TDO
MCID: TRC118
MIFTS: 43

Trichodentoosseous Syndrome (TDO)

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

Aliases & Classifications for Trichodentoosseous Syndrome

MalaCards integrated aliases for Trichodentoosseous Syndrome:

Name: Trichodentoosseous Syndrome 56 73
Tricho-Dento-Osseous Syndrome 12 74 52 58 36 29 6 43 39 71
Tdo Syndrome 56 12 52 58 73 54
Trichodontoosseous Syndrome 56 12 13 15
Tdo 56 73
Enamel Hypoplasia and Hypocalcification with Associated Strikingly Curly Hair 52

Characteristics:

Orphanet epidemiological data:

58
tricho-dento-osseous syndrome
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Worldwide); Age of onset: Childhood; Age of death: any age;

OMIM:

56
Inheritance:
autosomal dominant

Miscellaneous:
hair tends to straighten by 2nd-3rd decade


HPO:

31
trichodentoosseous syndrome:
Inheritance autosomal dominant inheritance


Classifications:

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


External Ids:

Disease Ontology 12 DOID:0111565
OMIM 56 190320
KEGG 36 H00487
SNOMED-CT 67 38993008
MESH via Orphanet 44 C536549
ICD10 via Orphanet 33 Q82.4
UMLS via Orphanet 72 C0265333
Orphanet 58 ORPHA3352
MedGen 41 C0265333
UMLS 71 C0265333

Summaries for Trichodentoosseous Syndrome

NIH Rare Diseases : 52 The following summary is from Orphanet , a European reference portal for information on rare diseases and orphan drugs. Orpha Number: 3352 Definition Tricho-dento-osseous dysplasia (TDO) belongs to the ectodermal dysplasias and is characterised by curly/kinky hair at birth, enamel hypoplasia with discolouration and molar taurodontism, increased overall bone mineral density (BMD) and increased thickness of the cortical bones of the skull. Epidemiology The prevalence is unknown but the disease has been described in at least 8 families with over 30 affected members in some large kindreds. Clinical description The disease shows significant inter and intrafamilial clinical variation, with enamel hypoplasia and taurodontism being the most consistent features, however, the extent of the enamel defects may also vary between affected family members. The hair and bone manifestations are more variable and age dependent. Curly/kinky hair is present at birth in around 80% of patients, but around half of these patients loose the hair phenotype by adolescence. The BMD measurements show increasing variability with age, particularly in the radius and ulna. In addition, spinal BMD shows an increase with age. Other reported features include flat/brittle fingernails, increased susceptibility for caries and abscesses, delayed dental eruption, tubular sclerosis of the long bones, dolichocephaly (as a result of craniosynostosis ), and an absence of mastoid pneumatisation, the frontal sinus and calvarial diploe. Etiology The syndrome is caused by mutations in the distal-less homeobox gene (DLX3 ), located on the long arm of chromosome 17 (17q21.3-q22). Diagnostic methods Diagnosis can be made by clinical and radiological examination and confirmed by detection of DLX3 mutations. Differential diagnosis The differential diagnosis should include amelogenesis imperfecta, hypomaturation-hypoplastic type, with taurodontism (AIHHT), oculodentoosseous dysplasia (see this term) and the autosomal dominant form of osteopetrosis (see this term). Genetic counseling The disease is transmitted as a highly penetrant autosomal dominant trait . Management and treatment Treatment is symptomatic and patients require frequent dental follow-up. Prognosis The prognosis is good and there appearsto be no predisposition for developing fractures. Visit the Orphanet disease page for more resources.

MalaCards based summary : Trichodentoosseous Syndrome, also known as tricho-dento-osseous syndrome, is related to taurodontism and hypoplastic amelogenesis imperfecta. An important gene associated with Trichodentoosseous Syndrome is DLX3 (Distal-Less Homeobox 3). Affiliated tissues include bone and skin, and related phenotypes are widely spaced teeth and frontal bossing

Disease Ontology : 12 A syndrome characterized by curly kinky hair at birth, enamel hypoplasia, taurodontism, thickening of cortical bones and variable expression of craniofacial morphology that has material basis in heterozygous mutation in DLX3 on chromosome 17q21.33.

