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Hypoplastic enamel-onycholysis-hypohidrosis syndrome(TNS)

MedGen UID:
140809
Concept ID:
C0406735
Disease or Syndrome
Synonyms: Dysplasia of nails with hypodontia; ECTODERMAL DYSPLASIA 3, TOOTH/NAIL TYPE; ECTODERMAL DYSPLASIA 3, WITKOP TYPE; NAIL DYSPLASIA WITH HYPODONTIA; TNS; Tooth-and-Nail Syndrome; WITKOP SYNDROME
SNOMED CT: Hypoplastic enamel-onycholysis-hypohidrosis syndrome (400036004); Witkop-Brearley-Gentry syndrome (400036004)
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
 
Gene (location): MSX1 (4p16.2)
 
Monarch Initiative: MONDO:0008582
OMIM®: 189500
Orphanet: ORPHA2228

Definition

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). [from OMIM]

Clinical features

From HPO
Agenesis of permanent teeth
MedGen UID:
224851
Concept ID:
C1290511
Congenital Abnormality
A congenital defect characterized by the absence of one or more permanent teeth, including oligodontia, hypodontia, and adontia of the of permanent teeth.
Microdontia of primary teeth
MedGen UID:
343501
Concept ID:
C1856203
Finding
Decreased size of the primary teeth.
Nail pits
MedGen UID:
57463
Concept ID:
C0150993
Finding
Small (typically about 1 mm or less in size) depressions on the dorsal nail surface.
Concave nail
MedGen UID:
66369
Concept ID:
C0221261
Finding
The natural longitudinal (posterodistal) convex arch is not present or is inverted.
Abnormal sweat gland morphology
MedGen UID:
892310
Concept ID:
C0262643
Anatomical Abnormality
Any structural abnormality of the sweat gland.
Ridged nail
MedGen UID:
140853
Concept ID:
C0423820
Finding
Longitudinal, linear prominences in the nail plate.
Fine hair
MedGen UID:
98401
Concept ID:
C0423867
Finding
Hair that is fine or thin to the touch.
Hypoplastic fifth toenail
MedGen UID:
868713
Concept ID:
C4023116
Anatomical Abnormality
Underdeveloped nails of the fifth toes.
Sparse hair
MedGen UID:
1790211
Concept ID:
C5551005
Finding
Reduced density of hairs.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVHypoplastic enamel-onycholysis-hypohidrosis syndrome

Professional guidelines

PubMed

Kulasekararaj A, Cavenagh J, Dokal I, Foukaneli T, Gandhi S, Garg M, Griffin M, Hillmen P, Ireland R, Killick S, Mansour S, Mufti G, Potter V, Snowden J, Stanworth S, Zuha R, Marsh J; BSH Committee
Br J Haematol 2024 Mar;204(3):784-804. Epub 2024 Jan 21 doi: 10.1111/bjh.19236. PMID: 38247114
Hellström-Lindberg ES, Kröger N
Blood 2023 Dec 28;142(26):2268-2281. doi: 10.1182/blood.2023020079. PMID: 37874917
Society for Maternal-Fetal Medicine (SMFM). Electronic address: [email protected], Prabhu M, Kuller JA, Biggio JR
Am J Obstet Gynecol 2021 Oct;225(4):B2-B15. Epub 2021 Jun 23 doi: 10.1016/j.ajog.2021.06.079. PMID: 34171388

Recent clinical studies

Etiology

Geoffrion TR, Fuller SM
World J Pediatr Congenit Heart Surg 2022 Sep;13(5):593-599. doi: 10.1177/21501351221111390. PMID: 36053102
Akintürk H, Yörüker U, Schranz D
World J Pediatr Congenit Heart Surg 2022 Sep;13(5):588-592. doi: 10.1177/21501351221099935. PMID: 36053094
Tanaka TN, Bejar R
Blood 2019 Mar 7;133(10):1086-1095. Epub 2019 Jan 22 doi: 10.1182/blood-2018-10-844670. PMID: 30670443
Yabrodi M, Mastropietro CW
Pediatr Res 2017 Jan;81(1-2):142-149. Epub 2016 Oct 4 doi: 10.1038/pr.2016.194. PMID: 27701379Free PMC Article
Crawford PJ, Aldred M, Bloch-Zupan A
Orphanet J Rare Dis 2007 Apr 4;2:17. doi: 10.1186/1750-1172-2-17. PMID: 17408482Free PMC Article

Diagnosis

de Blaauw I, Stenström P, Yamataka A, Miyake Y, Reutter H, Midrio P, Wood R, Grano C, Pakarinen M
Nat Rev Dis Primers 2024 Nov 21;10(1):88. doi: 10.1038/s41572-024-00574-2. PMID: 39572572
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Clin Genet 2023 Nov;104(5):528-541. Epub 2023 Jul 17 doi: 10.1111/cge.14404. PMID: 37455656
Tanaka TN, Bejar R
Blood 2019 Mar 7;133(10):1086-1095. Epub 2019 Jan 22 doi: 10.1182/blood-2018-10-844670. PMID: 30670443
Subramanian S, Gamanagatti S, Sinha A, Sampangi R
Indian Pediatr 2007 Dec;44(12):931-3. PMID: 18175850
Crawford PJ, Aldred M, Bloch-Zupan A
Orphanet J Rare Dis 2007 Apr 4;2:17. doi: 10.1186/1750-1172-2-17. PMID: 17408482Free PMC Article

