TOD
MCID: TRM011
MIFTS: 38

Terminal Osseous Dysplasia (TOD)

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

Aliases & Classifications for Terminal Osseous Dysplasia

MalaCards integrated aliases for Terminal Osseous Dysplasia:

Name: Terminal Osseous Dysplasia 57 12 43 73 36 29 13 6 39
Terminal Osseous Dysplasia and Pigmentary Defects 57 43 73 71
Todpd 57 12 43 73
Terminal Osseous Dysplasia-Pigmentary Defects Syndrome 12 43 58
Odpf Syndrome 57 12 73
Odpd 57 12 73
Tod 57 12 73
Digital Osseous Dysplasia with Facial Pigmentary Defects and Multiple Frenula 12 73
Odpf 57 73
Osseous Dysplasia, Digital, with Facial Pigmentary Defects and Multiple Frenula; Odpf 57
Osseous Dysplasia, Digital, with Facial Pigmentary Defects and Multiple Frenula 57
Terminal Osseous Dysplasia and Pigmentary Defect Syndrome 43
Terminal Osseous Dysplasia and Pigmentary Defects; Todpd 57
Terminal Osseous Dysplasia with Pigmentary Defects 43
Osseous Dysplasia and Pigmentary Defects 73
Digitocutaneous Dysplasia 43
Dcd 43

Characteristics:

Orphanet epidemiological data:

58
terminal osseous dysplasia-pigmentary defects syndrome
Inheritance: X-linked dominant; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal; Age of death: normal life expectancy;

OMIM®:

57 (Updated 05-Mar-2021)
Inheritance:
x-linked dominant


HPO:

31
terminal osseous dysplasia:
Inheritance x-linked dominant inheritance


Classifications:

Orphanet: 58  
Rare bone diseases
Rare skin diseases
Developmental anomalies during embryogenesis


External Ids:

Disease Ontology 12 DOID:0112149
OMIM® 57 300244
KEGG 36 H02229
MeSH 44 D001848
ICD10 via Orphanet 33 Q87.2
UMLS via Orphanet 72 C1846129
Orphanet 58 ORPHA88630
MedGen 41 C1846129
UMLS 71 C1846129

Summaries for Terminal Osseous Dysplasia

MedlinePlus Genetics : 43 Terminal osseous dysplasia is a disorder primarily involving skeletal abnormalities and certain skin changes. 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, frontometaphyseal dysplasia, and Melnick-Needles syndrome. In general, these disorders involve hearing loss caused by malformations in tiny bones in the ears (ossicles), problems in the development of the roof of the mouth (palate), and skeletal abnormalities involving the fingers or toes (digits), although not every condition in the spectrum has all of these features.Terminal osseous dysplasia occurs only in females; males with the condition do not survive to birth. The skeletal abnormalities in people with this condition typically include permanently bent fingers and toes (camptodactyly) and underdevelopment (hypoplasia), shortening, or fusion of the bones in the wrists and hands. The outer layer of bone (cortex) in other parts of the skeleton may be abnormal, and some affected individuals have bowed arms or legs or are shorter than their peers.Skin abnormalities are also common in terminal osseous dysplasia. Many individuals with the condition have dark patches of skin on their face, often near the temples. In addition, affected infants commonly develop noncancerous (benign) tumors called fibromas on their fingers or toes. The tumors may reappear after being removed, but they tend to go away and stop reoccurring in childhood.Other signs and symptoms can occur in people with terminal osseous dysplasia, including extra oral frenulae, which are the thin pieces of tissue in the mouth that connect the inside of the lips to the gums; widely spaced eyes; and hair loss. Some people with this condition have an abnormality in the muscular wall (septum) that separates the right and left sides of the heart (cardiac septal defect).

MalaCards based summary : Terminal Osseous Dysplasia, also known as terminal osseous dysplasia and pigmentary defects, is related to otopalatodigital syndrome, type ii and frontometaphyseal dysplasia. An important gene associated with Terminal Osseous Dysplasia is FLNA (Filamin A). Affiliated tissues include cortex, bone and skin, and related phenotypes are mesomelic arm shortening and mesomelic leg shortening

Disease Ontology : 12 A syndrome characterized by skeletal dysplasia of the limbs, pigmentary defects of the skin, and recurrent digital fibroma during infancy that has material basis in heterozygous mutation in FLNA on chromosome Xq28.

