KRT1-related nonepidermolytic palmoplantar keratoderma

KRT1-related diffuse nonepidermolytic keratoderma (NEPPK) is a rare genetic disorder characterized by the thickening of skin on the palms and soles.

• The condition is caused by a heterozygous mutation in the KRT1 gene, which codes for one of the proteins that make up the skin's outer layer [1].
• Symptoms include well-demarcated hyperkeratosis (thickening of the skin) on the palms and soles, with a red band often present at the periphery [4].
• The condition is typically inherited in an autosomal dominant pattern, meaning that a single copy of the mutated gene is enough to cause the disorder [9].
• It's worth noting that there are different forms of NEPPK, including a focal form caused by mutations in the KRT16 gene [2].

Overall, KRT1-related diffuse nonepidermolytic keratoderma is a rare and relatively mild condition compared to other types of palmoplantar keratoderma.

Signs and Symptoms of KRT1-related Nonepidermolytic Palmoplantar Keratoderma

KRT1-related nonepidermolytic palmoplantar keratoderma is a genetic disorder characterized by the thickening of skin on the palms and soles. The signs and symptoms of this condition include:

• Diffuse thickening and fissuring of the palmar skin: This is a common feature of KRT1-related nonepidermolytic palmoplantar keratoderma, where the skin on the palms becomes thickened and develops fissures (cracks) [7].
• Plantar hyperkeratosis: The soles of the feet also show signs of thickening and hyperkeratosis, which is a condition characterized by an excessive growth of skin cells leading to thickening of the skin [7].
• Red band at the edges of keratosis: A red band or border is often seen around the areas of thickened skin on the palms and soles [3].
• Chronic periodontal disease: Individuals with KRT1-related nonepidermolytic palmoplantar keratoderma may also experience chronic periodontal disease, which can lead to early loss of teeth [4].
• Bilateral cataracts and optic nerve colobomata: Some individuals may also develop bilateral cataracts (clouding of the lens in both eyes) and optic nerve colobomata (a rare congenital defect of the eye) [4].

These signs and symptoms can vary in severity and may be accompanied by other features such as nail dystrophy, milia, and hyper- and/or hypopigmentation. It is essential to consult a medical professional for an accurate diagnosis and treatment plan.

References: [3] - What are the Signs & Symptoms? [4] - Variable features include chronic periodontal disease with early loss of teeth, bilateral cataracts and optic nerve colobomata, and hypertriglyceridemia. Naxos ... [7] - Clinical and pathological features. A, Diffuse thickening and fissuring of the palmar skin and volar surface of the fingers. B, Plantar ...

Based on the search results, it appears that diagnostic tests for KRT1-related nonepidermolytic palmoplantar keratoderma are available.

Available Diagnostic Tests:

• Genetic testing for mutations in the KRT1 gene is a possible diagnostic test for this condition [3].
• A biopsy of affected skin can also be used to diagnose KRT1-related nonepidermolytic palmoplantar keratoderma, as it will often show epidermolytic hyperkeratosis similar to that seen in epidermolytic ichthyosis [6].

Clinical Significance:

• The KRT1 gene is associated with a range of other genetically and phenotypically related disorders, including arrhythmogenic right ventricular dysplasia and Naxos disease [2].
• Genetic testing for the KRT1 gene can provide information on the clinical significance of mutations in this gene.

References:

• The test covers known genetic causes of PPK types/subtypes and a range of other genetically/phenotypically related disorders, depending on the gene involved [4].
• A biopsy sections will often show epidermolytic hyperkeratosis, similar to that seen in epidermolytic ichthyosis, although more than one sample may be required to confirm the diagnosis [6].

Note: The above information is based on search results 3 and 6.

Based on the search results, it appears that there are various treatment options available for KRT1-related non-epidermolytic palmoplantar keratoderma.

Topical Treatments

• Topical anti-inflammatories can be helpful for hyperkeratosis and itching [1].
• Emollients, keratolytic agents (such as 6% salicylic acid), topical retinoids, and steroids are used to treat palmoplantar keratoderma [9].

Oral Retinoids

• Oral retinoids can be helpful in decreasing the keratoderma and the intense associated discomfort [6][6].
• Low dose acitretin can help in some cases of palmoplantar keratoderma [10].

Other Treatments

• Topical medication (emollients, keratolytics, retinoids, steroids) and systemic retinoids are used, but only case series are available, and prospective studies are needed to confirm their effectiveness [7].
• Treatment with etretinate for several months led to partial improvement of the condition in one patient, but was discontinued due to excessive skin side effects [5].

Individualized Treatment

• The choice of treatment needs to be individualized combined with prophylactic topical antibacterial and antifungal therapies [2].
• Regular hydration and skin care are also important for managing palmoplantar keratoderma [2].

It's worth noting that the material provided is not intended to replace professional medical care by a qualified specialist, and should not be used as a basis for diagnosis or treatment [8].

The differential diagnosis for KRT1-related diffuse nonepidermolytic keratoderma is broad and includes several conditions that may present with similar clinical features. Some of the key considerations in the differential diagnosis are:

• Aquagenic palmoplantar keratoderma: This condition is often seen in patients with cystic fibrosis, but can also occur in individuals without any underlying disease [6].
• Tinea corporis: A fungal infection that can cause a range of skin symptoms, including redness, itching, and blistering. In the differential diagnosis of KRT1-related diffuse nonepidermolytic keratoderma, it's essential to consider conditions like eczema, psoriasis, and annular erythema [7].
• Other forms of palmoplantar keratoderma: There are several other types of palmoplantar keratoderma that can be considered in the differential diagnosis, including epidermolytic palmoplantar keratoderma (EPPK) caused by mutations in the KRT9 gene [2].
• Genetic conditions: Certain genetic conditions, such as cystic fibrosis, may also present with skin symptoms similar to those seen in KRT1-related diffuse nonepidermolytic keratoderma.

It's worth noting that the diagnosis of KRT1-related diffuse nonepidermolytic keratoderma is typically based on a combination of clinical features and genetic testing [5]. A thorough evaluation by a healthcare professional, including a detailed medical history and physical examination, is essential to accurately diagnose this condition.

References: [2] - Diffuse epidermolytic PPK (EPPK; MIM# 144200, KRT9, KRT1) is the most common diffuse PPK [2]. [5] - Mode of inheritance: Diffuse non-epidermolytic palmoplantar keratoderma is an autosomal dominantly inherited condition traced to KRT1 and KRT16 keratins [5]. [6] - Aquagenic palmoplantar keratoderma (seen in patients with cystic fibrosis, but also occurs in individuals without any underlying disease) [6]. [7] - A number of different conditions should be considered in the differential diagnosis of tinea corporis, including eczema, psoriasis, and annular erythema [7].