ECTD3
MCID: WTK002
MIFTS: 35

Witkop Syndrome (ECTD3)

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

Aliases & Classifications for Witkop Syndrome

MalaCards integrated aliases for Witkop Syndrome:

Name: Witkop Syndrome 58 77 54 60 76 45
Tooth and Nail Syndrome 12 54 60 38 15
Hypoplastic Enamel-Onycholysis-Hypohidrosis Syndrome 12 30 6 74
Ectodermal Dysplasia 3, Witkop Type 58 76 13
Tns 58 54 76
Ectodermal Dysplasia 3, Tooth/nail Type 58 76
Dysplasia of Nails with Hypodontia 54 76
Tooth-and-Nail Syndrome 58 76
Ectd3 58 76
Ectodermal Dysplasia 3, Witkop Type; Ectd3 58
Hypodontia-Dysplasia of Nails Syndrome 60
Hypodontia-Nail Dysgenesis Syndrome 60
Hypodontia - Dysplasia of Nails 54
Nail Dysplasia with Hypodontia 58
Tooth-and-Nail Syndrome; Tns 58
Hypodontia-Nail Dysgenesis 76
Witkop's Syndrome 12

Characteristics:

Orphanet epidemiological data:

60
hypodontia-dysplasia of nails syndrome
Inheritance: Autosomal dominant; Age of onset: Childhood; Age of death: normal life expectancy;

OMIM:

58
Inheritance:
autosomal dominant

Miscellaneous:
estimated incidence of 1-2 in 10,000
normal ability to tolerate heat
thin, fine hair described in few individuals


HPO:

33
witkop syndrome:
Inheritance autosomal dominant inheritance


Classifications:



External Ids:

Disease Ontology 12 DOID:6678
OMIM 58 189500
KEGG 38 H00643
NCIt 51 C40553
SNOMED-CT 69 68897000
ICD10 via Orphanet 35 Q82.4
UMLS via Orphanet 75 C0406716 C0406735
Orphanet 60 ORPHA2228
MedGen 43 C0406735
UMLS 74 C0406735

Summaries for Witkop Syndrome

NIH Rare Diseases : 54 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 2228Disease definitionHypodontia-nail dysplasia syndrome is a form of ectodermal dysplasia.EpidemiologyIts incidence has been estimated at around 1-2 in 10,000.Clinical descriptionThe primary teeth are usually normal but the permanent teeth often fail to erupt. The mandibular incisors, second molars, and maxillary canines are frequently absent and the crowns may be small and conical. Lip eversion may be present. Nails are usually small, thin and brittle with longitudinal ridges, pitting and koilonychias. Congenital absence of the nail plate has also been reported. Toenails are usually more severely affected than fingernails. Sweat glands, heat tolerance and hair are normal, although fine hair has been described in some cases.EtiologyThe syndrome is caused by a mutation in the MSX1 gene (4p16.1).Diagnostic methodsDiagnosis is usually made during mid-childhood when persistence of the primary dentition becomes apparent, but the syndrome may be difficult to diagnose as the nail defects may be mild.Differential diagnosisThe differential diagnosis should include other forms of ectodermal dysplasia, in particular hypohidrotic ectodermal dysplasia (see these terms).Genetic counselingTransmission is autosomal dominant.Management and treatmentThere is no specific treatment but oral health care and dental management are recommended.PrognosisThe prognosis is good. The nail defects usually become less apparent with age and the nails often appear normal by adulthood.Visit the Orphanet disease page for more resources.

MalaCards based summary : Witkop Syndrome, also known as tooth and nail syndrome, is related to tn polyagglutination syndrome and trigeminal neuralgia, and has symptoms including koilonychia An important gene associated with Witkop Syndrome is MSX1 (Msh Homeobox 1). Affiliated tissues include skin, ovary and colon, and related phenotypes are delayed eruption of teeth and hypoplastic toenails

Disease Ontology : 12 A syndrome that affects the teeth, nails, hair, and/or skin. It is characterized by absence (hypodontia) and/or malformation of certain primary (deciduous) and secondary (permanent) teeth occurring in association with improper development of the nails, particularly the toenails.