Therapy

Friedman KG, Tworetzky W
Arch Cardiovasc Dis 2020 Feb;113(2):121-128. Epub 2020 Feb 26 doi: 10.1016/j.acvd.2019.06.007. PMID: 32113817
Rudolph AM
Pediatr Res 2020 Mar;87(4):630-633. Epub 2019 Oct 10 doi: 10.1038/s41390-019-0604-4. PMID: 31600768
Tanaka TN, Bejar R
Blood 2019 Mar 7;133(10):1086-1095. Epub 2019 Jan 22 doi: 10.1182/blood-2018-10-844670. PMID: 30670443
Patel NM, Birla RK
ASAIO J 2018 Jan/Feb;64(1):56-62. doi: 10.1097/MAT.0000000000000642. PMID: 28863042
Brenner JI, Kuehl K
Cardiol Young 2011 Dec;21 Suppl 2:23-7. doi: 10.1017/S1047951111001399. PMID: 22152525

Prognosis

Lopez KN, Morris SA, Krishnan A, Jacobs MB, Bhat AH, Chelliah A, Chiu JS, Cuneo BF, Freire G, Hornberger LK, Howley L, Husain N, Ikemba C, Kavanaugh-McHugh A, Kutty S, Lee C, McBrien A, Michelfelder EC, Pinto NM, Schwartz R, Stern KWD, Taylor C, Thakur V, Tworetzky W, Wittlieb-Weber C, Woldu K, Donofrio MT, Peyvandi S; Fetal Heart Society Research Collaborative
Circulation 2023 Jul 18;148(3):283-285. Epub 2023 Jul 17 doi: 10.1161/CIRCULATIONAHA.123.064476. PMID: 37459407Free PMC Article
Langley SM, Sunstrom RE, Reed RD, Rekito AJ, Gerrah R
Semin Thorac Cardiovasc Surg Pediatr Card Surg Annu 2013;16(1):43-51. doi: 10.1053/j.pcsu.2013.01.008. PMID: 23561817
Riyaz A, Riyaz N, Jayakrishnan MP, Mohamed Shiras PT, Ajith Kumar VT, Ajith BS
Indian J Pediatr 2007 Sep;74(9):862-3. doi: 10.1007/s12098-007-0155-2. PMID: 17901676
Bailey LL, Gundry SR
Pediatr Clin North Am 1990 Feb;37(1):137-50. doi: 10.1016/s0031-3955(16)36836-5. PMID: 1689814
Norwood WI
Cardiol Clin 1989 May;7(2):377-85. PMID: 2659180

Clinical prediction guides

Albrahimi E, Korun O
Eur J Cardiothorac Surg 2024 Jul 1;66(1) doi: 10.1093/ejcts/ezae247. PMID: 38913849
Matsuoka R, Muneuchi J, Ochiai Y
Cardiol Young 2021 Nov;31(11):1861-1863. Epub 2021 May 4 doi: 10.1017/S1047951121001670. PMID: 33941300
Evans WN, Galindo A, Rothman A, Ciccolo ML, Carrillo SA, Acherman RJ, Mayman GA, Cass KA, Kip KT, Luna CF, Ludwick JM, Rollins RC, Castillo WJ, Alexander JA, Restrepo H
Pediatr Cardiol 2016 Jun;37(5):868-77. Epub 2016 Mar 1 doi: 10.1007/s00246-016-1361-3. PMID: 26932364
Divanović A, Hor K, Cnota J, Hirsch R, Kinsel-Ziter M, Michelfelder E
J Thorac Cardiovasc Surg 2011 Apr;141(4):988-94. Epub 2010 Dec 3 doi: 10.1016/j.jtcvs.2010.09.043. PMID: 21130471
Crawford PJ, Aldred M, Bloch-Zupan A
Orphanet J Rare Dis 2007 Apr 4;2:17. doi: 10.1186/1750-1172-2-17. PMID: 17408482Free PMC Article

Recent systematic reviews

Derridj N, Calderon J, Bonnet D, Khoshnood B, Monier I, Guedj R
Eur J Pediatr 2024 May;183(5):1967-1987. Epub 2024 Feb 14 doi: 10.1007/s00431-023-05419-w. PMID: 38353800
Kim AY, Woo W, Saxena A, Tanidir IC, Yao A, Kurniawati Y, Thakur V, Shin YR, Shin JI, Jung JW, Barron DJ; International HLHS research network collaborators
Cardiol Young 2024 Mar;34(3):659-666. Epub 2023 Sep 19 doi: 10.1017/S1047951123002986. PMID: 37724575
Arif H, Ashraf R, Khan F, Khattak YR, Nisar H, Ahmad I
Orthod Craniofac Res 2024 Feb;27(1):15-26. Epub 2023 Aug 2 doi: 10.1111/ocr.12695. PMID: 37533308
Sandhu K, Pepe S, Smolich JJ, Cheung MMH, Mynard JP
Heart Lung Circ 2021 Nov;30(11):1602-1612. Epub 2021 Aug 20 doi: 10.1016/j.hlc.2021.07.018. PMID: 34420886
Liu Y, Chen S, Zühlke L, Black GC, Choy MK, Li N, Keavney BD
Int J Epidemiol 2019 Apr 1;48(2):455-463. doi: 10.1093/ije/dyz009. PMID: 30783674Free PMC Article

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