Decoding Darier Disease: Acral Hemorrhagic Type and the Role of Genetic Testing

Expert Reviewed By: ⁠Dr. Brandon Colby MD

Darier disease is a rare genetic skin disorder characterized by the development of small, hard, raised spots on the skin. These spots, known as keratotic papules, often have a warty appearance and can become itchy or painful. The acral hemorrhagic type of Darier disease is a less common form that presents with painful, bleeding skin lesions on the hands and feet. This article will explore the current understanding of Darier disease, particularly the acral hemorrhagic type, and discuss the importance of genetic testing in diagnosing and managing this condition.

Understanding Darier Disease

Darier disease is caused by mutations in the ATP2A2 gene, which is responsible for encoding a protein called SERCA2. This protein plays a crucial role in maintaining the correct balance of calcium ions within skin cells, which is essential for the normal functioning of these cells. When the ATP2A2 gene is mutated, the resulting abnormal protein disrupts calcium homeostasis, leading to the characteristic skin abnormalities seen in Darier disease.

There are two main types of Darier disease: the more common non-segmental type and the less common segmental type. The acral hemorrhagic type is a variant of the segmental form, which is characterized by the presence of painful, bleeding skin lesions on the hands and feet. This type of Darier disease has been shown to be caused by mutations in the ATP2A2 gene, but not necessarily in exon 15, as previously thought (source).

Diagnosing Darier Disease

The diagnosis of Darier disease is typically based on the clinical presentation of the characteristic skin lesions, along with a thorough medical history and physical examination. However, due to the rarity and variable presentation of this condition, it can sometimes be challenging to differentiate Darier disease from other similar skin disorders, such as Hailey-Hailey disease. In such cases, genetic testing can play a crucial role in confirming the diagnosis and guiding appropriate treatment.

Genetic Testing for Darier Disease

Genetic testing involves analyzing a person’s DNA to identify specific genetic mutations associated with a particular condition. In the case of Darier disease, genetic testing can be used to detect mutations in the ATP2A2 gene, providing a definitive diagnosis. This can be particularly helpful when the clinical presentation is atypical or when other skin disorders are being considered as possible diagnoses.

For example, a recent study on a case of type 1 segmental Darier disease with a p.P160L mutation in ATP2A2 showed that genetic testing was instrumental in confirming the diagnosis and guiding appropriate treatment (source).

Genetic Testing for Differential Diagnosis

In some cases, genetic testing can also be used to differentiate Darier disease from other similar skin disorders. For example, a study on the differential expression of STIM1 and ORAI1 proteins showed that the subcellular compartmentalization of these proteins could be used to distinguish Darier disease from Hailey-Hailey disease (source).

Using Genetic Testing to Inform Treatment and Management

In addition to confirming the diagnosis of Darier disease, genetic testing can also provide valuable information to guide treatment and management decisions. By identifying the specific genetic mutation responsible for a patient’s condition, healthcare providers can better predict the likely course of the disease and tailor treatment plans accordingly.

Furthermore, genetic testing can be useful in identifying at-risk family members who may also carry the mutated gene, allowing for early intervention and management of the condition. This can be particularly important in cases of late-onset Darier disease, as highlighted in a case series on segmental type 1 Darier disease (source).

Conclusion

Darier disease, particularly the acral hemorrhagic type, is a rare and complex genetic skin disorder that can be challenging to diagnose and manage. Genetic testing plays a crucial role in confirming the diagnosis, differentiating it from other similar skin conditions, and guiding appropriate treatment and management strategies. As our understanding of the genetic basis of Darier disease continues to evolve, genetic testing will undoubtedly remain an essential tool in the ongoing quest to improve the lives of those affected by this condition.

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)