OMIM : 58 Some ectodermal dysplasias are here classified as congenital disorders characterized by abnormal development in 2 or more ectodermal structures (hair, nails, teeth, and sweat glands) without other systemic findings. Witkop syndrome is a rare autosomal dominant ectodermal dysplasia involving the teeth and nails. Although a few reported cases have sparse or fine hair, almost all affected individuals have normal hair, sweat glands, and ability to tolerate heat. Affected individuals have a variable number and variable types of congenitally missing permanent and/or primary teeth, which frequently results in lip eversion due to loss of occlusion in the vertical dimension. Nails are generally thin, slow-growing, brittle, and spoon-shaped (koilonychia). Toenails are usually more severely affected than fingernails. The nail defects are alleviated with age and may not be easily detectable during adulthood (summary by Jumlongras et al., 2001). (189500)

UniProtKB/Swiss-Prot : 76 Ectodermal dysplasia 3, Witkop type: A form of ectodermal dysplasia, a heterogeneous group of disorders due to abnormal development of two or more ectodermal structures such as hair, teeth, nails and sweat glands, with or without any additional clinical sign. Each combination of clinical features represents a different type of ectodermal dysplasia. ECTD3 is characterized by abnormalities largely limited largely to teeth (some of which are missing) and nails (which are poorly formed early in life, especially toenails). This condition is distinguished from anhidrotic ectodermal dysplasia by autosomal dominant inheritance and little involvement of hair and sweat glands. The teeth are not as severely affected.

Wikipedia : 77 Tooth and nail syndrome (also known as "Hypodontia with nail dysgenesis," and "Witkop syndrome") is a... more...

Related Diseases for Witkop Syndrome

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

(show top 50) (show all 77)
# Related Disease Score Top Affiliating Genes
1 tn polyagglutination syndrome 12.8
2 trigeminal neuralgia 11.9
3 ectodermal dysplasia 8, hair/tooth/nail type 11.4
4 thoracic outlet syndrome 11.1
5 breast cancer 10.3
6 colorectal cancer 10.3
7 gastric cancer 10.2
8 depression 10.2
9 ovarian cancer 10.2
10 major depressive disorder 10.2
11 mental depression 10.2
12 adenocarcinoma 10.1
13 nail disorder, nonsyndromic congenital, 9 10.1
14 bladder cancer 10.0
15 ovarian cancer 1 10.0
16 gastritis 10.0
17 mucoepidermoid carcinoma 10.0
18 tylosis with esophageal cancer 10.0
19 raine syndrome 10.0
20 retinitis pigmentosa 10.0
21 helicobacter pylori infection 10.0
22 salla disease 10.0
23 west nile virus 10.0
24 cholera 10.0
25 lynch syndrome 10.0
26 fibromyalgia 10.0
27 esophageal cancer 9.8
28 meniere disease 9.8
29 mesothelioma, malignant 9.8
30 carney complex, type 1 9.8
31 prostate cancer 9.8
32 ataxia-telangiectasia 9.8
33 disorganization, mouse, homolog of 9.8
34 myelofibrosis 9.8
35 pancreatic cancer 9.8
36 insulin-like growth factor i 9.8
37 prostate cancer, hereditary, 8 9.8
38 caronte 9.8
39 anxiety 9.8
40 endometrial cancer 9.8
41 myocardial infarction 9.8
42 prostate cancer, hereditary, 6 9.8
43 mungan syndrome 9.8
44 microcephaly, epilepsy, and diabetes syndrome 9.8
45 myelodysplastic syndrome 9.8
46 melioidosis 9.8
47 colorectal adenoma 9.8
48 keratopathy 9.8
49 leukemia 9.8
50 neutropenia 9.8

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



Diseases related to Witkop Syndrome

Symptoms & Phenotypes for Witkop Syndrome

Human phenotypes related to Witkop Syndrome:

60 33 (show all 22)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 delayed eruption of teeth 60 33 hallmark (90%) Very frequent (99-80%) HP:0000684
2 hypoplastic toenails 60 33 hallmark (90%) Very frequent (99-80%) HP:0001800
3 hypodontia 60 33 hallmark (90%) Very frequent (99-80%) HP:0000668
4 hypoplastic fingernail 60 33 hallmark (90%) Very frequent (99-80%) HP:0001804
5 ridged fingernail 60 33 hallmark (90%) Very frequent (99-80%) HP:0008402
6 fragile nails 60 33 hallmark (90%) Very frequent (99-80%) HP:0001808
7 conical tooth 60 33 hallmark (90%) Very frequent (99-80%) HP:0000698
8 agenesis of permanent teeth 60 33 hallmark (90%) Very frequent (99-80%) HP:0006349
9 thin toenail 60 33 hallmark (90%) Very frequent (99-80%) HP:0012746
10 everted lower lip vermilion 60 33 frequent (33%) Frequent (79-30%) HP:0000232
11 fine hair 60 33 frequent (33%) Frequent (79-30%) HP:0002213
12 polycystic ovaries 60 33 occasional (7.5%) Occasional (29-5%) HP:0000147
13 abnormality of the dentition 60 Very frequent (99-80%)
14 abnormality of the nail 60 Very frequent (99-80%)
15 abnormality of the fingernails 60 Very frequent (99-80%)
16 small nail 33 HP:0001792
17 abnormality of dental morphology 60 Very frequent (99-80%)
18 sparse hair 33 HP:0008070
19 nail pits 33 HP:0001803
20 ridged nail 33 HP:0001807
21 concave nail 33 HP:0001598
22 microdontia of primary teeth 33 HP:0006347

