Rare Hematology News

Disease Profile

Tylosis with esophageal cancer

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
<1 / 1 000 000

< 331

US Estimated

< 514

Europe Estimated

Age of onset

Adolescent

ICD-10

-

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

rnn-autosomaldominant.svg

Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

no.svg

X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

no.svg

X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

no.svg

Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

no.svg

Not applicable

no.svg

Other names (AKA)

TOC; Keratosis palmoplantaris with esophageal cancer; Howel-Evans syndrome;

Categories

Congenital and Genetic Diseases; Digestive Diseases; Rare Cancers;

Summary

Tylosis with esophageal cancer (TOC)is an inherited condition that increases the risk for esophageal cancer. The symptoms of TOC include thickening of the skin on the palms and soles of the feet (palmoplantar keratoderma) and white lesions inside the mouth. People with TOC are at very high risk to develop esophageal cancer. The palmoplantar keratoderma usually occurs in childhood, and esophageal cancer usually occurs in adulthood. TOC is caused by a variant in the RHBDF2 gene and is inherited in an autosomal dominant pattern. Diagnosis is based on the symptoms, clinical exam, and family history. The diagnosis may be confirmed by the results of genetic testing. Treatment is focused on managing the risk for esophageal cancer through screening and avoiding smoking and alcohol use.[1][2][3][4]

Symptoms

The following list includes the most common signs and symptoms in people with tylosis with esophageal cancer. These features may be different from person to person. Some people may have more symptoms than others and the age at which symptoms occur may vary. This list does not include every symptom that has been described in the condition.

Symptoms of tylosis with esophageal cancer may include:[1][3] 

The skin findings usually begin in childhood. Esophageal cancer usually develops by mid-adulthood. The symptoms of esophageal cancer may include difficulty swallowing, loss of appetite, and weight loss.[2]

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Abnormal large intestine morphology
Abnormality of the large intestine
0002250
Esophageal neoplasm
Esophageal tumor
0100751
Gastrointestinal hemorrhage
Gastrointestinal bleeding
0002239
Nausea and vomiting
0002017
Palmoplantar keratoderma
Thickening of palms and soles
0000982
30%-79% of people have these symptoms
Abnormality of the mediastinum
0045026
Ascites
Accumulation of fluid in the abdomen
0001541
Dysphagia
Poor swallowing
Swallowing difficulties
Swallowing difficulty

[ more ]

0002015
Gastroesophageal reflux
Acid reflux
Acid reflux disease
Heartburn

[ more ]

0002020
Hepatomegaly
Enlarged liver
0002240
Poor appetite
Decreased appetite
0004396
Poor suck
Poor sucking
0002033
Weight loss
0001824
5%-29% of people have these symptoms
Clubbing of toes
0100760
Percent of people who have these symptoms is not available through HPO
Abnormality of the mouth
Abnormal mouth
0000153
Autosomal dominant inheritance
0000006
Diffuse palmoplantar hyperkeratosis
0007447
Esophageal carcinoma
0011459
Neoplasm
0002664
Parakeratosis
0001036

Cause

Tylosis with esophageal cancer occurs when the RHBDF2 gene is not working correctly. DNA changes known as pathogenic variants are responsible for making genes work incorrectly or sometimes, not at all.[1]

Diagnosis

Tylosis with esophageal cancer is diagnosed based on the symptoms, clinical exam, and family history. It may be confirmed by the results of genetic testing. A small piece of an esophageal lesion may be removed for examination under the microscope (biopsy) to help diagnose cancer. Imaging studies may also be helpful.[2][4]

Treatment

Treatment of tylosis with esophageal cancer is focused on early detection of esophageal cancer, as well as diet and lifestyle modifications. These modifications include quitting smoking and restricting alcohol use. The skin findings are treated with lotions and medications as necessary.[2][4]

Specialists involved in the care of someone with tylosis with esophageal cancer may include:

  • Dermatologist
  • Gastroenterologist
  • Oncologist

Learn more

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

In-Depth Information

  • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
  • PubMed is a searchable database of medical literature and lists journal articles that discuss Tylosis with esophageal cancer. Click on the link to view a sample search on this topic.

References

  1. Blaydon DC, Etheridge SL, Risk JM, Hennies HC, Gay LJ, et al. RHBDF2 mutations are associated with tylosis, a familial esophageal cancer syndrome. Am J Hum Genet. Feb 10, 2012; 90(2):340-6. https://pubmed.ncbi.nlm.nih.gov/22265016/.
  2. Ellis A, Risk JM, Maruthappu T, Kelsell DP. Tylosis with oesophageal cancer: Diagnosis, management and molecular mechanisms. Orphanet J Rare Dis. Sep 29, 2015; 10:126. https://pubmed.ncbi.nlm.nih.gov/26419362/.
  3. Jenkins LE, Abner S, Schadt C. A survey study with assessment of esophageal screening and genetic counseling in patients with Howel-Evans syndrome. Dermatol Online J. Jun 15, 2018; 24(6):13030/qt1c03j65k. https://pubmed.ncbi.nlm.nih.gov/30142717/.
  4. Ramai D, Lai JK, Ofori E, Linn S, Reddy M. Evaluation and Management of Premalignant Conditions of the Esophagus: A Systematic Survey of International Guidelines. J Clin Gastroenterol. Oct 2019; 53(9):627-634. https://pubmed.ncbi.nlm.nih.gov/31403982/.
  5. Qu L, Sha S, Zou QL, Gao XH, Xiao T, Chen HD, He CC. Whole Exome Sequencing Identified a Novel Mutation of the RHBDF2 Gene in a Chinese Family of Tylosis with Esophageal Cancer. Acta Derm Venereol. Jun 1, 2019; 99(7):699-700. https://pubmed.ncbi.nlm.nih.gov/30938830/.

Rare Hematology News