[Congenital insensitivity to pain: clinical and neurophysiological study in three sisters of a Moroccan family]. / Insensibilité congénitale à la douleur, étude clinique et neurophysiologique chez 3 sœurs marocaines.

Congenital insensitivity to pain is a rare hereditary sensory and autonomic neuropathy (HSAN). This disorder is an autosomal recessive condition: since 1996, mutations attributed to this entity have been found in the neurotrophin tyrosine-kinase gene receptor on chromosome 1. The authors report 3 cases of congenital insensitivity to pain. In these 3 sisters of consanguineous parents, the clinical investigation showed total absence of pain and temperature sensations with preservation of all other sensory modalities, mental retardation, but in contrast to HSAN type IV, there was no anhidrosis. The neurophysiological investigation revealed an isolated axonal sensory polyneuropathy in the 3 patients. The clinical and neurophysiological investigations were normal in both parents and the brother. The physiopathology of this entity is discussed. We suggest a particular form of HSAN type IV with preservation of transpiration or a new entity of congenital insensitivity to pain, which should be analyzed genetically.

[Congenital insensitivity to pain]. / L'insensibilité congénitale à la douleur.

Congenital insensitivity to pain (CIP) is a rare syndrome with various clinical expressions, characterized by a dramatic impairment of pain perception since birth. In the 1980s, progress in nerve histopathology allowed to demonstrate that CIP was almost always a manifestation of hereditary sensory and autonomic neuropathies (HSAN) involving the small-calibre (A-delta and C) nerve fibres which normally transmit nociceptive inputs along sensory nerves. Identification of the genetic basis of several clinical subtypes has led to a better understanding of the mechanisms involved, emphasizing in particular the crucial role of nerve growth factor (NGF) in the development and survival of nociceptors. Recently, mutations of the gene coding for the sodium channel Nav1.7--a voltage-dependent sodium channel expressed preferentially on peripheral nociceptors and sympathetic ganglia--have been found to be the cause of CIP in patients showing a normal nerve biopsy. This radical impairment of nociception mirrors the hereditary pain syndromes associated with "gain of function" mutations of the same ion channel, such as familial erythromelalgia and paroxysmal extreme pain disorder. Future research with CIP patients may identify other proteins specifically involved in nociception, which might represent potential targets for chronic pain treatment. Moreover, this rare clinical syndrome offers the opportunity to address interesting neuropsychological issues, such as the role of pain experience in the construction of body image and in the empathic representation of others' pain.

Two brothers with a variant of hereditary sensory neuropathy.

We report two brothers with the clinical symptoms and neuropathological findings of hereditary sensory and autonomic neuropathy (HSAN) type IV but with normal sweating function and absence of recurrent fever. We propose that our patients may have a lower degree of expression of the genetic defect underlying HSAN type IV or that they represent a separate genetic entity.

[A case of congenital insensitivity to pain with destructive arthropathies of the limbs and spine. Discussion on nosology and physiopathology of the disease]. / Etude d'un cas d'insensibilité congénitale à la douleur avec arthropathies destructrices des membres et du rachis. Discussion à ce propos de la nosologie et de la physiopathologie de l'affection.

A seventeen year old boy presented with destructive arthropathy of the lower limbs and discovertebral spaces. Past history yielded recurrent episodes of indolent fractures and progressive knee and ankle deterioration. The patient denied any pain sensation in the past and at examination. Other neurological tests were normal. Beta-endorphin level was elevated in the CSF. Response to the cold pressor test was modified after injection of Naloxone. The nosology and physiopathology of congenital insensitivity to pain are discussed.

Clinical manifestations of congenital insensitivity of the hand and classification of syndromes.

Lesions of the upper extremity, particularly of the hand, are common in congenital insensitivity syndromes. Five cases are described with findings including fractures, infections, stiffness of fingers, self-mutilation, and traumatic amputations. The best form of treatment is preventative, since reconstructive surgery has little to offer. If conservative efforts are of no avail, amputation of the part is, unfortunately, the best way to obtain satisfactory results.