Keratitis-Ichthyosis-Deafness Syndrome Caused by Missense Mutation in GJB2 Encoding Connexin 26 in a Chinese Patient

Abstract

Introduction: Keratitis-ichthyosis-deafness (KID) syndrome is a rare congenital ectodermal disorder caused by a heterozygous missense mutation in GJB2 or GJB6, which encode connexin 26 and connexin 30, respectively. To date, three cases of KID syndrome caused by an N14Y mutation of GJB2 have been reported globally, but there is no relevant report in domestic literature. Case presentation: A 36-year-old man presented with scalp alopecia and absence of eyelashes, pubic hair, and axillary hair. Yellow-brown highly keratinized verrucous plaques were present on the perineum, palms, and soles. All 20 nails were severely abnormal. Keratitis, blepharitis, and profound sensorineural hearing loss were also observed. Foot biopsy revealed ichthyosis changes. Sequencing of GJB2 showed that the patient was heterozygous for a nucleotide change, c.40A > T, in exon 2, resulting in the substitution of asparagine for tyrosine at position 14 (N14Y) located in the N-terminal domain of connexin 26. Notably, the mutation site of KID syndrome has not been reported in domestic literature. The patient's father was heterozygous for the M195 V (c.583A > G) mutation, and his mother was heterozygous for the V37I (c.109G > A) mutation. The patient received oral retinoic acid, antibiotics and topical moisturizer packs, but was subsequently lost to follow-up. Discussion: KID syndrome manifests as the classic triad of chronic vascularizing keratitis, ichthyosiform erythroderma, and sensorineural hearing loss. Early and long-term multidisciplinary monitoring of affected individuals is essential. Genetic testing could help us detect the mutation site of connexin. Conclusion: These findings expand the mutation spectrum of KID syndrome in the Chinese population and provide a new understanding of the genotype–phenotype correlation. Functional studies on the N14Y mutation will help to reveal the underlying pathogenic mechanism.