ECTD3
MCID: WTK002
MIFTS: 43

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 57 73 20 58 72 44
Tooth and Nail Syndrome 12 20 58 36 15
Hypoplastic Enamel-Onycholysis-Hypohidrosis Syndrome 12 29 6 70
Ectodermal Dysplasia 3, Witkop Type 57 72 13
Tns 57 20 72
Ectodermal Dysplasia 3, Tooth/nail Type 57 72
Dysplasia of Nails with Hypodontia 20 72
Tooth-and-Nail Syndrome 57 72
Ectd3 57 72
Ectodermal Dysplasia 3, Witkop Type; Ectd3 57
Hypodontia-Dysplasia of Nails Syndrome 58
Hypodontia-Nail Dysgenesis Syndrome 58
Hypodontia - Dysplasia of Nails 20
Nail Dysplasia with Hypodontia 57
Tooth-and-Nail Syndrome; Tns 57
Hypodontia-Nail Dysgenesis 72
Witkop's Syndrome 12

Characteristics:

Orphanet epidemiological data:

58
hypodontia-dysplasia of nails syndrome
Inheritance: Autosomal dominant; Age of onset: Childhood; Age of death: normal life expectancy;

OMIM®:

57 (Updated 20-May-2021)
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:

31
witkop syndrome:
Inheritance autosomal dominant inheritance


Classifications:

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


External Ids:

Disease Ontology 12 DOID:6678
OMIM® 57 189500
OMIM Phenotypic Series 57 PS305100
KEGG 36 H00643
NCIt 50 C40553
SNOMED-CT 67 400036004
ICD10 via Orphanet 33 Q82.4
UMLS via Orphanet 71 C0406716 C0406735
Orphanet 58 ORPHA2228
MedGen 41 C0406735
UMLS 70 C0406735

Summaries for Witkop Syndrome

GARD : 20 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs. Orpha Number: 2228 Definition Hypodontia-nail dysplasia syndrome is a form of ectodermal dysplasia. Epidemiology Its incidence has been estimated at around 1-2 in 10,000. Clinical description The 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. Etiology The syndrome is caused by a mutation in the MSX1 gene (4p16.1). Diagnostic methods Diagnosis 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 diagnosis The differential diagnosis should include other forms of ectodermal dysplasia, in particular hypohidrotic ectodermal dysplasia (see these terms). Genetic counseling Transmission is autosomal dominant. Management and treatment There is no specific treatment but oral health care and dental management are recommended. Prognosis The prognosis is good. The nail defects usually become less apparent with age and the nails often appear normal by adulthood.

MalaCards based summary : Witkop Syndrome, also known as tooth and nail syndrome, is related to anodontia and ectodermal dysplasia 8, hair/tooth/nail type, and has symptoms including koilonychia An important gene associated with Witkop Syndrome is MSX1 (Msh Homeobox 1), and among its related pathways/superpathways is Elastic fibre formation. Affiliated tissues include bone, and related phenotypes are hypoplastic toenails and delayed eruption of teeth

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® : 57 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) (Updated 20-May-2021)

KEGG : 36 Witkop syndrome, also known as tooth and nail syndrome, is a form of ectodermal dysplasia manifested by hypodontia and nail dysplasia. Several teeth are congenitally missing and nails are spoon-shaped and easily broken. Mutations are identified in MSX1 gene.

UniProtKB/Swiss-Prot : 72 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 : 73 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 66)
# Related Disease Score Top Affiliating Genes
1 anodontia 29.5 PAX9 MSX1 EDAR
2 ectodermal dysplasia 8, hair/tooth/nail type 11.4
3 major depressive disorder 10.3
4 mental depression 10.3
5 depression 10.3
6 nail disorder, nonsyndromic congenital, 9 10.2
7 placental insufficiency 10.2
8 syngnathia 10.1 MSX1 BARX1
9 anxiety 10.0
10 fibromyalgia 10.0
11 back pain 10.0
12 chronic pain 10.0
13 ectodermal dysplasia 10.0
14 geleophysic dysplasia 3 10.0 LTBP3 LTBP2
15 geleophysic dysplasia 10.0 LTBP3 LTBP2
16 excessive tearing 10.0 LTBP3 LTBP2
17 geleophysic dysplasia 1 10.0 LTBP3 LTBP2
18 geleophysic dysplasia 2 9.9 LTBP3 LTBP2
19 hydrophthalmos 9.9 LTBP3 LTBP2
20 tooth size 9.9 PAX9 MSX1
21 phacogenic glaucoma 9.9 LTBP3 LTBP2
22 autosomal recessive cutis laxa type i 9.9 LTBP3 LTBP2
23 tooth agenesis, selective, 1 9.9 PAX9 MSX1
24 brachyolmia 9.9 LTBP3 LTBP2
25 acromicric dysplasia 9.9 LTBP3 LTBP2
26 megalocornea 9.9 LTBP3 LTBP2
27 camurati-engelmann disease 9.9 LTBP3 LTBP2
28 iris disease 9.9 LTBP3 LTBP2
29 juvenile glaucoma 9.9 LTBP3 LTBP2
30 isolated ectopia lentis 9.9 LTBP3 LTBP2
31 primary congenital glaucoma 9.9 LTBP3 LTBP2
32 weill-marchesani syndrome 9.9 LTBP3 LTBP2
33 ectodermal dysplasia 10b 9.9 PAX9 EDAR
34 van der woude syndrome 1 9.9 PAX9 MSX1
35 glaucoma 3, primary congenital, a 9.9 LTBP3 LTBP2
36 migraine with or without aura 1 9.8
37 rheumatoid arthritis 9.8
38 schizophrenia 9.8
39 stroke, ischemic 9.8
40 pulmonary disease, chronic obstructive 9.8
41 neutropenia 9.8
42 generalized anxiety disorder 9.8
43 post-traumatic stress disorder 9.8
44 peripheral nervous system disease 9.8
45 panic disorder 9.8
46 acute stress disorder 9.8
47 arthritis 9.8
48 neuropathy 9.8
49 irritable bowel syndrome 9.8
50 headache 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:

