. Male-to-male transmission has not been reported. The chance of transmitting the mutation in each pregnancy is 50%; males inheriting the mutation will be affected while females who inherit the mutation have a broad range of phenotypic expression.Visit the Orphanet disease page for more resources.

MalaCards based summary : Otopalatodigital Syndrome, Type I, also known as oto-palato-digital syndrome, type i, is related to rubinstein-taybi syndrome 2 and rubinstein-taybi syndrome 1. An important gene associated with Otopalatodigital Syndrome, Type I is FLNA (Filamin A). The drugs Valproic Acid and Anticonvulsants have been mentioned in the context of this disorder. Affiliated tissues include bone, kidney and heart, and related phenotypes are hypertelorism and prominent supraorbital ridges

Genetics Home Reference : 25 Otopalatodigital syndrome type 1 is a disorder primarily involving abnormalities in skeletal development. It is a member of a group of related conditions called otopalatodigital spectrum disorders, which also includes otopalatodigital syndrome type 2, frontometaphyseal dysplasia, 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).

OMIM : 57 Otopalatodigital syndrome-1 is 1 of 4 otopalatodigital syndromes caused by mutations in the FLNA gene. The disorders, which include frontometaphyseal dysplasia (FMD1; 305620), 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. FMD 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.' (311300)

UniProtKB/Swiss-Prot : 75 Otopalatodigital syndrome 1: X-linked dominant multiple congenital anomalies disease mainly characterized by a generalized skeletal dysplasia, mild mental retardation, hearing loss, cleft palate, and typical facial anomalies. OPD1 belongs to a group of X-linked skeletal dysplasias known as oto- palato-digital syndrome spectrum disorders that also include OPD2, Melnick-Needles syndrome (MNS), and frontometaphyseal dysplasia (FMD). Remodeling of the cytoskeleton is central to the modulation of cell shape and migration. FLNA is a widely expressed protein that regulates re-organization of the actin cytoskeleton by interacting with integrins, transmembrane receptor complexes and second messengers. Males with OPD1 have cleft palate, malformations of the ossicles causing deafness and milder bone and limb defects than those associated with OPD2. Obligate female carriers of mutations causing both OPD1 and OPD2 have variable (often milder) expression of a similar phenotypic spectrum.

Related Diseases for Otopalatodigital Syndrome, Type I

Diseases in the Otopalatodigital Spectrum Disorders family:

Otopalatodigital Syndrome, Type Ii Otopalatodigital Syndrome, Type I

Diseases related to Otopalatodigital Syndrome, Type I via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 11)
# Related Disease Score Top Affiliating Genes
1 rubinstein-taybi syndrome 2 12.4
2 rubinstein-taybi syndrome 1 12.4
3 chromosome 16p13.3 deletion syndrome, proximal 12.2
4 frontometaphyseal dysplasia 11.5
5 pilomatrixoma 11.2
6 otopalatodigital syndrome, type ii 11.1
7 frontometaphyseal dysplasia 1 11.0
8 melnick-needles syndrome 11.0
9 floating-harbor syndrome 10.9
10 coffin-lowry syndrome 10.9
11 type i 9.9

Graphical network of the top 20 diseases related to Otopalatodigital Syndrome, Type I:



Diseases related to Otopalatodigital Syndrome, Type I

Symptoms & Phenotypes for Otopalatodigital Syndrome, Type I

Symptoms via clinical synopsis from OMIM:

57
Head And Neck Eyes:
hypertelorism
downslanting palpebral fissures

Head And Neck Face:
frontal bossing
flat face

Head And Neck Head:
prominent supraorbital ridges
prominent occiput

Skin Nails Hair Nails:
nail dystrophy
short square fingernails

Skeletal Feet:
toe syndactyly
gap between first and second toes
short, broad halluces
'tree-frog' feet
anomalous fifth metatarsal
more
Skeletal Limbs:
limited elbow extension
radial head dislocation
limited knee flexion
mild, lateral femoral bowing

Skeletal Skull:
absent frontal sinuses
delayed closure of anterior fontanel
thick skull base
absent sphenoid sinuses
thick frontal bone
more
Head And Neck Nose:
small nose
broad nasal root

Skeletal Hands:
supernumerary carpal bones
short, broad distal phalanges, especially thumbs
short square nails
short third, fourth, fifth metacarpals
fusion of hamate and capitate

