congenital insensitivity to pain-hypohidrosis syndrome

Congenital insensitivity to pain-hypohidrosis syndrome is a hereditary sensory neuropathy that primarily affects the nerves responsible for sensing pain and temperature, as well as those regulating sweat and tear production. The condition results from a homozygous mutation in the PRDM12 gene, which plays a key role in the development of pain-sensing neurons. It is inherited in an autosomal recessive manner and is extremely rare, affecting fewer than 1 in 1 million people. Although symptoms usually present early in life, the severity and specific manifestations can vary widely between individuals.

Individuals with congenital insensitivity to pain-hypohidrosis syndrome characteristically exhibit an inability to feel pain and impaired temperature sensation, which are consistently observed. Other common clinical features include decreased sweating (hypohidrosis), reduced tear production (decreased lacrimation), and recurrent skin infections. Some patients may also experience additional sensory deficits such as hypoesthesia, impaired proprioception, impaired vibratory sensation, and hyporeflexia. In a subset of affected individuals, cognitive challenges including intellectual disability have been reported. Not all individuals experience every feature, and severity varies considerably.

The genetic basis of this syndrome is a mutation in the PRDM12 gene, a critical gene involved in the formation and maintenance of sensory neurons. The condition is inherited in an autosomal recessive pattern, meaning that an individual must inherit two copies of the mutated gene—one from each parent—to manifest the disease. As is often the case with rare autosomal recessive conditions, it may be more common when parents share a common ancestor, which increases the probability that both carry the same rare variant. Families are advised to consider genetic counseling to better understand the implications and recurrence risks for future pregnancies.

Currently, management focuses on supportive care and symptom management, as there are no treatments specifically approved for congenital insensitivity to pain-hypohidrosis syndrome. A multidisciplinary team is often involved in addressing the array of symptoms, which may include measures to protect the skin, manage infections, and ensure eye care to prevent complications from corneal scarring. Regular surveillance is an essential part of long-term care, helping to identify complications early and allowing for timely intervention. Patients should discuss treatment options with their healthcare team, and genetic counseling is recommended for affected families to understand their risks and management options.

The long-term outlook for congenital insensitivity to pain-hypohidrosis syndrome varies significantly among individuals. With current standards of care, many individuals live into adulthood, although the condition remains lifelong and requires ongoing management. Outcomes described in medical literature continue to evolve as standards of care improve, and severity and symptoms vary widely between individuals. Families are encouraged to seek genetic counseling and connect with specialists experienced in managing the condition to help navigate the challenges and optimize care over time.

Clinical trials are underway exploring new treatment approaches for this condition. Individuals interested in clinical trials can search ClinicalTrials.gov or consult their care team about eligibility.