Congenital insensitivity to pain (CIP) refers to group of rare hereditary sensory and autonomic neuropathies (HSANs) characterised by an inability to feel pain 1.
Although not clearly defined in the literature, CIP is not one specific diagnosis, but describes symptoms common to many HSANs. There are currently seven types of HSAN, including similarly-named diagnoses to CIP such as congenital insensitivity to pain with anhidrosis (HSAN4) 1. However, some authors use "CIP" to refer to a specific type of HSAN, that being HSAN2D 2. This article uses CIP broadly to describe features common to all HSAN types.
Generally, all HSAN patients with CIP have recurrent, painless, and often unrecognised musculoskeletal injuries that start in early childhood, sometimes initially misdiagnosed as non-accidental injuries 1-7. The recurrent and unaware nature of these injuries can result in untreated fractures, joint destruction, osteomyelitis, septic arthritis, avascular necrosis, and Charcot arthropathies 1-7. Many patients also have injuries as a result of self-infliction 3-7.
Depending on the specific type of HSAN that a patient may have, they may have other symptoms 1. For example, patients with HSAN2D may additionally have anosmia, and patients with HSAN4 may additionally have anhidrosis 1,4,7.
The aetiology and pathogenesis of CIP depends on the specific type of HSAN. For example:
- HSAN2D (channelopathy-associated congenital insensitivity to pain): patients have homozygous mutations in the SCN9A gene 4,7. This gene encodes for the alpha subunit of a sodium channel (NaV1.7) that is important in peripheral nociception and olfactory nervous pathways 4,7. Dysfunction in these channels results in dysfunction in these pathways, leading to the characteristic clinical features of CIP and anosmia 4,7.
- HSAN4 (congenital insensitivity to pain with anhidrosis): patients have homozygous mutations in the NTRK1 gene 1. This gene encodes for the receptors for a nerve growth factor that normally promotes survival of embryonic sensory and sympathetic neurons 1. Dysfunction in this factor results in sensory and sympathetic dysfunction, resulting in CIP and anhidrosis clinically 1.
- HSAN7: patients have mutations in the SCN11A gene, and develop CIP via a similar mechanism to HSAN2D 6.
There are a large variety of potential radiographic features depending on where and when injuries have been sustained 3,8.
Treatment and prognosis
No specific treatment is available for CIP 1,7. Management focuses on lifestyle and education interventions with an aim of preventing further injuries, and in quickly identifying and treating injuries if they do occur 1,6,7.
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