congenital insensitivity to pain syndrome, Marsili type

Congenital insensitivity to pain syndrome, Marsili type is a condition affecting the sensory system in which individuals have a markedly reduced ability to feel pain, temperature, and to sweat. This disorder is caused by a mutation in the ZFHX2 gene and follows an autosomal dominant inheritance pattern, meaning that only one copy of the altered gene is sufficient to cause the condition. It is very rare, affecting fewer than 1 in 1,000,000 people, and can be observed in both males and females. Early recognition is important to avoid injuries and other complications arising from not perceiving pain normally.

The clinical features of this condition are centered on abnormal pain perception. Individuals characteristically exhibit insensitivity to pain, a decreased corneal reflex, and impaired temperature sensation, all of which are consistently reported. In addition, many individuals experience recurrent fever episodes, although not everyone may have this feature. Not all individuals experience all features, and severity varies considerably, highlighting the variable expressivity of the condition.

This condition is caused by mutations in the ZFHX2 gene, which plays an important role in normal sensory signal processing. It is inherited in an autosomal dominant manner, meaning that a single copy of the mutated gene can cause the disorder. As a result, an affected individual has a 50% chance of passing the altered gene to each child, which is important to consider in family planning. Genetic counseling is recommended to help families understand the implications of this inheritance pattern.

Currently, management focuses on supportive care and symptom management since there are no specific foundational therapies or approved treatments for congenital insensitivity to pain syndrome, Marsili type. Treatment is tailored to the individual’s needs and generally involves a multidisciplinary team to address complications like injuries or infections that may occur due to the lack of pain perception. Genetic counseling is recommended so that patients and families can discuss available options and strategies for managing the condition. Patients should discuss treatment options with their healthcare team to determine which approaches may be most appropriate for their specific situation.

The long‐term outlook for individuals with this condition is variable and depends on factors such as the severity of sensory impairment and access to specialized care. With current standards of care and vigilant management of injuries and complications, many individuals can lead a productive life. Outcomes described in medical literature continue to evolve as standards of care improve. Families often find it helpful to connect with genetic counselors and specialists familiar with this condition for guidance on ongoing management and future planning.