Chest Ribs Sternum Clavicles And Scapulae:
pectus excavatum

Skeletal Spine:
scoliosis
small pedicles

Head And Neck Mouth:
cleft palate
microstomia

Skeletal Pelvis:
coxa valga
hip dislocation
small iliac crests
flat acetabulum

Abdomen External Features:
omphalocele

Head And Neck Teeth:
selective tooth agenesis
impacted teeth

Head And Neck Ears:
conductive hearing loss

Neurologic Central Nervous System:
mild mental retardation

Growth Height:
short stature (<10th percentile for age)


Clinical features from OMIM:

311300

Human phenotypes related to Otopalatodigital Syndrome, Type I:

59 32 (show top 50) (show all 62)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 hypertelorism 59 32 hallmark (90%) Very frequent (99-80%) HP:0000316
2 prominent supraorbital ridges 59 32 hallmark (90%) Very frequent (99-80%) HP:0000336
3 hearing impairment 59 32 hallmark (90%) Very frequent (99-80%) HP:0000365
4 skeletal dysplasia 59 32 hallmark (90%) Very frequent (99-80%) HP:0002652
5 depressed nasal bridge 59 32 hallmark (90%) Very frequent (99-80%) HP:0005280
6 bowing of the long bones 59 32 frequent (33%) Frequent (79-30%) HP:0006487
7 wide nasal bridge 59 32 hallmark (90%) Very frequent (99-80%) HP:0000431
8 thickened calvaria 59 32 frequent (33%) Frequent (79-30%) HP:0002684
9 intellectual disability, mild 59 32 hallmark (90%) Very frequent (99-80%) HP:0001256
10 cleft palate 59 32 hallmark (90%) Very frequent (99-80%) HP:0000175
11 short palm 59 32 frequent (33%) Frequent (79-30%) HP:0004279
12 limitation of joint mobility 59 32 hallmark (90%) Very frequent (99-80%) HP:0001376
13 abnormality of the metacarpal bones 59 32 frequent (33%) Frequent (79-30%) HP:0001163
14 downslanted palpebral fissures 59 32 hallmark (90%) Very frequent (99-80%) HP:0000494
15 sandal gap 59 32 hallmark (90%) Very frequent (99-80%) HP:0001852
16 elbow dislocation 59 32 frequent (33%) Frequent (79-30%) HP:0003042
17 increased bone mineral density 59 32 frequent (33%) Frequent (79-30%) HP:0011001
18 short distal phalanx of finger 59 32 frequent (33%) Frequent (79-30%) HP:0009882
19 short hallux 59 32 hallmark (90%) Very frequent (99-80%) HP:0010109
20 synostosis of carpal bones 59 32 occasional (7.5%) Occasional (29-5%) HP:0005048
21 proximal placement of thumb 59 32 frequent (33%) Frequent (79-30%) HP:0009623
22 abnormal vertebral segmentation and fusion 59 32 occasional (7.5%) Occasional (29-5%) HP:0005640
23 hypoplastic frontal sinuses 59 32 frequent (33%) Frequent (79-30%) HP:0002738
24 oligodontia 59 32 hallmark (90%) Very frequent (99-80%) HP:0000677
25 short thumb 59 32 frequent (33%) Frequent (79-30%) HP:0009778
26 abnormality of the tarsal bones 59 32 occasional (7.5%) Occasional (29-5%) HP:0001850
27 anodontia 59 32 hallmark (90%) Very frequent (99-80%) HP:0000674
28 malar flattening 32 HP:0000272
29 pectus excavatum 32 HP:0000767
30 frontal bossing 32 HP:0002007
31 scoliosis 32 HP:0002650
32 short nose 32 HP:0003196
33 short stature 32 HP:0004322
34 nail dystrophy 32 HP:0008404
35 coxa valga 32 HP:0002673
36 prominent occiput 32 HP:0000269
37 flat face 32 HP:0012368
38 short 4th metacarpal 32 HP:0010044
39 short 5th metacarpal 32 HP:0010047
40 hip dislocation 32 HP:0002827
41 narrow mouth 32 HP:0000160
42 conductive hearing impairment 32 HP:0000405
43 nail dysplasia 32 HP:0002164
44 toe syndactyly 32 HP:0001770
45 capitate-hamate fusion 32 HP:0001241
46 omphalocele 32 HP:0001539
47 limited elbow extension 32 HP:0001377
48 dislocated radial head 32 HP:0003083
49 selective tooth agenesis 32 HP:0001592
50 delayed closure of the anterior fontanelle 32 HP:0001476

