Commonly referred to as “Tylosis”
Facts
- What does the RHBDF2 gene do? encodes a protein belonging to the rhomboid family intramembrane serine proteases.2
- What happens when RHBDF2 becomes mutated? Mutated protein leads to higher secretion of a ligand, amphiregulin, for the epidermal growth factor receptor family.1
- Clinical significance of mutation? Palmoplantar keratoderma and oral leukokeratosis in some cases.3
About Tylosis
Skin disease caused by RHBDF2 mutations is known as Tylosis.1 The disease is caused by a gain of function mutation of the inactive rhomboid protease, which leads to hyperproliferative skin disease.1,2 This type of mutation typically allows the altered gene to possess a new molecular function. Tylosis is very rare and is passed down from a parent to their offspring in an autosomal dominant inheritance pattern.2 This means that it only takes one copy of the mutated RHBDF2 gene from one parent to cause Tylosis. The parent who has Tylosis has a 50% chance of passing the mutated RHBDF2 gene in each pregnancy. Genetic testing is necessary to determine whether or not symptoms of Tylosis are caused by a mutation in the RHBDF2 gene.3
Symptoms of RHBDF2
Signs of Tylosis usually appear by 7 or 8 years of age but can start as late as puberty.3 Hyperkeratotic lesions start to appear on the palms of the hands as well as the soles of the feet. The keratoderma appears as yellowish thickening of the outer layer of skin.2 This occurs on weight-bearing areas of the palms and soles that are subject to friction.3 In addition to hyperkeratosis of palms and soles, oral leukoplakia is also typically present in patients with Tylosis. This appears as white patches or spots inside the mouth. It is important to note that Tylosis is also characterized by a high risk of esophageal cancer.2 Tylosis-associated squamous cell esophageal usually appears in the mid-fifties and later. Studies are being done to explore the safety benefit of regular endoscopic screening for patients with Tylosis.3
IPCRR Data for RHBDF2
Two individuals fully enrolled in the International Pachyonychia Congenita Research Registry (IPCRR) were found not to have PC but instead carry a mutation in RHBDF2 gene. One is in the United States, and one is in England. Both individuals reported thickening of the toenails and/or fingernails. Both stated plantar keratosis that is painful and always present. Both reported constant palmar keratosis, however, only one of them reported pain associated with it. One of them reported oral leukokeratosis.
References
- Hosur V, Lyons BL, Burzenski LM, Shultz LD. Tissue-specific role of RHBDF2 in cutaneous wound healing and hyperproliferative skin disease. BMC Res Notes. 2017;10(1):573. Published 2017 Nov 7. doi:10.1186/s13104-017-2899-8
- Qu L, Sha S, Zou QL, et al. Whole Exome Sequencing Identified a Novel Mutation of the RHBDF2 Gene in a Chinese Family of Tylosis with Esophageal Cancer. Acta Derm Venereol. 2019;99(7):699-700. doi:10.2340/00015555-3189
- Ellis A, Risk JM, Maruthappu T, Kelsell DP. Tylosis with oesophageal cancer: Diagnosis, management and molecular mechanisms. Orphanet J Rare Dis. 2015;10:126. Published 2015 Sep 29. doi:10.1186/s13023-015-0346-2
*International Pachyonychia Congenita Research Registry (IPCRR) is a WCG IRB approved study #1057496 IRB #20040468 sponsored by Pachyonychia Congenita Project a 501(c)3 public charity. Visit www.pachyonychia.org for additional information.
