Hereditary Sensory and Autonomic Neuropathies (HSAN) and Congenital Insensitivity to Pain (CIP) are rare disorders which result in the loss of pain as well as a variety of additional symptoms.

The rarity of the disorders results in small patient cohorts, a lack of standardized phenotypic information and low awareness, even among professionals, raising major hurdles for clinicians and scientists in treatment and research. As a result, patients and families often go through an odyssey of medical consultations and several years can pass until the diagnosis is made.

To overcome this, seven European research centers which focus on HSAN/CIP and two patient organizations have formed the European Network on Inherited Sensory Neuropathies and Insensitivity to Pain (ENISNIP). We aim to increase awareness of these rare disorders and to accelerate genetic testing and the discovery of new genes to improve patient care and diagnostics for long term.

Standardize data

The main problem that medical professionals and scientists face when dealing with rare diseases is the small number of patients who are treated all around the world. Thus, there is no standardized approach to diagnose or treat HSAN/CIP. Also, the documentation of patients’ symptoms varies massively. This hampers the treatment of patients and the research on causes and potential therapies in the long term. By networking between clinicians and scientists, we aim to ensure that both clinical and genetic data are collected in a standardized manner, e.g., by using the same clinical questionnaires and similar bioinformatics pipelines.

Identify novel disease-causing mechanisms

We want to collect the standardized data in a database to which scientists and clinicians from other sites will also have access, certainly under strict data protection. In this way, the group size of patients with standardized genetic and clinical data will be increased, enhancing the probability of detecting thus far unknown disease-causing mechanisms. The better understanding of the disease can then help to improve diagnosis and treatment of patients with HSAN/CIP, which we see as our overall goal.

Here you find reports from patiens and families about their lives with CIP. You are affected and would like to share your story? Then simply get in touch with us.

From a discussion with a family with a boy with SCN11A-related CIP

“Our eldest of three sons has felt no pain since birth. But that’s not quite true for him. Sometimes he has severe pain in his feet that lasts for 30–60 seconds, which is unbearable. He can also perceive showers and warm drops of water on his skin as extremely unpleasant. On the other hand, he breaks his thigh bone without it causing him any pain. He is very social and has an extremely good sense of humour. He is cheerful. He has hobbies like all 16-year-old boys. He likes computer games, mountain biking and meeting friends.

But he has plenty of medical problems. When he is sick, it normally means he is really sick. Broken bones, operations, bone infections and his poor wound healing have led to a leg length discrepancy that makes walking difficult. He has an insatiable itch, so that he inflicts extensive wounds on himself by scratching and rubbing. He inflicted large mutilations on his nose when he was still a child. When people look and talk because of his mutilations, he says, let them look, I don’t mind. It hurts us as parents, but he copes admirably and that is a real strength of him. Weight gain is extremely difficult due to his gastrointestinal motility disorder, he has a sweat regulation disorder, continence problems and he still often bites his fingernails completely.

Specialists from various disciplines take care of each of his medical needs, but often one does not talk to the other. What we have always lacked enormously and what would be a great help for him and for us is a central contact person who simply keeps an eye on him, who knows him, who directs his medical care and keeps the specialists mutually informed. This aspect becomes even more relevant if the transition into adulthood is to succeed. This is where we are really concerned. We need the linking of the various doctors and constant care by a central contact point. Respective structures are obviously neglected in our health system.”

(published in Lischka A, Lassuthova P, Çakar A, Record CJ, Van Lent J, Baets J, Dohrn MF, Senderek J, Lampert A, Bennett DL, Wood JN, Timmerman V, Hornemann T, Auer-Grumbach M, Parman Y, Hübner CA, Elbracht M, Eggermann K, Geoffrey Woods C, Cox JJ, Reilly MM, Kurth I. Genetic pain loss disorders. Nat Rev Dis Primers. 2022 Jun 16;8(1):41. doi: 10.1038/s41572-022-00365-7. PMID: 35710757)

Patient advocacy organization for patients with inherited polyneuropathy in Austria (CMT-Austria)

Patient advocacy organization for patients with inherited polyneuropathy in the Czech Republic (Společnost C-M-T)

If you are affected with CIP/HSAN and would like to be registered in the ENISNIP database, please use the form below. We will then get in touch with you and coordinate the next steps.

Please note: This is a first non-binding request without any obligation. You can withdraw your request at any time.

How can CIP/HSAN be distinguished from other neuropathic pain disorders?
CIP and HSAN are characterized by the absence of pain sensation or impairment of temperature perception, while other neuropathic disorders are typically associated with pain, numbness, or paresthesia. A detailed medical history, neurological tests, and genetic examinations are crucial for differentiation.

What pathophysiological mechanisms underlie CIP/HSAN?
Most cases of CIP and HSAN result from disturbances in nerve function, particularly in pain and temperature perception. CIP/HSAN are genetic disorders and pathogenic variants are commonly found in the SCN9A gene, causing dysfunction of the Nav1.7 ion channel or NTRK1, which are both essential for pain perception in nerve cells. However, to date more than 20 genes have been identified to be causative for CIP/HSAN affecting various cellular processes, wherefore a broad genetic testing approach is the method of choice in diagnosing these rare diseases.