OMIM® : 57 Terminal osseous dysplasia is an X-linked dominant male-lethal disease characterized by skeletal dysplasia of the limbs, pigmentary defects of the skin, and recurrent digital fibroma during infancy (Sun et al., 2010). (300244) (Updated 05-Mar-2021)

KEGG : 36 Terminal osseous dysplasia (TOD) is an X-linked dominant male-lethal disease characterized by skeletal dysplasia of the limbs, pigmentary defects of the skin, and recurrent digital fibroma with onset in female infancy. TOD is caused by a mutation in the FLNA gene.

UniProtKB/Swiss-Prot : 73 Terminal osseous dysplasia: A rare X-linked dominant male-lethal disease characterized by skeletal dysplasia of the limbs, pigmentary defects of the skin and recurrent digital fibroma during infancy. A significant phenotypic variability is observed in affected females.

Wikipedia : 74 Terminal osseous dysplasia with pigmentary defects is a cutaneous condition characterized by... more...

Related Diseases for Terminal Osseous Dysplasia

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

(show top 50) (show all 75)
# Related Disease Score Top Affiliating Genes
1 otopalatodigital syndrome, type ii 32.1 LOC107988032 FLNA
2 frontometaphyseal dysplasia 31.9 LOC107988032 FLNA
3 melnick-needles syndrome 31.7 LOC107988032 FLNA
4 otopalatodigital syndrome, type i 11.3
5 developmental coordination disorder 11.3
6 netherton syndrome 11.1
7 root caries 11.1
8 skin disease 11.1
9 tinea pedis 10.9
10 angiomyoma 10.9
11 developmental dyspraxia 10.8
12 cardiac arrest 10.4
13 fibromatosis 10.3
14 attention deficit-hyperactivity disorder 10.3
15 ischemia 10.2
16 brachydactyly 10.2
17 agenesis of corpus callosum, cardiac, ocular, and genital syndrome 10.2
18 intestinal pseudoobstruction, neuronal, chronic idiopathic, x-linked 10.1 LOC107988032 FLNA
19 cerebral palsy 10.1
20 flna-related periventricular nodular heterotopia 10.1 LOC107988032 FLNA
21 periventricular nodular heterotopia 10.1 LOC107988032 FLNA
22 fg syndrome 2 10.1 LOC107988032 FLNA
23 periventricular nodular heterotopia 1 10.1 LOC107988032 FLNA
24 hypertelorism 10.1
25 fibroma 10.1
26 x-linked otopalatodigital spectrum disorders 10.1
27 infantile digital fibromatosis 10.1
28 frontometaphyseal dysplasia 1 10.1 LOC107988032 FLNA
29 ventricular fibrillation, paroxysmal familial, 1 10.1
30 agnosia 10.1
31 cardiac valvular dysplasia, x-linked 10.1 LOC107988032 FLNA
32 oto-palatal-digital syndrome 10.0 LOC107988032 FLNA
33 blood group, i system 10.0 LOC107988032 FLNA
34 global developmental delay, absent or hypoplastic corpus callosum, and dysmorphic facies 10.0
35 legionellosis 10.0
36 hepatitis a 10.0
37 neisseria meningitidis infection 10.0
38 isolated growth hormone deficiency, type ia 10.0
39 dwarfism 10.0
40 congenital heart defects, hamartomas of tongue, and polysyndactyly 9.9
41 nodular neuronal heterotopia 9.9 LOC107988032 FLNA
42 cholangiocarcinoma 9.9
43 helix syndrome 9.9
44 anhidrosis 9.9
45 vascular disease 9.9
46 ectodermal dysplasia 9.9
47 intrahepatic cholangiocarcinoma 9.9
48 hypopituitarism 9.9
49 48,xyyy 9.9
50 congenital hemidysplasia with ichthyosiform erythroderma and limb defects 9.8

Graphical network of the top 20 diseases related to Terminal Osseous Dysplasia:



Diseases related to Terminal Osseous Dysplasia

Symptoms & Phenotypes for Terminal Osseous Dysplasia

Human phenotypes related to Terminal Osseous Dysplasia:

