PEPD

Paroxysmal Extreme Pain Disorder (PEPD), formerly known as Familial Rectal Pain Syndrome, is a rare neurological condition characterized by episodes of severe pain in various parts of the body, including the rectal, ocular, and mandibular areas. The disorder is caused by mutations in the SCN9A gene, which encodes the Nav1.7 sodium channel. This channel is crucial for the transmission of pain signals in the peripheral nervous system. PEPD is inherited in an autosomal dominant manner, meaning a single copy of the altered gene in each cell is sufficient to cause the disorder.

Symptoms

The hallmark of PEPD is the sudden onset of excruciating pain that can last from seconds to minutes. These pain attacks can be triggered by factors such as bowel movements, eating, stress, or changes in temperature. The pain is often described as sharp, stabbing, or burning. In addition to pain, individuals with PEPD may experience skin flushing, particularly in the affected area, tearing or redness of the eyes during ocular attacks, and a feeling of warmth or swelling in the mandibular region during jaw attacks.

Genetics

PEPD is caused by mutations in the SCN9A gene, which is located on chromosome 2q24.3. The SCN9A gene provides instructions for making the alpha subunit of the Nav1.7 sodium channel. This channel plays a key role in the transmission of pain signals. Mutations in the SCN9A gene alter the function of the channel, making it more easily activated and leading to the increased transmission of pain signals.

Diagnosis

Diagnosis of PEPD is based on the clinical presentation of the disorder, including the characteristic pattern of pain episodes and their triggers. Genetic testing can confirm a diagnosis by identifying a mutation in the SCN9A gene. However, not all individuals with the clinical symptoms of PEPD will have an identifiable mutation in this gene.

Treatment

There is no cure for PEPD, and treatment focuses on managing symptoms and improving quality of life. Medications that have been found to be effective in some cases include carbamazepine and mexiletine, which are used to treat neuropathic pain by stabilizing the activity of sodium channels. Other treatment strategies may include local anesthetics and lifestyle modifications to avoid known triggers.

Prognosis

The prognosis for individuals with PEPD varies. While the disorder does not typically affect life expectancy, the severity and frequency of pain episodes can have a significant impact on quality of life. With appropriate management, many individuals with PEPD are able to find relief from their symptoms and lead active lives.