OMIM : 56 Trichodentoosseous syndrome is an autosomal dominant disorder with complete penetrance characterized by abnormalities involving hair, teeth, and bone (summary by Nguyen et al., 2013). (190320)

KEGG : 36 Tricho-dento-osseous syndrome (TDO) is a dysplasia with an autosomal dominant mode of inheritance. Mutation in DLX3 leads to the defects in hair, teeth, and bone.

UniProtKB/Swiss-Prot : 73 Trichodentoosseous syndrome: An autosomal dominant disease characterized by curly kinky hair at birth, enamel hypoplasia, taurodontism, thickening of cortical bones and variable expression of craniofacial morphology.

Wikipedia : 74 Tricho-dento-osseous syndrome (TDO) is a rare, systemic, autosomal dominant genetic disorder that causes... more...

Related Diseases for Trichodentoosseous Syndrome

Diseases related to Trichodentoosseous Syndrome via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 55)
# Related Disease Score Top Affiliating Genes
1 taurodontism 30.4 DSPP DLX3
2 hypoplastic amelogenesis imperfecta 29.8 FAM20A ENAM DLX3 AMBN
3 dentin dysplasia 27.8 MSX2 MMP25 MMP20 ENAM DSPP AMBN
4 amelogenesis imperfecta 26.0 WDR72 ODAPH MSX2 MMP25 MMP20 FAM83H
5 ectodermal dysplasia 10.7
6 brittle bone disorder 10.5
7 alacrima, achalasia, and mental retardation syndrome 10.5
8 endosteal hyperostosis, autosomal dominant 10.4
9 melorheostosis, isolated 10.4
10 melorheostosis 10.4
11 odontoma 10.4
12 alpha/beta t-cell lymphopenia with gamma/delta t-cell expansion, severe cytomegalovirus infection, and autoimmunity 10.2
13 glioma 10.2
14 glial tumor 10.2
15 amelogenesis imperfecta, type ic 10.2 MMP20 ENAM
16 amelogenesis imperfecta, type iv 10.1
17 autoimmune disease 10.1
18 hepatocellular carcinoma 10.1
19 huntington disease 10.1
20 diffuse large b-cell lymphoma 10.1
21 mental depression 10.1
22 severe acute respiratory syndrome 10.1
23 glioblastoma multiforme 10.1
24 b-cell lymphoma 10.1
25 allergic encephalomyelitis 10.1
26 depression 10.1
27 amelogenesis imperfecta, hypoplastic/hypomaturation, x-linked 2 10.1 ENAM AMBN
28 papillary craniopharyngioma 10.1 MMP20 ENAM
29 enamel caries 10.1 ENAM AMBN
30 tooth ankylosis 10.0 ODAPH AMBN
31 junctional epidermolysis bullosa 10.0 WDR72 ODAPH ENAM
32 amelogenesis imperfecta, hypomaturation type, iia2 10.0 WDR72 ODAPH MMP20
33 amelogenesis imperfecta hypomaturation type 10.0 WDR72 ODAPH MMP20
34 amelogenesis imperfecta, type ib 9.9 MMP20 ENAM AMBN
35 dental abscess 9.9 DSPP DLX3
36 syngnathia 9.8 MSX2 DLX2
37 dentin caries 9.8 MMP20 DSPP
38 tooth erosion 9.8 ENAM DSPP
39 gingival disease 9.7 FAM20A AMBN
40 pulp degeneration 9.7 DSPP AMBN
41 hyaline fibromatosis syndrome 9.6 MSX2 DLX3
42 cleft palate, isolated 9.6 MSX2 DLX5 DLX4 DLX3
43 gingival recession 9.5 DSPP AMBN
44 dental caries 9.5 ENAM DSPP AMBN
45 tooth resorption 9.5 DSPP AMBN
46 amelogenesis imperfecta, type iiia 9.4 WDR72 MMP20 FAM83H ENAM AMBN
47 orofacial cleft 9.4 MSX2 DLX5 DLX4 DLX3 DLX2
48 suppurative periapical periodontitis 9.3 FAM20A DSPP DLX3 AMBN
49 odontochondrodysplasia 9.3 MSX2 DSPP DLX5 DLX3
50 hypercementosis 9.0 MMP20 FAM83H ENAM DSPP AMBN

Graphical network of the top 20 diseases related to Trichodentoosseous Syndrome:



Diseases related to Trichodentoosseous Syndrome

Symptoms & Phenotypes for Trichodentoosseous Syndrome

Human phenotypes related to Trichodentoosseous Syndrome:

58 31 (show all 17)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 widely spaced teeth 58 31 frequent (33%) Frequent (79-30%) HP:0000687
2 frontal bossing 58 31 frequent (33%) Frequent (79-30%) HP:0002007
3 microdontia 58 31 frequent (33%) Frequent (79-30%) HP:0000691
4 dolichocephaly 58 31 frequent (33%) Frequent (79-30%) HP:0000268
5 taurodontia 58 31 frequent (33%) Frequent (79-30%) HP:0000679
6 increased bone mineral density 58 31 frequent (33%) Frequent (79-30%) HP:0011001
7 abnormal hair quantity 58 31 frequent (33%) Frequent (79-30%) HP:0011362
8 fragile nails 58 31 frequent (33%) Frequent (79-30%) HP:0001808
9 abnormality of the mastoid 58 31 frequent (33%) Frequent (79-30%) HP:0000264
10 hypomineralization of enamel 58 31 frequent (33%) Frequent (79-30%) HP:0006285
11 dental enamel pits 58 31 frequent (33%) Frequent (79-30%) HP:0009722
12 obliteration of the calvarial diploe 58 31 frequent (33%) Frequent (79-30%) HP:0030312
13 periapical tooth abscess 58 31 frequent (33%) Frequent (79-30%) HP:0030758
14 finger clinodactyly 58 31 occasional (7.5%) Occasional (29-5%) HP:0040019
15 agenesis of incisor 58 31 occasional (7.5%) Occasional (29-5%) HP:0006485
16 abnormality of the nail 58 Frequent (79-30%)
17 abnormal hair morphology 31 HP:0001595

Symptoms via clinical synopsis from OMIM:

56
Head And Neck Face:
frontal bossing

Head And Neck Teeth:
taurodontism
thin enamel
small, widely spaced teeth
teeth pits
periapical abscesses

Skeletal:
increased bone density, mild-moderate (skull, spine, long bones)

Skin Nails Hair Hair:
kinky hair

Head And Neck Head:
dolichocephaly

Skin Nails Hair Nails:
brittle nails

Skeletal Skull:
obliteration of calvarial diploe
poorly pneumatized mastoids

Clinical features from OMIM:

190320

MGI Mouse Phenotypes related to Trichodentoosseous Syndrome:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 craniofacial MP:0005382 9.85 AMBN CNNM4 DLX2 DLX5 ENAM FAM20A
2 growth/size/body region MP:0005378 9.7 AMBN CNNM4 DLX2 DLX3 DLX5 ENAM
3 skeleton MP:0005390 9.28 AMBN CNNM4 DLX2 DLX5 ENAM FAM20A

Drugs & Therapeutics for Trichodentoosseous Syndrome

Search Clinical Trials , NIH Clinical Center for Trichodentoosseous Syndrome

Cochrane evidence based reviews: tricho-dento-osseous syndrome

Genetic Tests for Trichodentoosseous Syndrome

Genetic tests related to Trichodentoosseous Syndrome:

# Genetic test Affiliating Genes
1 Tricho-Dento-Osseous Syndrome 29 DLX3

Anatomical Context for Trichodentoosseous Syndrome

MalaCards organs/tissues related to Trichodentoosseous Syndrome:

40
Bone, Skin

Publications for Trichodentoosseous Syndrome

Articles related to Trichodentoosseous Syndrome:

