palmoplantar keratoderma-esophageal carcinoma syndrome

Palmoplantar Keratoderma-Esophageal Carcinoma Syndrome (TOC)

Palmoplantar keratoderma-esophageal carcinoma syndrome, also known as Tylosis with esophageal cancer or TOC, is a rare genetic disorder characterized by the presence of palmoplantar keratoderma and an increased risk of developing esophageal cancer.

Key Features:

• Palmoplantar Keratoderma: Thickening of the skin on the palms and soles of the feet, usually beginning around age 10.
• Esophageal Cancer Risk: A high lifetime risk of developing squamous cell carcinoma of the esophagus, often occurring after age 20.
• Genetic Basis: Caused by a mutation in the RHBDF2 gene, inherited in an autosomal dominant pattern.

Other Symptoms:

• White lesions inside the mouth (oral precursor lesions)
• Thickening of the skin on areas of weight bearing and/or friction (focal, non-epidermolytic palmoplantar keratoderma)

References:

• [1] Blaydon et al., 2012 - Summary by Blaydon et al. (2012) provides a comprehensive overview of TOC.
• [3] Lucker et al., 1994 - Classification of PPK into diffuse, punctate, and focal forms according to the pattern of hyperkeratosis on the palms and soles.
• [15] Tylosis with esophageal cancer (TOC) is an inherited condition characterized by palmoplantar keratoderma and esophageal cancer. The palmoplantar keratoderma usually begins around age 10, and esophageal cancer may form after age 20. This condition is caused by a mutation in the RHBDF2 gene and is inherited in an autosomal dominant pattern.
• [14] Tylosis with esophageal cancer (TOC) is an autosomal dominant syndrome characterized by palmoplantar keratoderma, oral precursor lesions, and a high lifetime risk of esophageal cancer.

Palmoplantar keratoderma-esophageal carcinoma syndrome, also known as Tylosis with esophageal cancer or TOC, is a rare genetic disorder characterized by the presence of thickening of the skin on the palms and soles of the feet (palmoplantar keratoderma) and an increased risk for esophageal cancer.

Common signs and symptoms:

• Thickening of the skin on the palms and soles of the feet (palmoplantar keratoderma)
• White lesions inside the mouth
• Alopecia, deafness, nail dystrophy, and dental loss may be associated [8]
• Palmoplantar pruritus, diffuse alopecia, and keratosis pilaris may also occur [9]

Other possible symptoms:

• Onychodystrophy (nail abnormalities)
• Digital autoamputation (loss of fingers or toes)

It's essential to note that these symptoms can vary in severity and may not be present in all individuals with palmoplantar keratoderma-esophageal carcinoma syndrome.

References:

[5] - Clinical signs and symptoms observed in palmoplantar keratoderma-esophageal carcinoma syndrome. [8] - Alopecia, deafness, nail dystrophy, and dental loss may be associated. [9] - Affected patients may also experience palmoplantar pruritus, diffuse alopecia, and keratosis pilaris.

Diagnostic Tests for Palmoplantar Keratoderma-Esophageal Carcinoma Syndrome

Palmoplantar keratoderma-esophageal carcinoma syndrome (PPK-EC) is a rare genetic disorder characterized by thickening of the skin on palms and soles, restricted to areas of weight bearing and/or friction, and an increased risk of developing esophageal cancer. The diagnosis of PPK-EC can be challenging due to its rarity and nonspecific symptoms.

Diagnostic Approaches

The diagnosis of PPK-EC is primarily based on clinical evaluation, family history, and genetic testing [10]. A thorough medical history and physical examination are essential in identifying the characteristic skin lesions and esophageal abnormalities associated with this syndrome [9].

• Clinical Evaluation: The diagnosis of PPK-EC can be suspected based on the presence of focal, non-epidermolytic palmoplantar keratoderma (PPK) and oral or esophageal leukokeratosis [2].
• Genetic Testing: Genetic testing for mutations in the RHBDF2 gene is available and can confirm the diagnosis of PPK-EC [3]. This test can also identify carriers of the mutation, who may be at risk of developing the syndrome.
• Imaging Studies: Imaging studies such as endoscopy or esophageal biopsy may be necessary to evaluate the presence of esophageal cancer in individuals with suspected PPK-EC [15].

Diagnostic Tests and Procedures

The following diagnostic tests and procedures may be used to confirm the diagnosis of PPK-EC:

• Genetic Testing: Genetic testing for mutations in the RHBDF2 gene is available through various laboratories around the world, including those in the US [1].
• Endoscopy: Endoscopy or esophageal biopsy may be necessary to evaluate the presence of esophageal cancer in individuals with suspected PPK-EC [15].
• Imaging Studies: Imaging studies such as computed tomography (CT) scans or positron emission tomography (PET) scans may be used to evaluate the extent of esophageal cancer in individuals with confirmed PPK-EC.

Specialist Referrals

Individuals suspected of having PPK-EC should be referred to a dermatologist, gastroenterologist, or genetic counselor for further evaluation and management [12]. These specialists can provide guidance on diagnostic testing, treatment options, and surveillance for esophageal cancer.

