Expert Reviewed By: Dr. Brandon Colby MD
What is Palmoplantar Keratoderma (PPK)?
Palmoplantar keratoderma (PPK) is a group of skin disorders characterized by the thickening of the skin on the palms of the hands and the soles of the feet. This thickening can cause discomfort, pain, and difficulty walking or using the hands. PPK can be either acquired or genetic, with varying levels of severity and symptoms. A better understanding of the genetic causes of PPK can help in the diagnosis, management, and treatment of this not-so-rare disease [1].
Genetic Causes of PPK
Genetic PPK is caused by mutations in specific genes that affect the normal functioning of the skin. Several genes have been identified as responsible for different forms of PPK, including AQP5, KRT9, KRT1, and desmoplakin [2] [3]. In some cases, genetic PPK can also be associated with other health conditions, such as dilated cardiomyopathy, a heart condition that can lead to heart failure [3].
Diagnosing PPK
Diagnosing PPK typically involves a thorough physical examination, including a close look at the affected areas of the skin. In some cases, a skin biopsy may be needed to confirm the diagnosis. If a genetic cause is suspected, molecular genetic testing can be performed to identify the specific gene mutation responsible for the condition [2].
Benefits of Genetic Testing for PPK
Genetic testing can be helpful in several ways for individuals with PPK and their families:
- Confirming the diagnosis: Identifying the specific gene mutation responsible for PPK can confirm the diagnosis and help to differentiate between acquired and genetic forms of the condition.
- Guiding treatment: Understanding the genetic cause of PPK can help healthcare providers develop a personalized treatment plan that targets the underlying genetic defect.
- Identifying at-risk family members: If a genetic mutation is identified in an individual with PPK, family members can also be tested to determine if they carry the same mutation and are at risk for developing the condition.
- Screening for associated health conditions: In some cases, genetic PPK can be associated with other health conditions, such as dilated cardiomyopathy [3]. Genetic testing can help identify individuals who may be at risk for these associated conditions and allow for early intervention and management.
Recent Research and Discoveries
Recent studies have identified new genetic mutations responsible for PPK and have shed light on the underlying mechanisms of the disease. For example, a study published in 2021 identified pathogenic CTSZ gene variants as a cause of focal PPK and demonstrated their impact on EGFR expression and keratinocyte proliferation [4]. This research not only helps to improve our understanding of PPK but also opens up new avenues for potential treatment strategies targeting these genetic mutations.
Conclusion
Understanding the genetic causes of palmoplantar keratoderma is crucial for accurate diagnosis, management, and treatment of this skin disorder. Genetic testing can play a significant role in identifying the specific gene mutations responsible for PPK and guiding personalized treatment plans. As research continues to uncover new genetic mutations and their roles in PPK, the potential for improved treatment options and better outcomes for individuals with this condition will only continue to grow.
About The Expert Reviewer
Dr. Brandon Colby MD is a US physician specializing in the personalized prevention of disease through the use of genomic technologies. He’s an expert in genetic testing, genetic analysis, and precision medicine. Dr. Colby is also the Founder of and the author of Outsmart Your Genes.
Dr. Colby holds an MD from the Mount Sinai School of Medicine, an MBA from Stanford University’s Graduate School of Business, and a degree in Genetics with Honors from the University of Michigan. He is an Affiliate Specialist of the American College of Medical Genetics and Genomics (ACMG), an Associate of the American College of Preventive Medicine (ACPM), and a member of the National Society of Genetic Counselors (NSGC)