(show top 50) (show all 59)
# Title Authors PMID Year
1
DLX3 c.561_562delCT mutation causes attenuated phenotype of tricho-dento-osseous syndrome. 6 56 61 54
18203197 2008
2
DLX3 mutation associated with autosomal dominant amelogenesis imperfecta with taurodontism. 61 56 6
15666299 2005
3
A common DLX3 gene mutation is responsible for tricho-dento-osseous syndrome in Virginia and North Carolina families. 56 6 61
9783705 1998
4
Identification of a mutation in DLX3 associated with tricho-dento-osseous (TDO) syndrome. 56 6 61
9467018 1998
5
Craniofacial variations in the tricho-dento-osseous syndrome. 56 61
22671030 2013
6
Tricho-dento-osseous syndrome and amelogenesis imperfecta with taurodontism are genetically distinct conditions. 61 56
10466415 1999
7
Genetic linkage of the tricho-dento-osseous syndrome to chromosome 17q21. 56 61
9361034 1997
8
Analysis of the tricho-dento-osseous syndrome genotype and phenotype. 56 61
9382143 1997
9
Amelogenesis imperfecta with taurodontism and the tricho-dento-osseous syndrome: separate conditions or a spectrum of disease? 61 56
2387085 1990
10
Tricho-dento-osseous syndrome: heterogeneity or clinical variability. 56 61
6650567 1983
11
Clinical heterogeneity in the tricho-dento-osseous syndrome. 56 61
6885044 1983
12
Amelogenesis imperfecta with taurodontism. 56 61
292959 1979
13
Tricho-dento-osseous syndrome: a scanning electron microscopic analysis. 61 56
891005 1977
14
Taurodontism of the mandibular first permanent molar distinguishes between the tricho-dento-osseous (TDO) syndrome and amelogenesis imperfecta. 56
8375104 1993
15
Amelogenesis imperfecta: autosomal dominant hypomaturation-hypoplasia type with taurodontism. 56
3422811 1988
16
The tricho-dento-osseous (TDO) syndrome. 56
5054226 1972
17
Hereditary amelogenesis imperfecta. A rare autosomal dominant type. 56
5258202 1969
18
Hereditary enamel hypoplasia: its association with characteristic hair structure. 56
5906373 1966
19
Molecular consequences of a frameshifted DLX3 mutant leading to Tricho-Dento-Osseous syndrome. 61 54
18492670 2008
20
A 4 bp deletion mutation in DLX3 enhances osteoblastic differentiation and bone formation in vitro. 54 61
17950683 2008
21
Trichodentoosseous syndrome: a case report and review of literature. 61
31938567 2019
22
17q21.32-q22 Deletion in a girl with osteogenesis imperfecta, tricho-dento-osseous syndrome, and intellectual disability. 61
29896840 2019
23
Novel DLX3 variants in amelogenesis imperfecta with attenuated tricho-dento-osseous syndrome. 61
30095208 2019
24
A de novo germline mutation of DLX3 in a Brown Swiss calf with tricho-dento-osseus-like syndrome. 61
28670783 2017
25
DLX3 interacts with GCM1 and inhibits its transactivation-stimulating activity in a homeodomain-dependent manner in human trophoblast-derived cells. 61
28515447 2017
26
Tricho-dento-osseous syndrome and precocious eruption. 61
28298997 2017
27
Senescence: novel insight into DLX3 mutations leading to enhanced bone formation in Tricho-Dento-Osseous syndrome. 61
27924851 2016
28
Morphological analyses and a novel de novo DLX3 mutation associated with tricho-dento-osseous syndrome in a Chinese family. 61
26104267 2015
29
Transcriptional factor DLX3 promotes the gene expression of enamel matrix proteins during amelogenesis. 61
25815730 2015
30
Interradicular dentin dysplasia associated with amelogenesis imperfecta with taurodontism or trichodentoosseous syndrome: a diagnostic dilemma. 61
24992867 2014
31
Periodontal management and restoration of an amelogenesis imperfecta patient: a case report. 61
24571544 2014
32
Osteogenesis imperfecta, tricho-dento-osseous syndrome and intellectual disability: a familial case with 17q21.33-q22 (COL1A1 and DLX3) deletion and 7q32.3-q33 duplication resulting from a reciprocal interchromosomal insertion. 61
23949819 2013
33
Tricho-dento-osseous syndrome: diagnosis and dental management. 61
22969805 2012
34
A dominant mutation etiologic for human tricho-dento-osseous syndrome impairs the ability of DLX3 to downregulate ΔNp63α. 61
21520071 2011
35
DLX3 homeodomain mutations cause tricho-dento-osseous syndrome with novel phenotypes. 61
21252474 2011
36
Systemic disorders and their influence on the development of dental hard tissues: a literature review. 61
20004698 2010
37
Uncombable hair and atopic dermatitis in a case of trichodento-osseous syndrome. 61
20151948 2010
38
In vivo impact of a 4 bp deletion mutation in the DLX3 gene on bone development. 61
18996110 2009
39
Dlx3 is a crucial regulator of hair follicle differentiation and cycling. 54
18684741 2008
40
DLX3 mutation in a new family and its phenotypic variations. 61
18362318 2008
41
A patient with melorheostosis manifesting with features similar to tricho-dento-osseous syndrome: a case report. 61
18284671 2008
42
Severely hypoplastic amelogenesis imperfecta with taurodontism. 61
17559453 2007
43
Expression pattern of Dlx3 during cell differentiation in mineralized tissues. 61
16172034 2005
44
Clinical features of tricho-dento-osseous syndrome and presentation of three new cases: an addition to clinical heterogeneity. 61
16301156 2005
45
Increased bone density associated with DLX3 mutation in the tricho-dento-osseous syndrome. 61
15454107 2004
46
Characterization and mRNA expression in an unusual odontogenic lesion in a patient with tricho-dento-osseous syndrome. 61
12792897 2003
47
[Tricho-dento-osseous syndrome]. 61
11529001 2001
48
Structural hair shaft abnormalities in hypomelanosis of ito and other ectodermal dysplasias. 61
10852202 2000
49
Comparative study of MSX-2, DLX-5, and DLX-7 gene expression during early human tooth development. 61
10590019 1999
50
Comparative mapping of distal murine chromosome 11 and human 17q21.3 in a region containing a modifying locus for murine plasma von Willebrand factor level. 61
9806826 1998

