Congenital sensory neuropathy with anhidrosis is an extremely rare hereditary disease characterized by disorders of peripheral innervation and sweating processes. One of the main symptoms of this condition is the complete absence of nociceptive sensitivity, increased body temperature due to impaired thermoregulation, attacks of sudden shortness of breath. Diagnosis of the disease is based on physical examination data, checking the body’s response to various external stimuli, genetic studies. There is no treatment for congenital sensory neuropathy with anhidrosis, but patients require special care.
Congenital sensory neuropathy with anhidrosis (familial dysautonomia type 2, congenital insensitivity to pain with Swanson’s anhidrosis) is a very rare genetic pathology caused by disorders of innervation and nociceptive sensitivity. The first reports of this condition appeared in 1932, several families from Pakistan were found, whose members had complete insensitivity to pain, a tendency to self-harm and increased body temperature. To date, it is not possible to determine the occurrence of this disease due to its great rarity, in total about a hundred patients with congenital sensory neuropathy with anhidrosis have been described.
The mechanism of inheritance of this condition is autosomal recessive, men and women are affected with the same probability. For modern genetics and medicine in general, family dysautonomia type 2 is of great interest because of the disclosure of the genetic aspects of pain and the possibility on this basis to create a new generation of painkillers.
Two main genes have been identified, mutations in which are responsible for the development of this pathology. The first of them, NTRK1, is located on the 1st chromosome and encodes a special receptor of nerve tissues (tyrosine kinase receptor type 1). This protein is sensitive to the nerve growth factor and, if its structure is disrupted due to the mutation of the NTRK1 gene, it is not able to fully perform its functions. As a result, the development of cholinergic neurons, cells of the sympathetic nervous system, sensitive pathways in the posterior roots of the spinal cord is disrupted. The processes of myelination of peripheral fibers are also hindered. All this leads to the fact that it becomes impossible to cholinergic innervation of sweat glands and conduct painful nerve impulses while maintaining tactile, temperature and taste sensitivity. The mechanism of inheritance of mutations of the NTRK1 gene is autosomal recessive, according to some data, it is its defects that cause most cases of congenital sensory neuropathy with anhidrosis.
The second gene whose mutations are associated with this disease is SCN9A, localized on the 2nd chromosome. The product of its expression is a special protein (Nav1.7) belonging to the group of sodium channels of neurons. It was revealed that the largest number of such channels is observed on the membranes of neurons of the nociceptive system, but their specific functions are unknown there. The disease caused by a mutation of the SCN9A gene is also characterized by a complete loss of pain sensitivity, but other symptoms, such as fever, mental retardation, are much less pronounced. Therefore, clinically, the course of this form of congenital sensory neuropathy with anhidrosis is more favorable.
The leading symptom of this disease is the complete absence of nociceptive sensitivity – patients do not feel pain from birth and cannot even imagine this feeling. They can feel touch, cold, heat – but there are no painful sensations even in cases when a burn is already developing on the skin. Bone fractures, injury to the skin and other parts of the body can be felt, but patients do not describe their feelings as unpleasant. As a result, autoaggression is often observed in their childhood – especially often patients bite their lips, tongue, and can cause other injuries to themselves. This may persist into adulthood, especially if congenital sensory neuropathy with anhidrosis is accompanied by mental retardation – this is typical for conditions caused by mutations of the NTRK1 gene.
Patients constantly have an elevated body temperature, sometimes with episodes of fever up to 40-41 ° C, which does not respond to taking traditional antipyretics. This is due to sweating disorders, as a result of which the usual cooling of the body does not occur. For the same reason, changes in the skin are also observed – they are hot and dry to the touch, the skin itself is thin, often easily gathers into folds. Among other, less permanent symptoms of congenital sensory neuropathy with anhidrosis, there is early tooth loss, an increased risk of osteomyelitis, necrosis of bones and joints. The reason for these changes lies in violations of innervation of a number of structures, an important role is played by the later treatment of patients to a specialist – one of the symptoms of osteomyelitis or bone necrosis is pain that patients are not able to feel. In rare cases, ophthalmic disorders may be detected – keratoconus, the presence of erosions and corneal ulcers.
To determine this condition, a variety of techniques are used – physical examination, diagnostic tests to detect anhidrosis, genetic studies, and the study of hereditary anamnesis. When examining patients, signs of autoaggression are often revealed – severely damaged lips and tongue with traces of teeth (up to the absence of part of it), there may be fresh and old cuts on the body and limbs, signs of healed fractures. However, damage to the skeleton or muscles may also be due to the fact that during physical exertion, patients are not able to correctly assess the effort and at the same time tear muscles, ligaments or break bones. The body temperature is elevated, the skin is dry, mental retardation of varying degrees may occur. Patients feel touch, have normal temperature sensitivity, but needle injections are not perceived as pain, but rather evaluate them as a variant of touch.
During diagnostic tests, there are no sweat reactions to any stimuli – electrical stimulation or pilocarpine test are completely negative. When the ambient temperature rises, sweating also does not occur, but the patient’s body temperature begins to rise due to difficult heat transfer. Electromyography does not detect conduction disturbances, all reflexes are completely preserved except for the corneal one – it is sharply reduced or even absent, this is one of the important signs of congenital sensory neuropathy with anhidrosis.
The study of the hereditary history often confirms the familial nature of the disease, genetic diagnosis is reduced to direct sequencing of the NTRK1 gene in order to identify mutations. Some laboratories are able to perform a similar procedure for the SCN9A gene. A geneticist can also search for a pathological gene in phenotypically healthy carriers (in the case of congenital sensory neuropathy with anhidrosis in relatives) or carry out prenatal diagnosis by amniocentesis or biopsy of chorionic villi.
Treatment and prognosis
There is no specific treatment for congenital sensory neuropathy with anhidrosis. From early childhood, special care is needed for patients – to prevent self-harm (biting of lips, tongue), carefully monitor the state of the musculoskeletal system, control body temperature. With the development of fever or overheating, it is possible to eliminate hyperthermia only by physical methods – a cold shower, using ice bubbles, wiping with cold water. If there are signs of oligophrenia, then the patient should be under constant supervision, in the case of preserved intelligence, an adult with such a disease can theoretically control his own disease. With proper care and a healthy lifestyle, the prognosis regarding the patient’s life is favorable.