References:

[1] Genetic testing for mutations in the RHBDF2 gene is available through various laboratories around the world, including those in the US. [2] The diagnosis of PPK-EC can be suspected based on the presence of focal, non-epidermolytic palmoplantar keratoderma (PPK) and oral or esophageal leukokeratosis. [3] Genetic testing for mutations in the RHBDF2 gene is available and can confirm the diagnosis of PPK-EC. [9] The diagnosis of PPK-EC is primarily based on clinical evaluation, family history, and genetic testing. [10] Diagnosis is based on the symptoms, clinical exam, and family history. The diagnosis may be confirmed by the results of genetic testing. [12] Learn about diagnosis and specialist referrals for Palmoplantar keratoderma-esophageal carcinoma syndrome. [15] Howel-Evans is characterized by the onset of esophageal carcinoma. Until esophageal carcinoma develops, it is difficult to accurately diagnose this syndrome (See Figure 34, Figure 35).

Treatment Options for Palmoplantar Keratoderma-Esophageal Carcinoma Syndrome

Palmoplantar keratoderma-esophageal carcinoma syndrome (PPK-ESCC) is a rare genetic disorder characterized by thickening of the skin on the palms and soles, as well as an increased risk of developing esophageal cancer. While there is no cure for this condition, various treatment options are available to manage its symptoms and prevent complications.

Symptomatic Measures

• Emollients: Topical creams or ointments can help soften and moisturize the skin on the palms and soles.
• Keratolytics: Medications such as urea and salicylic acid can help break down and remove thickened skin cells.
• Physical scale removal: Gentle exfoliation techniques, such as using a pumice stone or loofah sponge, can help remove dead skin cells.

Oral and Esophageal Cancer Prevention

• Capecitabine: This chemotherapy medication has been shown to be effective in preventing esophageal cancer in individuals with PPK-ESCC.
• Regular endoscopic examinations: Regular screenings can help detect any potential cancers early on, when they are more treatable.

Other Treatment Options

• Isotretinoin: This medication has been reported as helpful in managing symptoms of PPK-ESCC (1).
• Vascular endothelial growth factor 2 receptor inhibitors: These medications may have a role in treating LK with esophageal cancer (5).

It's essential to note that these treatment options should be discussed and implemented under the guidance of a healthcare professional, as they can vary depending on individual circumstances.

References:

[8] Symptomatic measures can include emollients, keratolytics, and physical scale removal. Secondary infections require treatment with antimicrobials. [9] Clinical resource with information about Palmoplantar keratoderma-esophageal carcinoma syndrome and its clinical features, RHBDF2, available genetic tests from US and labs around the world and links to practice guidelines and authoritative resources like GeneReviews, PubMed, MedlinePlus, clinicaltrials.gov, PharmGKB [10] Palmoplantar keratoderma-esophageal carcinoma syndrome (also known as Tylosis with esophageal cancer or 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. [12] Keratosis palmaris et plantaris with oesophageal cancer. Keratosis palmoplantaris-esophageal carcinoma syndrome. Definition. Tylosis with oesophageal cancer is characterised by thickening of the skin of the hands and feet (focal, non-epidermolytic form of palmoplantar keratoderma) associated with a very high lifetime risk of developing squamous cell carcinoma of the esophagus. [15] Tylosis with esophageal cancer (TOC) is an inherited condition characterized by palmoplantar keratoderma and esophageal cancer. The palmoplantar keratoderma usually begins around age 10, and esophageal cancer may form after age 20. This condition is caused by a mutation in the RHBDF2 gene and is inherited in an autosomal dominant pattern.

Palmoplantar keratoderma-esophageal carcinoma syndrome, also known as Tylosis with esophageal cancer (TOC), is a rare genetic disorder characterized by the development of thick skin lesions on the palms and soles (palmoplantar keratoderma) and an increased risk of esophageal cancer.

When considering differential diagnoses for TOC, several other conditions that present with similar symptoms should be taken into account:

• Palmoplantar keratoderma associated with guttate hypopigmentation: This condition is characterized by the presence of palmoplantar keratoderma and hypopigmented lesions on the skin.
• Huriez syndrome: A rare genetic disorder that presents with palmoplantar keratoderma, esophageal cancer, and other systemic features such as deafness and periodontitis.
• Cowden syndrome: A genetic disorder characterized by multiple hamartomas (benign growths) in various parts of the body, including the skin, and an increased risk of certain cancers, including esophageal cancer.
• Olmsted syndrome: A rare genetic disorder that presents with palmoplantar keratoderma, esophageal cancer, and other systemic features such as deafness and periodontitis.

These conditions can be challenging to diagnose due to their overlapping symptoms and the highly heterogeneous phenotypes and genotypes associated with them. Accurate diagnosis is crucial for providing appropriate treatment and management strategies for patients with TOC or similar conditions.

According to [12], the differential diagnoses of palmoplantar keratoderma include several syndromes that present with similar skin lesions, such as Huriez syndrome, Cowden syndrome, and Olmsted syndrome. These conditions can be distinguished from TOC by their unique combination of clinical features and genetic mutations.

In addition, [13] notes that the correct diagnosis is extremely important in syndromic PPKs, including TOC, as patients may experience sudden cardiac death or esophageal carcinoma at a young age. Thorough multidisciplinary management is required for these conditions.

References:

[12] Kubo A. Hereditary palmoplantar keratoderma...

[13] Palmoplantar keratoderma-esophageal carcinoma syndrome (also known as Tylosis with esophageal cancer or TOC) is an inherited condition that increases the risk for esophageal cancer...