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Mini Review
Familial tylosis
Othman Saraj, Janusz A Jankowski
Digestive Disease Centre, University Hospitals of Leicester NHS Trust, Leicester, United Kingdom (OS,
JAJ); Gastrointestinal Cancer Presentation Group, Oxford University, Oxford, United Kingdom (JAJ); GI
Centre, Queen Mary's Hospital, University of London, London, United Kingdom (JAJ)
Published in Atlas Database: July 2009
Online updated version : http://AtlasGeneticsOncology.org/Kprones/FamTylosisID10100.html
DOI: 10.4267/2042/44788
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 2.0 France Licence.
© 2010 Atlas of Genetics and Cytogenetics in Oncology and Haematology
papules) on the body and flexure areas, are often seen
in patients with tylosis and it could be a possible
indication for developing oesophageal cancer (Tyldesly
and Osborne-Hughes, 1973; Tyldesly, 1974).
See example of Tylosis on DermAtlas.
Identity
Alias: Howell-Evans syndromes; Tylosis oesophageal
cancer; Focal non epidermolytic palmoplantar
keratoderma (NEPPK) with carcinoma of the
oesophagus
Note: Synonyms include: (a) Tylosis oesophageal
cancer or (b) Focal Non Epidermolytic Palmoplantar
Keratoderma (NEPPK) with carcinoma of the
oesophagus (Howel-Evans et al., 1958; Stevens et al.,
1996).
Inheritance: Is a rare autosomal dominant condition
with full penetrance of skin phenotype by puberty. No
race prevalence has been noted (Howel-Evans et al.,
1958).
Neoplastic risk
Malignancy Risk: Type A has a higher risk of
developing squamous oesophageal carcinoma up to
95% by age of 65 years, while Type B runs a benign
course (Howel-Evans et al., 1958; Ellis et al., 1994;
Stevens et al., 1996).
These malignancies are predominantly in the distal
esophagus whereas acquired squamous cell carcinomas
are mostly mid-thoracic in location (Howel-Evans et
al., 1958; Maillefer and Greydanus, 1999). Increase
risk has been noted with history of smoking (Stevens et
al., 1996).
Histological findings: Thickening of the all skin layers
especially epidermis, hypertrophy of sweat glands and
their ducts which often occluded by hyperplastic
epithelium (Howel-Evans et al., 1958).
Clinics
Phenotype and clinics
Tylosis is divided into to types: Type A with late onset
of NEPPK between age of 5 to 15 years and Type B
with early onset around the first year of age (Maillefer
and Greydanus, 1999; Nagai et al., 2000).
It usually involves the pressure areas mainly sole of
feet and later mild involvement of palms (more obvious
in manual workers). It can also affect frictional areas
like elbows and knees. It regresses completely on bed
rest (Howel-Evans et al., 1958; Stevens et al., 1996).
The affected skin has a thickened epidermis which
sheds horny large flakes, usually in autumn, to leave a
red tender surface which quickly get covered with
another thick layer of epidermis (Howel-Evans et al.,
1958).
Oral leukokeratosis (which are white "spongy" plaques)
and follicular hyperkeratosis (which are pinkish-to-tan
Atlas Genet Cytogenet Oncol Haematol. 2010; 14(6)
Treatment
Monitoring: Annual endoscopic surveillance with
biopsies taken should be offered to affected individuals
in view of risk of oesophageal cancer (Robertson et al.,
2008).
Prognosis
Prognosis of squamous cell cancer of oesophagus: In
general is poor with 5 year survival of 75% in Stage 0
(intraepithelial cancer) to <5% in stage IV (Distant
metastasis). Overall survival is about 20-25% (Mayer,
2001).
597
Familial tylosis
Saraj O, Jankowski JA
Ellis A, Field JK, Field EA, Friedmann PS, Fryer A, Howard P,
Leigh IM, Risk J, Shaw JM, Whittaker J. Tylosis associated
with carcinoma of the oesophagus and oral leukoplakia in a
large Liverpool family--a review of six generations. Eur J
Cancer B Oral Oncol. 1994;30B(2):102-12
Cytogenetics
Note
The tylosis oesophageal cancer gene (TOC) is localized
to a small region on band 17q25, a region frequently
deleted in persons with sporadic squamous cell
oesophageal tumours (Kelsell et al., 1996; Risk et al.,
2002).
This region contains 5'end of uncharacterized (FM8)
gene, which is likely non coding RNA, a promoter of
another gene and the whole cytoglobin gene (Langan et
al., 2004).
So far studies has failed to identify TOC specific
mutations in any of the 3 genes above (Langan et al.,
2004).
