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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: pubs@smfm.org, 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

Datta S, Cao W, Skillman M, Wu M
Int J Mol Sci 2023 Oct 17;24(20) doi: 10.3390/ijms242015249. PMID: 37894928Free PMC Article
Votavova H, Belickova M
Int J Oncol 2022 Jan;60(1) Epub 2021 Dec 27 doi: 10.3892/ijo.2021.5297. PMID: 34958107Free PMC Article
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
Roeleveld PP, Axelrod DM, Klugman D, Jones MB, Chanani NK, Rossano JW, Costello JM
Cardiol Young 2018 Nov;28(11):1275-1288. Epub 2018 Sep 18 doi: 10.1017/S104795111800135X. PMID: 30223915
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

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
Vanlerberghe C, Boutry N, Petit F
Clin Genet 2018 Jul;94(1):43-53. Epub 2018 Apr 11 doi: 10.1111/cge.13209. PMID: 29322497
Pula JH, Mehta M
Curr Opin Ophthalmol 2014 Nov;25(6):480-4. doi: 10.1097/ICU.0000000000000106. PMID: 25237931
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
Bagby GC, Lipton JM, Sloand EM, Schiffer CA
Hematology Am Soc Hematol Educ Program 2004:318-36. doi: 10.1182/asheducation-2004.1.318. PMID: 15561690

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
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
Ohye RG, Schranz D, D'Udekem Y
Circulation 2016 Oct 25;134(17):1265-1279. doi: 10.1161/CIRCULATIONAHA.116.022816. PMID: 27777296Free PMC Article
Barron DJ, Kilby MD, Davies B, Wright JG, Jones TJ, Brawn WJ
Lancet 2009 Aug 15;374(9689):551-64. doi: 10.1016/S0140-6736(09)60563-8. PMID: 19683641
Sloand EM
Hematol Oncol Clin North Am 2009 Apr;23(2):347-60. doi: 10.1016/j.hoc.2009.01.015. PMID: 19327588

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
Loh AYT, Špoljar S, Neo GYW, Escande-Beillard N, Leushacke M, Luijten MNH, Venkatesh B, Bonnard C, van Steensel MAM, Hamm H, Carmichael A, Rajan N, Carney TJ, Reversade B
Am J Med Genet A 2022 Jun;188(6):1752-1760. Epub 2022 Feb 25 doi: 10.1002/ajmg.a.62703. PMID: 35212137
Roeleveld PP, Axelrod DM, Klugman D, Jones MB, Chanani NK, Rossano JW, Costello JM
Cardiol Young 2018 Nov;28(11):1275-1288. Epub 2018 Sep 18 doi: 10.1017/S104795111800135X. PMID: 30223915
Pabuşçu Y, Bulakbasi N, Kocaoğlu M, Uçöz T
Comput Med Imaging Graph 2002 Nov-Dec;26(6):453-8. doi: 10.1016/s0895-6111(02)00026-5. PMID: 12453509
Norwood WI
Cardiol Clin 1989 May;7(2):377-85. PMID: 2659180

Clinical prediction guides

Votavová H, Lenertová Z, Votava T, Beličková M
Klin Onkol 2023 Spring;36(3):206-214. doi: 10.48095/ccko2023206. PMID: 37353349
Bono E, McLornan D, Travaglino E, Gandhi S, Gallì A, Khan AA, Kulasekararaj AG, Boveri E, Raj K, Elena C, Ireland RM, Bianchessi A, Jiang J, Todisco G, Ferretti VV, Cazzola M, Marsh JCW, Malcovati L, Mufti GJ
Leukemia 2019 Oct;33(10):2495-2505. Epub 2019 Apr 2 doi: 10.1038/s41375-019-0457-1. PMID: 30940907
Vanlerberghe C, Boutry N, Petit F
Clin Genet 2018 Jul;94(1):43-53. Epub 2018 Apr 11 doi: 10.1111/cge.13209. PMID: 29322497
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
Smith AT, Sack GH Jr, Taylor GJ
J Pediatr 1979 Oct;95(4):538-43. doi: 10.1016/s0022-3476(79)80758-1. PMID: 480027

Recent systematic reviews

Mendel B, Kohar K, Amirah S, Vidya AP, Utama KE, Prakoso R, Siagian SN
Int J Cardiol 2023 Jul 1;382:106-111. Epub 2023 Mar 29 doi: 10.1016/j.ijcard.2023.03.050. PMID: 36996909
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
Goldberg O, Moretti M, Levy A, Koren G
J Obstet Gynaecol Can 2015 Feb;37(2):150-156. doi: 10.1016/S1701-2163(15)30337-6. PMID: 25767948
Khalil A, Suff N, Thilaganathan B, Hurrell A, Cooper D, Carvalho JS
Ultrasound Obstet Gynecol 2014 Jan;43(1):14-24. Epub 2013 Dec 10 doi: 10.1002/uog.12526. PMID: 23737029

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