Congenital Insensitivity to Pain and Anhydrosis Syndrome.

Sir,

A 2-year-old girl presented to our polyclinic with skin dryness, recurrent fever, anhydrosis and nonhealing scars on the elbows and the palms. The patient had a history of anhydrosis, lack of pain sensation, and recurrent fever episodes since birth. The patient bit and hurt her fingers twice within the last 6 months due to the lack of pain sensation. The patient had no family history of genetic disorders and her parents were first-degree cousins. Dermatological examination revealed xerosis in the whole body, ulcers on the fingertips and the palms, and a hyperkeratotic ulcerated lesion on the right patella. Anonychia was present in the right thumb [Figures 1 and 2]. Hair examination was normal. Hematological and biochemical parameters were within normal ranges. Based on the clinical findings, the patient was diagnosed as having congenital insensitivity to pain and anhydrosis (CIPA) syndrome.

Figure 1

There are ulcerated areas in the fingertips and in the palm with anonychia on the right thumb

Figure 2

There is seen hyperkeratotic ulcerated lesion on the right knee

CIPA syndrome is a rare autosomal recessive disorder characterized by congenital insensitivity to pain, anhydrosis, recurrent fever episodes, and self-destructive behaviors.[1] The incidence of CIPA is 1 in 125 million newborns. CIPA is caused by the mutation on the Neurotrophic Tyrosine Kinase Receptor Type 1 (NTRK1) gene. The NTRK1 gene provides instructions for making a receptor protein that attaches to another protein called NGFβ. The NTRK1 receptor is important for the survival of nerve cells. Mutations in the NTRK1 gene lead to a protein that cannot transmit signals. In CIPA, the lack of pain sensation results from the absence of afferent neurons that are activated by tissue-damaging stimuli, whereas anhydrosis arises from the loss of innervation of eccrine sweat glands caused by sympathetic neurons.[2]

Although microcephaly is an expected finding in CIPA patients, was detected as in our case, cases with hydrocephaly have also been reported in the literature. Patients with CIPA may also present with joint dislocations, corneal ulcerations, and multiple bone fractures caused by repetitive traumas. Typical mucosal findings are the aphthous ulcers caused by repetitive traumas.[13] In CIPA, there is no specific skin symptom. Skin symptoms are often associated with anhydrosis, repetitive traumas caused by the lack of pain sensation, and self-destructive behaviors. These conditions may in turn lead to xerosis, palmoplantar hyperkeratosis, skin infections, skin ulcers, scars, and fissures. Moreover, scarring of the lips may occur as a result of circumoral dryness, leading to difficulty opening mouth.[34] The diagnosis of CIPA usually can be based on the clinical presentation, pharmacological test (intradermic reaction to 1:10,000 histamine) and neuropathological exam in electron microscopy. Detection of mutations on the NTRK1 gene represents as the last diagnostic step. There is no specific treatment method for this syndrome.[15]

This rare syndrome should be kept in mind in the infantile patients presenting with xerosis, anhydrosis, and traumatic skin lesions and genetic counseling should be provided for the families of such patients.

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Conflicts of interest

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