Hereditary Sensory and Autonomic Neuropathies (HSAN) and Congenital Insensitivity to Pain (CIP) are rare disorders that, besides several other symptoms, lead to a reduced or even absent sensation of pain. At first, this sounds like a desirable condition – but upon a closer inspection one will realize that pain, even though it makes us feel uncomfortable, is a crucial warning signal of our body. Pain notifies our brain of injuries, inflammation, or extreme temperatures, thereby protecting us from further harm and informing us of problems which may require medical treatment.
Patients with CIP show a lack of pain perception at birth. Since these patients have never experienced pain, they are unaware of situations that may cause bodily harm as well as instances in which injury has occured. Severe injuries, such as bone fractures or burns, may therefore go unnoticed and will not receive the medical attention they require. Medical attention is essential to repair the damage and prevent further deterioration.
Later-onset forms of HSAN develop gradually in life. In addition to the decreasing sensation of pain, patients often show ulcerations, poor wound-healing or an impaired ability to walk. Autonomic symptoms like decreased sweating, maldigestion or unsteady blood pressure may also occur.
HSAN and CIP are monogenetic diseases, this means that the defect of a single gene in the DNA is enough to cause the disease. Thus far, researchers have linked ~20 genes to the development of HSAN/CIP. The large number of different disease-associated genes is reflected in the wide spectrum of clinical phenotypes, as different biological processes in the cell can be disturbed depending on the altered gene.
Due to the variety of subtypes of HSAN/CIP, no consensus guidelines on the diagnosis of these disorders exist. Ideally, the clinical examination should include a detailed record of the medical history with information on symptoms, age of onset, and previous illnesses and infections. In HSAN, differential diagnoses such as diabetic or amyloidosis-induced polyneuropathy should be excluded.
In addition to a clinical examination, genetic testing is required to confirm the clinical diagnosis of HSAN/CIP and is usually carried out on a patient’s blood sample. Panel sequencing is a fast and relatively cost-effective method to detect variants in all HSAN/CIP genes which are potentially causative for the disease. More sophisticated, next generation sequencing (NGS) approaches not only cover the already known HSAN/CIP genes but also provide the possibility to detect novel disease-associated genes.
The participation in international research projects or clinical trials may be an opportunity for patients from rural areas or low-income countries, where access to comprehensive clinical care and genetic testing is limited.
As for most genetic disease, no strategies to prevent the development of HSAN/CIP exist. Family members may also be at higher risk to develop the disease and should be offered genetic counseling. Except for a small number of targeted therapies for specific HSAN subtypes which are currently investigated in preclinical trials, only symptomatic treatment options exist.
For CIP patients, education about potentially harmful situations and stimuli is the most essential. E.g., the patients have to learn how to prevent burns or colds and what to do once an injury has happened. Patients who additionally present with intellectual disability may have difficulties to learn this behaviour. Help from doctors and patient organizations for the patients and their families is therefore crucial.
For a patient’s perspective on living a life with CIP, please have a look here.
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