Variations for Trichodentoosseous Syndrome

ClinVar genetic disease variations for Trichodentoosseous Syndrome:

6 ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 DLX3 NM_005220.3(DLX3):c.574del (p.Glu192fs)deletion Pathogenic 430607 rs1057518764 17:48069171-48069171 17:49991807-49991807
2 DLX3 NM_005220.3(DLX3):c.476G>T (p.Arg159Leu)SNV Pathogenic 430609 rs1555617226 17:48070804-48070804 17:49993440-49993440
3 DLX3 NM_005220.3(DLX3):c.571_574del (p.Gly191fs)deletion Pathogenic 9072 rs387906405 17:48069171-48069174 17:49991807-49991810
4 DLX3 NM_005220.3(DLX3):c.559_560CT[1] (p.Tyr188fs)short repeat Pathogenic 9073 rs387906406 17:48069183-48069184 17:49991819-49991820
5 DLX3 NM_005220.3(DLX3):c.337_339GAG[1] (p.Glu114del)short repeat Uncertain significance 800783 17:48070938-48070940 17:49993574-49993576

Expression for Trichodentoosseous Syndrome

Search GEO for disease gene expression data for Trichodentoosseous Syndrome.

Pathways for Trichodentoosseous Syndrome

GO Terms for Trichodentoosseous Syndrome

Cellular components related to Trichodentoosseous Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 extracellular region GO:0005576 9.7 ODAPH MMP25 MMP20 FAM20A ENAM DSPP
2 nuclear chromatin GO:0000790 9.35 MSX2 DLX5 DLX4 DLX3 DLX2
3 extracellular matrix GO:0031012 8.92 MMP25 MMP20 ENAM DSPP

Biological processes related to Trichodentoosseous Syndrome according to GeneCards Suite gene sharing:

(show all 11)
# Name GO ID Score Top Affiliating Genes
1 multicellular organism development GO:0007275 9.93 MSX2 DSPP DLX5 DLX4 DLX3 DLX2
2 ossification GO:0001503 9.61 MSX2 DSPP DLX5
3 odontogenesis of dentin-containing tooth GO:0042475 9.56 ENAM DLX3 DLX2 AMBN
4 collagen catabolic process GO:0030574 9.49 MMP25 MMP20
5 bone morphogenesis GO:0060349 9.48 MSX2 DLX5
6 embryo development GO:0009790 9.46 DLX5 DLX4 DLX3 DLX2
7 amelogenesis GO:0097186 9.4 MMP20 ENAM
8 odontoblast differentiation GO:0071895 9.37 DSPP DLX3
9 positive regulation of enamel mineralization GO:0070175 9.32 ODAPH ENAM
10 enamel mineralization GO:0070166 9.26 WDR72 MSX2 FAM20A CNNM4
11 biomineral tissue development GO:0031214 9.17 WDR72 FAM83H FAM20A ENAM DSPP CNNM4

Molecular functions related to Trichodentoosseous Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 DNA-binding transcription factor activity, RNA polymerase II-specific GO:0000981 9.55 MSX2 DLX5 DLX4 DLX3 DLX2
2 sequence-specific DNA binding GO:0043565 9.35 MSX2 DLX5 DLX4 DLX3 DLX2
3 structural constituent of tooth enamel GO:0030345 8.62 ENAM AMBN

Sources for Trichodentoosseous Syndrome

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
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
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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