Symptoms via clinical synopsis from OMIM:

58
Skin Nails Hair Nails:
nail pits
koilonychia
longitudinal ridging
thin, small friable nails
toenails often more affected than fingernails
more
Head And Neck Face:
normal facies

Head And Neck Teeth:
normal to small primary teeth
partial to total absence of permanent teeth

Skin Nails Hair Hair:
normal hair

Head And Neck Mouth:
lip eversion

Skin Nails Hair Skin:
normal sweat glands

Clinical features from OMIM:

189500

UMLS symptoms related to Witkop Syndrome:


koilonychia

Drugs & Therapeutics for Witkop Syndrome

Search Clinical Trials , NIH Clinical Center for Witkop Syndrome

Cochrane evidence based reviews: witkop syndrome

Genetic Tests for Witkop Syndrome

Genetic tests related to Witkop Syndrome:

# Genetic test Affiliating Genes
1 Hypoplastic Enamel-Onycholysis-Hypohidrosis Syndrome 30 MSX1

Anatomical Context for Witkop Syndrome

MalaCards organs/tissues related to Witkop Syndrome:

42
Skin, Ovary, Colon, Bone Marrow, Myeloid

Publications for Witkop Syndrome

Articles related to Witkop Syndrome:

(show all 14)
# Title Authors Year
1
MSX1 mutation in witkop syndrome; a case report. ( 24031111 )
2013
2
Witkop syndrome: A case report of an affected family. ( 22747926 )
2012
3
Witkop tooth and nail syndrome: a report of three cases in a family. ( 21054511 )
2011
4
Reduced systemic bone mineral density associated with a rare case of tooth and nail syndrome. ( 20371434 )
2010
5
Witkop tooth and nail syndrome and orthodontics. ( 18251614 )
2008
6
Witkop's tooth and nail syndrome: a multifaceted approach to dental management. ( 18408267 )
2008
7
Witkop tooth and nail syndrome: a case report. ( 16129001 )
2005
8
Dental implications of Tooth-Nail dysplasia (Witkop syndrome): a report of an affected family and an approach to dental management. ( 14969367 )
2004
9
A nonsense mutation in MSX1 causes Witkop syndrome. ( 11369996 )
2001
10
Hereditary hypodontia and onychorrhexis of the fingernails and toenail koilonychia: Witkop's tooth-and nail syndrome. ( 10673446 )
1999
11
Witkop tooth and nail syndrome: report of two cases in a family. ( 10815578 )
1999
12
Features of oligodontia in three generations. ( 9484139 )
1997
13
What syndrome is this? Witkop tooth and nail syndrome. ( 8919531 )
1996
14
Tooth and nail syndrome: genetic, clinical and dermatoglyphic findings: case report. ( 8466837 )
1993

Variations for Witkop Syndrome

ClinVar genetic disease variations for Witkop Syndrome:

6 (show all 26)
# Gene Variation Type Significance SNP ID Assembly Location
1 MSX1 NM_002448.3(MSX1): c.623C> A (p.Ser208Ter) single nucleotide variant Pathogenic rs104893853 GRCh37 Chromosome 4, 4864581: 4864581
2 MSX1 NM_002448.3(MSX1): c.623C> A (p.Ser208Ter) single nucleotide variant Pathogenic rs104893853 GRCh38 Chromosome 4, 4862854: 4862854
3 MSX1 NM_002448.3(MSX1): c.123C> A (p.Ala41=) single nucleotide variant Likely benign rs1001828551 GRCh37 Chromosome 4, 4861749: 4861749
4 MSX1 NM_002448.3(MSX1): c.123C> A (p.Ala41=) single nucleotide variant Likely benign rs1001828551 GRCh38 Chromosome 4, 4860022: 4860022
5 MSX1 NM_002448.3(MSX1): c.365G> T (p.Gly122Val) single nucleotide variant Uncertain significance rs28933081 GRCh38 Chromosome 4, 4860264: 4860264
6 MSX1 NM_002448.3(MSX1): c.365G> T (p.Gly122Val) single nucleotide variant Uncertain significance rs28933081 GRCh37 Chromosome 4, 4861991: 4861991
7 MSX1 NM_002448.3(MSX1): c.86C> T (p.Ala29Val) single nucleotide variant Benign rs530217423 GRCh38 Chromosome 4, 4859985: 4859985
8 MSX1 NM_002448.3(MSX1): c.86C> T (p.Ala29Val) single nucleotide variant Benign rs530217423 GRCh37 Chromosome 4, 4861712: 4861712
9 MSX1 NM_002448.3(MSX1): c.324G> T (p.Ala108=) single nucleotide variant Likely benign rs574606351 GRCh37 Chromosome 4, 4861950: 4861950
10 MSX1 NM_002448.3(MSX1): c.324G> T (p.Ala108=) single nucleotide variant Likely benign rs574606351 GRCh38 Chromosome 4, 4860223: 4860223
11 MSX1 NM_002448.3(MSX1): c.561G> A (p.Leu187=) single nucleotide variant Benign rs149960650 GRCh38 Chromosome 4, 4862792: 4862792
12 MSX1 NM_002448.3(MSX1): c.561G> A (p.Leu187=) single nucleotide variant Benign rs149960650 GRCh37 Chromosome 4, 4864519: 4864519
13 MSX1 NM_002448.3(MSX1): c.89G> C (p.Gly30Ala) single nucleotide variant Uncertain significance rs1414674827 GRCh38 Chromosome 4, 4859988: 4859988
14 MSX1 NM_002448.3(MSX1): c.89G> C (p.Gly30Ala) single nucleotide variant Uncertain significance rs1414674827 GRCh37 Chromosome 4, 4861715: 4861715
15 MSX1 NM_002448.3(MSX1): c.127A> C (p.Met43Leu) single nucleotide variant Benign rs565664559 GRCh37 Chromosome 4, 4861753: 4861753
16 MSX1 NM_002448.3(MSX1): c.127A> C (p.Met43Leu) single nucleotide variant Benign rs565664559 GRCh38 Chromosome 4, 4860026: 4860026
17 MSX1 NM_002448.3(MSX1): c.661C> T (p.Gln221Ter) single nucleotide variant Pathogenic rs1553878162 GRCh38 Chromosome 4, 4862892: 4862892
18 MSX1 NM_002448.3(MSX1): c.661C> T (p.Gln221Ter) single nucleotide variant Pathogenic rs1553878162 GRCh37 Chromosome 4, 4864619: 4864619
19 MSX1 NM_002448.3(MSX1): c.752_753delTCinsAA (p.Phe251Ter) indel Uncertain significance rs1553878166 GRCh37 Chromosome 4, 4864710: 4864711
20 MSX1 NM_002448.3(MSX1): c.752_753delTCinsAA (p.Phe251Ter) indel Uncertain significance rs1553878166 GRCh38 Chromosome 4, 4862983: 4862984
21 MSX1 NM_002448.3(MSX1): c.*276A> G single nucleotide variant Benign rs12532 GRCh37 Chromosome 4, 4865146: 4865146
22 MSX1 NM_002448.3(MSX1): c.*276A> G single nucleotide variant Benign rs12532 GRCh38 Chromosome 4, 4863419: 4863419
23 MSX1 NM_002448.3(MSX1): c.95C> T (p.Ala32Val) single nucleotide variant Uncertain significance GRCh37 Chromosome 4, 4861721: 4861721
24 MSX1 NM_002448.3(MSX1): c.95C> T (p.Ala32Val) single nucleotide variant Uncertain significance GRCh38 Chromosome 4, 4859994: 4859994
25 MSX1 NM_002448.3(MSX1): c.310G> C (p.Gly104Arg) single nucleotide variant Uncertain significance GRCh37 Chromosome 4, 4861936: 4861936
26 MSX1 NM_002448.3(MSX1): c.310G> C (p.Gly104Arg) single nucleotide variant Uncertain significance GRCh38 Chromosome 4, 4860209: 4860209

Expression for Witkop Syndrome

Search GEO for disease gene expression data for Witkop Syndrome.

Pathways for Witkop Syndrome

GO Terms for Witkop Syndrome

Sources for Witkop Syndrome

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
20 FMA
29 GO
30 GTR
31 HGMD
32 HMDB
33 HPO
34 ICD10
35 ICD10 via Orphanet
36 ICD9CM
37 IUPHAR
38 KEGG
39 LifeMap
41 LOVD
43 MedGen
45 MeSH
46 MESH via Orphanet
47 MGI
50 NCI
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52 NDF-RT
55 NINDS
56 Novoseek
58 OMIM
59 OMIM via Orphanet
63 PubMed
65 QIAGEN
70 SNOMED-CT via HPO
71 SNOMED-CT via Orphanet
72 TGDB
73 Tocris
74 UMLS
75 UMLS via Orphanet
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