58 31 (show all 22)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 hypoplastic toenails 58 31 hallmark (90%) Very frequent (99-80%) HP:0001800
2 delayed eruption of teeth 58 31 hallmark (90%) Very frequent (99-80%) HP:0000684
3 hypodontia 58 31 hallmark (90%) Very frequent (99-80%) HP:0000668
4 hypoplastic fingernail 58 31 hallmark (90%) Very frequent (99-80%) HP:0001804
5 ridged fingernail 58 31 hallmark (90%) Very frequent (99-80%) HP:0008402
6 fragile nails 58 31 hallmark (90%) Very frequent (99-80%) HP:0001808
7 conical tooth 58 31 hallmark (90%) Very frequent (99-80%) HP:0000698
8 agenesis of permanent teeth 58 31 hallmark (90%) Very frequent (99-80%) HP:0006349
9 thin toenail 58 31 hallmark (90%) Very frequent (99-80%) HP:0012746
10 everted lower lip vermilion 58 31 frequent (33%) Frequent (79-30%) HP:0000232
11 fine hair 58 31 frequent (33%) Frequent (79-30%) HP:0002213
12 polycystic ovaries 58 31 occasional (7.5%) Occasional (29-5%) HP:0000147
13 abnormality of the dentition 58 Very frequent (99-80%)
14 abnormality of the nail 58 Very frequent (99-80%)
15 abnormal fingernail morphology 58 Very frequent (99-80%)
16 abnormality of dental morphology 58 Very frequent (99-80%)
17 sparse hair 31 HP:0008070
18 concave nail 31 HP:0001598
19 ridged nail 31 HP:0001807
20 nail pits 31 HP:0001803
21 small nail 31 HP:0001792
22 microdontia of primary teeth 31 HP:0006347

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
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 (Updated 20-May-2021)

UMLS symptoms related to Witkop Syndrome:


koilonychia

MGI Mouse Phenotypes related to Witkop Syndrome:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 craniofacial MP:0005382 9.8 BARX1 DLX1 EDAR LTBP3 MSX1 PAX9
2 mortality/aging MP:0010768 9.7 BARX1 DLX1 EDAR LTBP2 LTBP3 MSX1
3 digestive/alimentary MP:0005381 9.65 BARX1 DLX1 EDAR MSX1 PAX9
4 respiratory system MP:0005388 9.26 LTBP2 LTBP3 MSX1 PAX9
5 skeleton MP:0005390 9.02 DLX1 EDAR LTBP3 MSX1 PAX9

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 29 MSX1

Anatomical Context for Witkop Syndrome

MalaCards organs/tissues related to Witkop Syndrome:

40
Bone

Publications for Witkop Syndrome

Articles related to Witkop Syndrome:

(show all 23)
# Title Authors PMID Year
1
A nonsense mutation in MSX1 causes Witkop syndrome. 6 61 57
11369996 2001
2
Dental implications of Tooth-Nail dysplasia (Witkop syndrome): a report of an affected family and an approach to dental management. 57 61
14969367 2004
3
Features of oligodontia in three generations. 61 6
9484139 1997
4
Candidate gene analysis of tooth agenesis identifies novel mutations in six genes and suggests significant role for WNT and EDA signaling and allele combinations. 6
23991204 2013
5
Recessive anonychia totalis and dominant aplasis (or hypoplasia) of upper lateral incisors in the same kindred. 57
469885 1979
6
Autosomal dominant hypodontia with nail dysgenesis. Report of twenty-nine cases in six families. 57
1054139 1975
7
The "tooth and nail" type of autosomal dominant ectodermal dysplasia. 57
4521949 1974
8
Autosomal dominant ectodermal dysplasia with significant dental defects. 57
5254120 1969
9
Autosomal dominant mutation of MSX1 gene causing tooth and nail syndrome. 61
33708320 2020
10
MSX1 mutation in witkop syndrome; a case report. 61
24031111 2013
11
Witkop syndrome: A case report of an affected family. 61
22747926 2012
12
Witkop tooth and nail syndrome: a report of three cases in a family. 61
21054511 2011
13
Reduced systemic bone mineral density associated with a rare case of tooth and nail syndrome. 61
20371434 2010
14
Witkop's tooth and nail syndrome: a multifaceted approach to dental management. 61
18408267 2008
15
Witkop tooth and nail syndrome and orthodontics. 61
18251614 2008
16
Witkop tooth and nail syndrome: a case report. 61
16129001 2005
17
Witkop tooth and nail syndrome: report of two cases in a family. 61
10815578 1999
18
Hereditary hypodontia and onychorrhexis of the fingernails and toenail koilonychia: Witkop's tooth-and nail syndrome. 61
10673446 1999
19
Hidrotic ectodermal dysplasia of hair, teeth, and nails: case reports and review. 61
8863167 1996
20
What syndrome is this? Witkop tooth and nail syndrome. 61
8919531 1996
21
Hypodontia and nail dysplasia syndrome. Report of a case. 61
8469557 1993
22
Tooth and nail syndrome: genetic, clinical and dermatoglyphic findings: case report. 61
8466837 1993
23
[Case report of the so-called tooth and nail syndrome]. 61
7168228 1982

Variations for Witkop Syndrome

ClinVar genetic disease variations for Witkop Syndrome:

6 (show all 26)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 MSX1 NM_002448.3(MSX1):c.661C>T (p.Gln221Ter) SNV Pathogenic 461602 rs1553878162 GRCh37: 4:4864619-4864619
GRCh38: 4:4862892-4862892
2 MSX1 NM_002448.3(MSX1):c.655_659del (p.Trp219fs) Deletion Pathogenic 845306 GRCh37: 4:4864613-4864617
GRCh38: 4:4862886-4862890
3 MSX1 NM_002448.3(MSX1):c.623C>A (p.Ser208Ter) SNV Pathogenic 14882 rs104893853 GRCh37: 4:4864581-4864581
GRCh38: 4:4862854-4862854
4 MSX1 NM_002448.3(MSX1):c.310G>C (p.Gly104Arg) SNV Uncertain significance 578158 rs768005654 GRCh37: 4:4861936-4861936
GRCh38: 4:4860209-4860209
5 MSX1 NM_002448.3(MSX1):c.752_753delinsAA (p.Phe251Ter) Indel Uncertain significance 461603 rs1553878166 GRCh37: 4:4864710-4864711
GRCh38: 4:4862983-4862984
6 MSX1 NM_002448.3(MSX1):c.581A>G (p.Lys194Arg) SNV Uncertain significance 947690 GRCh37: 4:4864539-4864539
GRCh38: 4:4862812-4862812
7 MSX1 NM_002448.3(MSX1):c.599C>T (p.Ala200Val) SNV Uncertain significance 982731 GRCh37: 4:4864557-4864557
GRCh38: 4:4862830-4862830
8 MSX1 NM_002448.3(MSX1):c.682_683del (p.Lys228fs) Deletion Uncertain significance 835937 GRCh37: 4:4864639-4864640
GRCh38: 4:4862912-4862913
9 MSX1 NM_002448.3(MSX1):c.623C>G (p.Ser208Trp) SNV Uncertain significance 1022700 GRCh37: 4:4864581-4864581
GRCh38: 4:4862854-4862854
10 MSX1 NM_002448.3(MSX1):c.670C>T (p.Arg224Cys) SNV Uncertain significance 1026068 GRCh37: 4:4864628-4864628
GRCh38: 4:4862901-4862901
11 MSX1 NM_002448.3(MSX1):c.796G>A (p.Ala266Thr) SNV Uncertain significance 1035233 GRCh37: 4:4864754-4864754
GRCh38: 4:4863027-4863027
12 MSX1 NM_002448.3(MSX1):c.89G>C (p.Gly30Ala) SNV Uncertain significance 461605 rs1414674827 GRCh37: 4:4861715-4861715
GRCh38: 4:4859988-4859988
13 MSX1 NM_002448.3(MSX1):c.365G>T (p.Gly122Val) SNV Uncertain significance 461600 rs28933081 GRCh37: 4:4861991-4861991
GRCh38: 4:4860264-4860264
14 MSX1 NM_002448.3(MSX1):c.102C>G (p.Ser34Arg) SNV Uncertain significance 647201 rs1349964186 GRCh37: 4:4861728-4861728
GRCh38: 4:4860001-4860001
15 MSX1 NM_002448.3(MSX1):c.65G>A (p.Gly22Asp) SNV Likely benign 772759 rs755151662 GRCh37: 4:4861691-4861691
GRCh38: 4:4859964-4859964
16 MSX1 NM_002448.3(MSX1):c.821C>T (p.Ala274Val) SNV Likely benign 800248 rs62636562 GRCh37: 4:4864779-4864779
GRCh38: 4:4863052-4863052
17 MSX1 NM_002448.3(MSX1):c.89G>A (p.Gly30Asp) SNV Likely benign 931187 GRCh37: 4:4861715-4861715
GRCh38: 4:4859988-4859988
18 MSX1 NM_002448.3(MSX1):c.95C>T (p.Ala32Val) SNV Likely benign 566634 rs771408025 GRCh37: 4:4861721-4861721
GRCh38: 4:4859994-4859994
19 MSX1 NM_002448.3(MSX1):c.561G>A (p.Leu187=) SNV Benign 461601 rs149960650 GRCh37: 4:4864519-4864519
GRCh38: 4:4862792-4862792
20 MSX1 NM_002448.3(MSX1):c.86C>T (p.Ala29Val) SNV Benign 461604 rs530217423 GRCh37: 4:4861712-4861712
GRCh38: 4:4859985-4859985
21 MSX1 NM_002448.3(MSX1):c.218C>T (p.Pro73Leu) SNV Benign 703022 rs201156596 GRCh37: 4:4861844-4861844
GRCh38: 4:4860117-4860117
22 MSX1 NM_002448.3(MSX1):c.471G>T (p.Arg157Ser) SNV Benign 225414 rs150284621 GRCh37: 4:4864429-4864429
GRCh38: 4:4862702-4862702
23 MSX1 NM_002448.3(MSX1):c.119C>G (p.Ala40Gly) SNV Benign 802050 rs36059701 GRCh37: 4:4861745-4861745
GRCh38: 4:4860018-4860018
24 MSX1 NM_002448.3(MSX1):c.127A>C (p.Met43Leu) SNV Benign 461595 rs565664559 GRCh37: 4:4861753-4861753
GRCh38: 4:4860026-4860026
25 MSX1 NM_002448.3(MSX1):c.151A>G (p.Lys51Glu) SNV Benign 800202 rs994158401 GRCh37: 4:4861777-4861777
GRCh38: 4:4860050-4860050
26 MSX1 NM_002448.3(MSX1):c.*276A>G SNV Benign 530788 rs12532 GRCh37: 4:4865146-4865146
GRCh38: 4:4863419-4863419

Expression for Witkop Syndrome

Search GEO for disease gene expression data for Witkop Syndrome.

Pathways for Witkop Syndrome

Pathways related to Witkop Syndrome according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
10.49 LTBP3 LTBP2

GO Terms for Witkop Syndrome

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

# Name GO ID Score Top Affiliating Genes
1 chromatin GO:0000785 8.92 PAX9 MSX1 DLX1 BARX1

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

# Name GO ID Score Top Affiliating Genes
1 regulation of transcription, DNA-templated GO:0006355 9.73 PAX9 MSX1 DLX1 BARX1
2 multicellular organism development GO:0007275 9.71 PAX9 MSX1 EDAR DLX1
3 anterior/posterior pattern specification GO:0009952 9.48 MSX1 BARX1
4 transforming growth factor beta receptor signaling pathway GO:0007179 9.46 LTBP3 LTBP2
5 anatomical structure development GO:0048856 9.37 PAX9 BARX1
6 odontogenesis GO:0042476 9.32 PAX9 MSX1
7 bone morphogenesis GO:0060349 9.26 MSX1 LTBP3
8 face morphogenesis GO:0060325 9.16 PAX9 MSX1
9 regulation of odontogenesis GO:0042481 8.96 PAX9 MSX1
10 odontogenesis of dentin-containing tooth GO:0042475 8.8 MSX1 EDAR DLX1

Molecular functions related to Witkop 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 9.46 PAX9 MSX1 DLX1 BARX1
2 sequence-specific double-stranded DNA binding GO:1990837 9.43 PAX9 MSX1 DLX1
3 growth factor binding GO:0019838 8.96 LTBP3 LTBP2
4 RNA polymerase II regulatory region sequence-specific DNA binding GO:0000977 8.92 PAX9 MSX1 DLX1 BARX1

Sources for Witkop Syndrome

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 20-May-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
Content
Loading form....