31 (show all 24)
# Description HPO Frequency HPO Source Accession
1 mesomelic arm shortening 31 occasional (7.5%) HP:0005011
2 mesomelic leg shortening 31 occasional (7.5%) HP:0004987
3 cleft palate 31 very rare (1%) HP:0000175
4 ptosis 31 HP:0000508
5 hypertelorism 31 HP:0000316
6 low-set ears 31 HP:0000369
7 epicanthus 31 HP:0000286
8 short toe 31 HP:0001831
9 multiple joint contractures 31 HP:0002828
10 fibroma 31 HP:0010614
11 brachydactyly 31 HP:0001156
12 iris coloboma 31 HP:0000612
13 malar flattening 31 HP:0000272
14 telecanthus 31 HP:0000506
15 camptodactyly of finger 31 HP:0100490
16 toe clinodactyly 31 HP:0001863
17 abnormality of skin pigmentation 31 HP:0001000
18 abnormal oral frenulum morphology 31 HP:0000190
19 depressed nasal tip 31 HP:0000437
20 camptodactyly of toe 31 HP:0001836
21 syndactyly 31 HP:0001159
22 localized skin lesion 31 HP:0011355
23 abnormal hand bone ossification 31 HP:0010660
24 abnormal foot bone ossification 31 HP:0010675

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Mar-2021)
Head And Neck Eyes:
hypertelorism
telecanthus
epicanthic folds
coloboma of iris
upslanting palpebral fissure

Head And Neck Nose:
depressed nasal tip
flat nasal tip

Head And Neck Ears:
preauricular pits (rare)
preauricular tags (rare)

Skeletal Feet:
metatarsal disorganization

Skeletal Hands:
brachydactyly
camptodactyly
clinodactyly
syndactyly
metacarpal disorganization

Head And Neck Mouth:
thick lips
cleft palate (rare)
prominent lips
multiple frenula

Skeletal Limbs:
long bone anomalies
articular abnormalities

Skin Nails Hair Skin:
pigmentary skin anomalies (on face and scalp)
digital fibromas

Clinical features from OMIM®:

300244 (Updated 05-Mar-2021)

Drugs & Therapeutics for Terminal Osseous Dysplasia

Search Clinical Trials , NIH Clinical Center for Terminal Osseous Dysplasia

Genetic Tests for Terminal Osseous Dysplasia

Genetic tests related to Terminal Osseous Dysplasia:

# Genetic test Affiliating Genes
1 Terminal Osseous Dysplasia 29 FLNA

Anatomical Context for Terminal Osseous Dysplasia

MalaCards organs/tissues related to Terminal Osseous Dysplasia:

40
Cortex, Bone, Skin

Publications for Terminal Osseous Dysplasia

Articles related to Terminal Osseous Dysplasia:

(show all 20)
# Title Authors PMID Year
1
Terminal osseous dysplasia with pigmentary defects (TODPD) in a Turkish girl with new skin findings. 61 6 57
30561107 2019
2
Terminal osseous dysplasia is caused by a single recurrent mutation in the FLNA gene. 57 61 6
20598277 2010
3
Terminal osseous dysplasia with pigmentary defects: clinical description of a new family. 61 57 6
17152064 2007
4
Noninclusion-body infantile digital fibromatosis: a lesion heralding terminal osseous dysplasia and pigmentary defects syndrome. 6 57 61
15864382 2005
5
Recurrent digital fibroma, focal dermal hypoplasia, and limb malformations. 6 57
10982965 2000
6
A syndrome of digital fibromas, facial pigmentary dysplasia, and metacarpal and metatarsal disorganization. 57 6
9800904 1998
7
Terminal osseous dysplasia with pigmentary defects (TODPD): Follow-up of the first reported family, characterization of the radiological phenotype, and refinement of the linkage region. 61 57
20583181 2010
8
Terminal osseous dysplasia and pigmentary defects in a Brazilian girl. 61 57
18792982 2008
9
Terminal osseous dysplasia and pigmentary defects: clinical characterization of a novel male lethal X-linked syndrome. 57 61
10982966 2000
10
Terminal osseous dysplasia with pigmentary defects maps to human chromosome Xq27.3-xqter. 57 61
10739772 2000
11
Recurring digital fibroma of infancy. 57
4452723 1974
12
Terminal osseous dysplasia with pigmentary defects in a Chinese girl with the FLNA mutation: A case report and published work review. 61
31919883 2020
13
Terminal osseous dysplasia presenting with intracytoplasmic inclusion bodies in digital fibromas. 61
30168171 2018
14
Terminal osseous dysplasia with pigmentary defects; Case and brief review of filamin A-related disorders. 61
26061098 2016
15
Anetoderma in a patient with terminal osseous dysplasia with pigmentary defects. 61
26059211 2015
16
Terminal osseous dysplasia with pigmentary defects (TODPD) due to a recurrent filamin A (FLNA) mutation. 61
25614868 2014
17
Focal dermal hypoplasia with subependymal heterotopia and hypoplastic corpus callosum. 61
17159518 2007
18
X-Linked Otopalatodigital Spectrum Disorders 61
20301567 2005
19
New syndrome: focal dermal hypoplasia, morning glory anomaly, and polymicrogyria. 61
14699622 2004
20
Clinical manifestations of terminal osseous dysplasia and pigmentary defects in a young girl. 61
12738953 2003