However recent studies of the gene expression in the
42.5 kb TOC minimal region has shown down
regulation of cytoglobin gene expression by 70% in
tylotic patients which might contribute to TOC
phenotype. This reduction exceeds the expected 50%
effect from autosomal dominant conditions therefore
rules out a simple haplo-insufficiency as a mechanism
of the disease, instead a novel trans-allele interaction
(ie the mutated allele causing suppression of the normal
allele) has been suggested (McRonald et al., 2006).
Kelsell DP, Risk JM, Leigh IM, Stevens HP, Ellis A, Hennies
HC, Reis A, Weissenbach J, Bishop DT, Spurr NK, Field JK.
Close mapping of the focal non-epidermolytic palmoplantar
keratoderma (PPK) locus associated with oesophageal cancer
(TOC). Hum Mol Genet. 1996 Jun;5(6):857-60
Stevens HP, Kelsell DP, Bryant SP, Bishop DT, Spurr NK,
Weissenbach J, Marger D, Marger RS, Leigh IM. Linkage of an
American pedigree with palmoplantar keratoderma and
malignancy (palmoplantar ectodermal dysplasia type III) to
17q24. Literature survey and proposed updated classification
of the keratodermas. Arch Dermatol. 1996 Jun;132(6):640-51
Maillefer RH, Greydanus MP. To B or not to B: is tylosis B truly
benign? Two North American genealogies. Am J
Gastroenterol. 1999 Mar;94(3):829-34
Nagai H, Emi M. [Palmoplantar keratosis]. Nippon Rinsho.
2000 Jul;58(7):1501-4
Harada H, Nagai H, Mine N, Terada Y, Fujiwara H, Mikami I,
Tsuneizumi M, Yabe A, Miyazaki K, Yokota T, Imoto I, Inazawa
J, Emi M. Molecular cloning, tissue expression, and
chromosomal assignment of a novel gene encoding a subunit
of the human signal-recognition particle. J Hum Genet.
2001;46(2):70-5
Mayer RJ.. Gastrointestinal tract cancer. Harrison's principles
of internal medicine, 15th Edition , volume 1, Chapter 90, 2001,
page 578-579.
Genes involved and proteins
Risk JM, Evans KE, Jones J, Langan JE, Rowbottom L,
McRonald FE, Mills HS, Ellis A, Shaw JM, Leigh IM, Kelsell
DP, Field JK. Characterization of a 500 kb region on 17q25
and the exclusion of candidate genes as the familial Tylosis
Oesophageal Cancer (TOC) locus. Oncogene. 2002 Sep
12;21(41):6395-402
TOC
Location
17q25
Note
TOC gene or tylosis with oesophageal cancer gene.
DNA/RNA
Note: Abnormality in this area has been noted in breast
and ovarian cancer (Nagai et al., 2000; Harada et al.,
2001).
Description: 42.5kb.
No mutations have been identified in the gene.
Langan JE, Cole CG, Huckle EJ, Byrne S, McRonald FE,
Rowbottom L, Ellis A, Shaw JM, Leigh IM, Kelsell DP, Dunham
I, Field JK, Risk JM. Novel microsatellite markers and single
nucleotide polymorphisms refine the tylosis with oesophageal
cancer (TOC) minimal region on 17q25 to 42.5 kb: sequencing
does not identify the causative gene. Hum Genet. 2004
May;114(6):534-40
McRonald FE, Liloglou T, Xinarianos G, Hill L, Rowbottom L,
Langan JE, Ellis A, Shaw JM, Field JK, Risk JM. Downregulation of the cytoglobin gene, located on 17q25, in tylosis
with oesophageal cancer (TOC): evidence for trans-allele
repression. Hum Mol Genet. 2006 Apr 15;15(8):1271-7
References
HOWEL-EVANS W, McCONNELL RB, CLARKE CA,
SHEPPARD PM. Carcinoma of the oesophagus with keratosis
palmaris et plantaris (tylosis): a study of two families. Q J Med.
1958 Jul;27(107):413-29
Robertson EV, Jankowski JA. Genetics of gastroesophageal
cancer: paradigms, paradoxes, and prognostic utility. Am J
Gastroenterol. 2008 Feb;103(2):443-9
Tyldesley WR, Hughes RO. Letter: Tylosis, leukoplakia, and
oesophageal carcinoma. Br Med J. 1973 Nov 17;4(5889):427
This article should be referenced as such:
Tyldesley WR. Oral leukoplakia associated with tylosis and
Saraj O, Jankowski JA. Familial tylosis. Atlas Genet Cytogenet
Oncol Haematol. 2010; 14(6):597-598.
esophageal carcinoma. J Oral Pathol. 1974;3(2):62-70
Atlas Genet Cytogenet Oncol Haematol. 2010; 14(6)
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