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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
Bakker MK, Bergman JEH, Krikov S, Amar E, Cocchi G, Cragan J, de Walle HEK, Gatt M, Groisman B, Liu S, Nembhard WN, Pierini A, Rissmann A, Chidambarathanu S, Sipek A Jr, Szabova E, Tagliabue G, Tucker D, Mastroiacovo P, Botto LD
BMJ Open 2019 Jul 2;9(7):e028139. doi: 10.1136/bmjopen-2018-028139. PMID: 31270117Free PMC Article

Recent clinical studies

Etiology

Andersen ND, Scherba JC, Turek JW
Curr Cardiol Rep 2020 Aug 8;22(10):115. doi: 10.1007/s11886-020-01363-5. PMID: 32770360
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
Tabbutt S, Tweddell JS, Ghanayem N
Pediatr Crit Care Med 2016 Aug;17(8 Suppl 1):S318-22. doi: 10.1097/PCC.0000000000000783. PMID: 27490617
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
Nand S, Godwin JE
Cancer 1988 Sep 1;62(5):958-64. doi: 10.1002/1097-0142(19880901)62:5<958::aid-cncr2820620519>3.0.co;2-p. PMID: 3409176

Diagnosis

Votavová H, Lenertová Z, Votava T, Beličková M
Klin Onkol 2023 Spring;36(3):206-214. doi: 10.48095/ccko2023206. PMID: 37353349
Pedra SRFF
World J Pediatr Congenit Heart Surg 2022 Sep;13(5):571-575. doi: 10.1177/21501351221115630. PMID: 36053109
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

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
Oh H
Circ Res 2017 Apr 14;120(8):1353-1366. doi: 10.1161/CIRCRESAHA.117.309697. PMID: 28408455
Santini V
Hematology Am Soc Hematol Educ Program 2016 Dec 2;2016(1):462-469. doi: 10.1182/asheducation-2016.1.462. PMID: 27913517Free PMC Article
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
Tabbutt S, Tweddell JS, Ghanayem N
Pediatr Crit Care Med 2016 Aug;17(8 Suppl 1):S318-22. doi: 10.1097/PCC.0000000000000783. PMID: 27490617

Prognosis

Schmiel M, Kido T, Georgiev S, Burri M, Heinisch PP, Vodiskar J, Strbad M, Ewert P, Hager A, Hörer J, Ono M
Interact Cardiovasc Thorac Surg 2022 Jul 9;35(2) doi: 10.1093/icvts/ivac190. PMID: 35876534Free PMC Article
Childs RW, Tian X, Vo P, Purev E, Kotecha RR, Carlsten M, Clara J, Flegel WA, Adams SD, Khuu HM, Stroncek DF, Cook L, Worthy T, Geller NL, Wells B, Wilder J, Reger R, Aue G
Br J Haematol 2021 Jun;193(5):951-960. Epub 2021 May 15 doi: 10.1111/bjh.17406. PMID: 33993466Free PMC Article
Bi WJ, Xiao YJ, Liu YJ, Hou Y, Ren WD
BMC Cardiovasc Disord 2021 Jan 6;21(1):15. doi: 10.1186/s12872-020-01837-y. PMID: 33407161Free PMC Article
Hamzah M, Othman HF, Elsamny E, Agarwal H, Aly H
Pediatr Cardiol 2020 Apr;41(4):781-788. Epub 2020 Feb 1 doi: 10.1007/s00246-020-02312-3. PMID: 32008059
Bailey LL, Gundry SR
Pediatr Clin North Am 1990 Feb;37(1):137-50. doi: 10.1016/s0031-3955(16)36836-5. PMID: 1689814

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
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
Santini V
Hematology Am Soc Hematol Educ Program 2016 Dec 2;2016(1):462-469. doi: 10.1182/asheducation-2016.1.462. PMID: 27913517Free 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
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

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
Hansen T, Henriksen TB, Bach CC, Matthiesen NB
Pediatr Neurol 2017 Jul;72:7-18.e1. Epub 2017 Apr 1 doi: 10.1016/j.pediatrneurol.2017.03.014. PMID: 28549654
Agarwal A, Firdouse M, Brar N, Yang A, Lambiris P, Chan AK, Mondal TK
Clin Appl Thromb Hemost 2017 Nov;23(8):911-921. Epub 2016 Nov 22 doi: 10.1177/1076029616679506. PMID: 27879470
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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