Congenital insensitivity to pain associated with PRDM12 mutation: Two case reports and a literature review

Abstract

Background: PRDM12 is a newly discovered gene responsible for congenital insensitivity to pain (CIP). Its clinical manifestations are various and not widely known. Methods: The clinical data of two infants diagnosed with CIP associated with PRDM12 mutation were collected. A literature review was performed, and the clinical characteristics of 20 cases diagnosed with a mutation of PRDM12 were summarized and analyzed. Results: Two patients had pain insensitivity, tongue and lip defects, and corneal ulcers. The genomic analysis results showed that variants of PRDM12 were detected in the two families. The case 1 patient carried heterozygous variations of c.682+1G > A and c.502C > T (p.R168C), which were inherited from her father and mother, respectively. We enrolled 22 patients diagnosed with CIP through a literature review together with our cases. There were 16 male (72.7%) and 6 female (27.3%) patients. The age of onset ranged from 6 months to 57 years. The prevalence of clinic manifestation was 14 cases with insensitivity to pain (63.6%), 19 cases with self-mutilation behaviors (86.4%), 11 cases with tongue and lip defects (50%), 5 cases with mid-facial lesions (22.7%), 6 cases with distal phalanx injury (27.3%), 11 cases of recurrent infection (50%), 3 cases (13.6%) with anhidrosis, and 5 cases (22.7%) with global developmental delay. The prevalence of ocular symptoms was 11 cases (50%) with reduced tear secretion, 6 cases (27.3%) with decreased corneal sensitivity, 7 cases (31.8%) with disappeared corneal reflexes, 5.5 cases (25%, 0.5 indicated a single eye) with corneal opacity, 5 cases (22.7%) with corneal ulceration, and 1 case (4.5%) with a corneal scar. Conclusion: The syndrome caused by PRDM12 mutation is a clinically distinct and diagnosable disease that requires joint multidisciplinary management to control the development of the disease and minimize the occurrence of complications.

Keywords: HSAN; Prdm12; corneal disease; hereditary and sensory autonomic neuropathy; insensitivity to pain; self-mutilation behavior.

FIGURE 1

Clinical manifestations of Case 1. (A) Both eyes showed conjunctival hyperemia, corneal ulceration, deep stromal infiltration, borderline ambiguity, and opacity. (B) On day 7, the corneal ulcers in both eyes gradually healed, and the conjunctival congestion was reduced. (C) On day 14, the corneal ulcers healed in both eyes. (D) On day 40, conjunctival hyperemia (−) occurred in both eyes, the corneal epithelium was intact, and corneal leukoplakia formed. (E) Tongue and lip defects and oral ulcers.

FIGURE 2

Clinical manifestations of Case 2. (A,B) Conjunctival hyperemia, corneal ulcer; (C) tongue and lip defects and oral ulcers.