Variations for Terminal Osseous Dysplasia

ClinVar genetic disease variations for Terminal Osseous Dysplasia:

6 (show all 16)
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 FLNA NM_001110556.2(FLNA):c.5217G>A (p.Thr1739=) SNV Pathogenic 11775 rs387907371 X:153583193-153583193 X:154354825-154354825
2 FLNA NM_001110556.2(FLNA):c.546G>C (p.Gln182His) SNV Uncertain significance 548502 rs1557179648 X:153596286-153596286 X:154367918-154367918
3 LOC107988032 NM_001110556.2(FLNA):c.7628G>A (p.Cys2543Tyr) SNV Uncertain significance 392335 X:153577858-153577858 X:154349490-154349490
4 FLNA NM_001110556.2(FLNA):c.6863G>A (p.Arg2288His) SNV Uncertain significance 465015 rs782275601 X:153580296-153580296 X:154351928-154351928
5 FLNA NM_001110556.2(FLNA):c.6725G>A (p.Arg2242Gln) SNV Uncertain significance 435203 rs781984274 X:153580593-153580593 X:154352225-154352225
6 FLNA NM_001110556.2(FLNA):c.6719A>G (p.Lys2240Arg) SNV Uncertain significance 211024 rs797045581 X:153580599-153580599 X:154352231-154352231
7 FLNA NM_001110556.2(FLNA):c.6376C>T (p.Pro2126Ser) SNV Uncertain significance 533577 rs782400832 X:153581143-153581143 X:154352775-154352775
8 FLNA NM_001110556.2(FLNA):c.2254G>A (p.Val752Ile) SNV Uncertain significance 432226 rs1297013254 X:153592416-153592416 X:154364048-154364048
9 FLNA NM_001110556.2(FLNA):c.901C>T (p.Arg301Trp) SNV Uncertain significance 198133 rs192609440 X:153595186-153595186 X:154366818-154366818
10 FLNA NM_001110556.2(FLNA):c.569G>A (p.Arg190Gln) SNV Uncertain significance 213491 rs782447567 X:153596263-153596263 X:154367895-154367895
11 FLNA NM_001110556.2(FLNA):c.4314C>G (p.Phe1438Leu) SNV Uncertain significance 625948 rs1557177412 X:153587512-153587512 X:154359144-154359144
12 FLNA NM_001110556.2(FLNA):c.2974A>G (p.Thr992Ala) SNV Uncertain significance 588552 rs782445995 X:153589909-153589909 X:154361541-154361541
13 FLNA NM_001110556.2(FLNA):c.2364G>A (p.Glu788=) SNV Uncertain significance 625949 rs1448428046 X:153591069-153591069 X:154362701-154362701
14 FLNA NM_001110556.2(FLNA):c.1204A>G (p.Thr402Ala) SNV Uncertain significance 625950 rs1569551838 X:153594700-153594700 X:154366332-154366332
15 FLNA NM_001110556.2(FLNA):c.3323G>A (p.Cys1108Tyr) SNV Uncertain significance 93756 rs371677498 X:153588840-153588840 X:154360472-154360472
16 FLNA NM_001110556.2(FLNA):c.494A>G (p.Lys165Arg) SNV Uncertain significance 625951 rs1569551874 X:153596338-153596338 X:154367970-154367970

Expression for Terminal Osseous Dysplasia

Search GEO for disease gene expression data for Terminal Osseous Dysplasia.

Pathways for Terminal Osseous Dysplasia

GO Terms for Terminal Osseous Dysplasia

Cellular components related to Terminal Osseous Dysplasia according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cellular_component GO:0005575 8.8 MAGEA9B MAGEA9 MAGEA6

Biological processes related to Terminal Osseous Dysplasia according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 biological_process GO:0008150 8.8 MAGEA9B MAGEA9 MAGEA6

Molecular functions related to Terminal Osseous Dysplasia according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 molecular_function GO:0003674 8.8 MAGEA9B MAGEA9 MAGEA6

Sources for Terminal Osseous Dysplasia

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Mar-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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