Which genetic tests are required for the diagnosis of CIP/HSAN?
Since more than 20 genes are known to be associated with CIP/HSAN, broad genetic testing should ideally be performed (at least panel sequencing, preferably exome sequencing). Simultaneous testing of affected and unaffected family members increases the likelihood of a definitive diagnosis. Furthermore, extensive testing involving multiple family members in a research context provides an opportunity to uncover additional previously unknown mechanisms, thereby contributing to a better understanding of these ultra-rare diseases and pain perception in general.

Is there a cure for CIP/HSAN?
Currently, there is no cure for CIP or HSAN. Treatment focuses on symptom management, prevention of injuries and complications, and alleviating functional disorders of the autonomic nervous system.

What therapeutic approaches are available for patients with CIP/HSAN?
Treatment includes preventive measures to avoid injuries (e.g., regular skin inspections and safety precautions), pain management for secondary symptoms (such as autonomic dysfunction), as well as physiotherapeutic and occupational therapy to improve quality of life.

What complications can arise with CIP/HSAN?
Since patients do not feel pain, there is an increased risk of unnoticed injuries, chronic wounds, and infections. Other complications may include autonomic dysfunctions like blood pressure fluctuations, digestive problems, and urinary issues, which need to be regularly monitored.

What advances have been made in research on CIP/HSAN?
Research on CIP and HSAN focuses on uncovering the genetic causes and developing therapies to restore normal pain sensation or treat associated conditions like autonomic disorders. Gene-edited models and studies on ion channels and nerve growth factors are promising approaches.

How can doctors and scientists improve the quality of life for patients with CIP/HSAN?
Through early diagnosis and preventive measures, doctors can help avoid injuries and improve quality of life. Regular check-ups to monitor the disease course, as well as interdisciplinary care that includes physiotherapy and nutritional advice, are important to optimize the functionality and well-being of patients.

What is the ENISNIP Registry database useful for?
The ENISNIP Registry enables the collection of extensive and standardized data that can be used to analyze disease patterns, treatment responses, and outcomes of CIP/HSAN. Researchers and doctors can benefit from the registry to develop better diagnostic methods, monitor the effectiveness of treatments, and test new therapeutic approaches. Given the rarity of CIP and HSAN, the registry offers a unique opportunity to compare patient data on a broader scale, fostering scientific collaboration and leading to new insights that might not otherwise be possible due to the limited number of cases.

I have a patient whom I would like to include in the ENISNIP register. Who can I contact? For informal contact and further information on registering, please see “Register here”.

What is CIP/HSAN?
CIP (Congenital Insensitivity to Pain) and HSAN (Hereditary Sensory and Autonomic Neuropathy) are rare genetic disorders where affected individuals do not feel pain. HSAN encompasses a group of neurological disorders that can also cause other symptoms, such as motor abnormalities and autonomic dysfunction.

What symptoms occur in CIP/HSAN?
Typical symptoms include the absence of pain sensation, difficulties in temperature perception, repeated injuries without pain response, and possibly problems with the autonomic nervous system, such as blood pressure fluctuations or digestive disorders.

Why is it dangerous not to feel pain?
Pain is an important warning mechanism in the body. People with CIP/HSAN may not immediately recognize injuries or health issues, which can lead to serious harm. This can result in untreated wounds, fractures, or even infections. Parents of affected children should closely monitor them, especially during activities that could lead to injury. Regular medical check-ups are important, as well as home safety precautions, such as soft furniture and protection from heat and cold.

How is CIP/HSAN diagnosed?
When CIP/HSAN is suspected based on symptoms, genetic testing should be performed, along with clinical examinations, nerve tests, and family history review to determine if the symptoms point to CIP or a form of HSAN.

What role do genetic tests play?
Genetic tests are essential to determine if a person is a carrier of CIP or HSAN and to identify the exact genetic variation. This helps in better understanding the disease and potentially provides an earlier diagnosis for other affected family members.

Can CIP/HSAN be cured?
Currently, there is no cure for CIP or HSAN. Treatment focuses on symptom relief and preventing complications, such as raising awareness about the dangers of unnoticed injuries and improving quality of life.

What medical support is needed?
Affected individuals require regular monitoring by doctors who specialize in neurology and pain management. In some cases, specialized physiotherapy or occupational therapy can helpful to promote motor skills.

How does CIP/HSAN affect life in adulthood?
In adulthood, affected individuals may have a normal life expectancy but may need support in monitoring wounds, infections, and other health issues. Their ability to perform everyday activities safely often requires adjustments and precautions.

Is there support for families and individuals with CIP/HSAN?
Yes, there are support groups, organizations, and specialists who offer both emotional support and practical advice on medical, therapeutic, and safety-related aspects of living with CIP/HSAN and other neuropathies. For more information, please see “Patient advocacy organizations”.

What is the ENISNIP Registry database useful for?
The ENISNIP Registry is a database where information about your/your relative’s condition is stored securely and confidentially. Since CIP/HSAN are ultrarare disorders, the participation of affected individuals is crucial in helping to improve research and understanding of these diseases. It assists doctors and researchers in developing better treatment options and supports the scientific community in better understanding the causes and progress of these rare disorders. Your data helps improve medical care for future patients who may also be affected by these conditions.

I would like to become registered / would like my child to be registered in the ENISNIP database. Who can I contact?
For informal contact and further information on registering, please see “Register here”.