Pseudoxanthoma elasticum, dominant form

Pseudoxanthoma Elasticum, Dominant Form (PXE) is a rare genetic disorder that affects the connective tissue in some parts of the body. PXE is characterized by the progressive calcification, fragmentation, and degeneration of elastic fibers, primarily affecting the skin, eyes, and cardiovascular system. The dominant form of PXE implies that the condition follows an autosomal dominant pattern of inheritance, meaning a single copy of the altered gene in each cell is sufficient to cause the disorder. However, it's important to note that the majority of PXE cases are actually autosomal recessive, making the dominant form exceedingly rare.

Symptoms

The symptoms of PXE vary widely among individuals but typically include:

• Skin Changes: Yellowish papules or plaques, often appearing on the neck, underarms, and other flexural areas, are hallmark signs. These skin changes are due to the accumulation of altered elastic fibers in the dermis.
• Eye Problems: Individuals may experience changes in their vision due to the development of angioid streaks in the retina, which can lead to choroidal neovascularization and, potentially, vision loss.
• Cardiovascular Issues: PXE can lead to increased rigidity of blood vessels, contributing to hypertension, coronary artery disease, and other cardiovascular complications.

Causes

PXE is primarily caused by mutations in the ABCC6 gene, which plays a role in the transport of ATP-binding cassette substrates across cell membranes. In the dominant form, a single mutated copy of the ABCC6 gene from one parent is sufficient to cause the disorder. The exact mechanism by which ABCC6 mutations lead to the symptoms of PXE is not fully understood, but it is believed to involve the improper mineralization of elastic fibers in the connective tissue.

Diagnosis

Diagnosis of PXE is based on a combination of clinical examination, family history, and genetic testing. Skin biopsy can confirm the presence of characteristic changes in the elastic fibers. Genetic testing for mutations in the ABCC6 gene can provide a definitive diagnosis.

Treatment

There is no cure for PXE, and treatment focuses on managing symptoms and preventing complications. This may include:

• Regular monitoring of the eyes by an ophthalmologist to detect and treat any complications early.
• Management of cardiovascular risk factors, such as hypertension and hyperlipidemia, to reduce the risk of cardiovascular disease.
• Use of photoprotection to protect the skin from damage and potentially slow the progression of skin symptoms.

Prognosis

The prognosis for individuals with PXE varies depending on the severity of the symptoms and the effectiveness of management strategies. While PXE can significantly impact quality of life, with appropriate management, many individuals with the condition can lead long and productive lives.