Drugs & Therapeutics for Otopalatodigital Syndrome, Type I

Drugs for Otopalatodigital Syndrome, Type I (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 9)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Valproic Acid Approved, Investigational Phase 2 99-66-1 3121
2 Anticonvulsants Phase 2
3 Antimanic Agents Phase 2
4 Central Nervous System Depressants Phase 2
5 GABA Agents Phase 2
6 Histone Deacetylase Inhibitors Phase 2
7 Neurotransmitter Agents Phase 2
8 Psychotropic Drugs Phase 2
9 Tranquilizing Agents Phase 2

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Rubinstein-Taybi Syndrome: Functional Imaging and Therapeutic Trial Completed NCT01619644 Phase 2 sodium valproate;Placebo

Search NIH Clinical Center for Otopalatodigital Syndrome, Type I

Genetic Tests for Otopalatodigital Syndrome, Type I

Genetic tests related to Otopalatodigital Syndrome, Type I:

# Genetic test Affiliating Genes
1 Oto-Palato-Digital Syndrome, Type I 29 FLNA

Anatomical Context for Otopalatodigital Syndrome, Type I

MalaCards organs/tissues related to Otopalatodigital Syndrome, Type I:

41
Bone, Kidney, Heart

Publications for Otopalatodigital Syndrome, Type I

Articles related to Otopalatodigital Syndrome, Type I:

# Title Authors Year
1
Refined mapping of the gene for otopalatodigital syndrome type I. ( 11836376 )
2002
2
Oto-palato-digital syndrome type I: further evidence for assignment of the locus to Xq28. ( 1757098 )
1991

Variations for Otopalatodigital Syndrome, Type I

UniProtKB/Swiss-Prot genetic disease variations for Otopalatodigital Syndrome, Type I:

75
# Symbol AA change Variation ID SNP ID
1 FLNA p.Pro207Leu VAR_015700 rs28935469
2 FLNA p.Leu172Phe VAR_015714
3 FLNA p.Arg196Trp VAR_015716 rs137853317
4 FLNA p.Asp203Tyr VAR_031308 rs137853314

ClinVar genetic disease variations for Otopalatodigital Syndrome, Type I:

6
(show all 32)
# Gene Variation Type Significance SNP ID Assembly Location
1 FLNA NM_001110556.1(FLNA): c.620C> T (p.Pro207Leu) single nucleotide variant Pathogenic rs28935469 GRCh37 Chromosome X, 153596212: 153596212
2 FLNA NM_001110556.1(FLNA): c.620C> T (p.Pro207Leu) single nucleotide variant Pathogenic rs28935469 GRCh38 Chromosome X, 154367844: 154367844
3 FLNA NM_001110556.1(FLNA): c.760G> A (p.Glu254Lys) single nucleotide variant Pathogenic rs28935470 GRCh37 Chromosome X, 153595873: 153595873
4 FLNA NM_001110556.1(FLNA): c.760G> A (p.Glu254Lys) single nucleotide variant Pathogenic rs28935470 GRCh38 Chromosome X, 154367505: 154367505
5 FLNA NM_001110556.1(FLNA): c.607G> T (p.Asp203Tyr) single nucleotide variant Pathogenic rs137853314 GRCh37 Chromosome X, 153596225: 153596225
6 FLNA NM_001110556.1(FLNA): c.607G> T (p.Asp203Tyr) single nucleotide variant Pathogenic rs137853314 GRCh38 Chromosome X, 154367857: 154367857
7 FLNA NM_001110556.1(FLNA): c.2761C> T (p.Arg921Ter) single nucleotide variant Pathogenic rs398123614 GRCh37 Chromosome X, 153590412: 153590412
8 FLNA NM_001110556.1(FLNA): c.2761C> T (p.Arg921Ter) single nucleotide variant Pathogenic rs398123614 GRCh38 Chromosome X, 154362044: 154362044
9 FLNA NM_001110556.1(FLNA): c.3153dupC (p.Val1052Argfs) duplication Pathogenic rs398123616 GRCh37 Chromosome X, 153589730: 153589730
10 FLNA NM_001110556.1(FLNA): c.3153dupC (p.Val1052Argfs) duplication Pathogenic rs398123616 GRCh38 Chromosome X, 154361362: 154361362
11 FLNA NM_001110556.1(FLNA): c.42delC (p.Ala15Argfs) deletion Pathogenic rs398123619 GRCh37 Chromosome X, 153599572: 153599572
12 FLNA NM_001110556.1(FLNA): c.42delC (p.Ala15Argfs) deletion Pathogenic rs398123619 GRCh38 Chromosome X, 154371204: 154371204
13 FLNA NM_001110556.1(FLNA): c.4447_4448insAT (p.Leu1483Tyrfs) insertion Pathogenic rs398123620 GRCh37 Chromosome X, 153587378: 153587379
14 FLNA NM_001110556.1(FLNA): c.4447_4448insAT (p.Leu1483Tyrfs) insertion Pathogenic rs398123620 GRCh38 Chromosome X, 154359010: 154359011
15 FLNA NM_001110556.1(FLNA): c.4543C> T (p.Arg1515Ter) single nucleotide variant Pathogenic rs186214592 GRCh37 Chromosome X, 153586868: 153586868
16 FLNA NM_001110556.1(FLNA): c.4543C> T (p.Arg1515Ter) single nucleotide variant Pathogenic rs186214592 GRCh38 Chromosome X, 154358500: 154358500
17 FLNA NM_001110556.1(FLNA): c.5132_5133delTCinsAA (p.Phe1711Ter) indel Pathogenic rs398123621 GRCh37 Chromosome X, 153583277: 153583278
18 FLNA NM_001110556.1(FLNA): c.5132_5133delTCinsAA (p.Phe1711Ter) indel Pathogenic rs398123621 GRCh38 Chromosome X, 154354909: 154354910
19 FLNA NM_001456.3(FLNA): c.7527_7528+6delAGGTGAGC deletion Pathogenic rs398123623 GRCh37 Chromosome X, 153578011: 153578018
20 FLNA NM_001456.3(FLNA): c.7527_7528+6delAGGTGAGC deletion Pathogenic rs398123623 GRCh38 Chromosome X, 154349643: 154349650
21 FLNA NM_001110556.1(FLNA): c.7153C> T (p.Gln2385Ter) single nucleotide variant Pathogenic rs727503931 GRCh37 Chromosome X, 153579280: 153579280
22 FLNA NM_001110556.1(FLNA): c.7153C> T (p.Gln2385Ter) single nucleotide variant Pathogenic rs727503931 GRCh38 Chromosome X, 154350912: 154350912
23 FLNA NM_001110556.1(FLNA): c.7757-1G> C single nucleotide variant Pathogenic rs797044496 GRCh37 Chromosome X, 153577405: 153577405
24 FLNA NM_001110556.1(FLNA): c.7757-1G> C single nucleotide variant Pathogenic rs797044496 GRCh38 Chromosome X, 154349037: 154349037
25 FLNA NM_001456.3(FLNA): c.4777_4778dupAA (p.Thr1594Argfs) duplication Pathogenic rs786200973 GRCh37 Chromosome X, 153585969: 153585970
26 FLNA NM_001456.3(FLNA): c.4777_4778dupAA (p.Thr1594Argfs) duplication Pathogenic rs786200973 GRCh38 Chromosome X, 154357601: 154357602
27 FLNA NM_001110556.1(FLNA): c.5854delG (p.Val1952Serfs) deletion Pathogenic rs797044724 GRCh37 Chromosome X, 153581928: 153581928
28 FLNA NM_001110556.1(FLNA): c.5854delG (p.Val1952Serfs) deletion Pathogenic rs797044724 GRCh38 Chromosome X, 154353560: 154353560
29 FLNA NM_001110556.1(FLNA): c.1571G> A (p.Gly524Glu) single nucleotide variant not provided GRCh37 Chromosome X, 153593624: 153593624
30 FLNA NM_001110556.1(FLNA): c.1571G> A (p.Gly524Glu) single nucleotide variant not provided GRCh38 Chromosome X, 154365256: 154365256
31 FLNA NM_001456.3(FLNA): c.2309A> G (p.Asn770Ser) single nucleotide variant Likely benign GRCh37 Chromosome X, 153591124: 153591124
32 FLNA NM_001456.3(FLNA): c.2309A> G (p.Asn770Ser) single nucleotide variant Likely benign GRCh38 Chromosome X, 154362756: 154362756

Expression for Otopalatodigital Syndrome, Type I

Search GEO for disease gene expression data for Otopalatodigital Syndrome, Type I.

Pathways for Otopalatodigital Syndrome, Type I

GO Terms for Otopalatodigital Syndrome, Type I

Sources for Otopalatodigital Syndrome, Type I

3 CDC
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71 TGDB
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74 UMLS via Orphanet
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