Familial tylosis

Howell-Evans syndromes , Tylosis oesophageal cancer , Focal non epidermolytic palmoplantar keratoderma (NEPPK) with carcinoma of the oesophagus

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).

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).

C538682

148500 , 148600

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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 affects 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 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.

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).

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 of squamous cell cancer of oesophagus: In general is poor with 5 year survival of 75% in Stage 0 (intraepithelial cancer) to

The tylosis oesophageal cancer gene (RHBDF2) 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 5end 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 RHBDF2 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 RHBDF minimal region has shown down regulation of cytoglobin gene expression by 70% in tylotic patients which might contribute to RHBDF2 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).

TOCTECTOCG

RHBDF2 gene or tylosis with oesophageal cancer gene.

42.5kb.
No mutations have been identified in the gene.