Novel Variant c.148G>T of GJB2 Gene in a 5-Year-Old Child with KID Syndrome.

Dear Editor,

We read with great interest the article “KID Syndrome: a rare genodermatosis” by Vivek Kumar Dey et al. published in January 2020 on Indian Dermatology Online Journal.[1]

KID syndrome is a very rare ectodermal congenital disorder due to missense mutations in the gap junction beta-2 protein (GJB2) gene, which encodes for connexin 26 protein.[1]

Recently, a 5-year-old child was referred to our Pediatric Dermatology Unit with several clinical manifestations involving skin, tooth, eyes, and ears.

The child showed recurrent cutaneous infections, bilateral cheilitis, and diffuse irritative dermatitis. Dermatological examination showed nail dystrophies, palmo-plantar hyperkeratosis with desquamation, and erythematous hyperkeratotic plaques on extremities and trunk. The patient showed a loss of eyebrows and eyelashes, deep periocular furrows, brittle blond hair, and tooth abnormalities (hypodontia and conoid form) [Figures 1 and 2]. Psychomotor development was normal. The patient was also affected by profound bilateral congenital neurosensorial hearing loss, confirmed by audiometry, and, from 1 year of age, showed mild keratitis with photophobia.

Figure 1

Clinical manifestations of the face: deep furrows around mouth and eyes, partial loss of eyebrows, total loss of eyelashes, brittle blond hair, and tooth abnormalities (hypodontia and conoid form)

Figure 2

Nail dystrophies and palmo-plantar hyperkeratosis with desquamation

Genetic analysis of genomic DNA extracted from peripheral blood leukocytes confirmed diagnosis of KID syndrome.

A mutation analysis based on Sanger sequencing of the codubng exon of the GJB2 gene was performed, identifying a heterozygous variant NM_004004.6(GJB2):c.148G>T (p. Asp50Tyr). To date, the c.148G>T variant was never described before in patients with KID syndrome[2] and is absent in the general population (gnomAD).

Familial history of genetic diseases was negative and the parents have not been tested.

From birth, the patient used topical treatments with emollients, urea, other keratolytic products or topical antibiotics.

She is regularly followed by a multispeciality team, including dermatologists, otorhinolaryngologists, ophthalmologists, and speech therapists.

The three markers of KID syndrome are keratitis, deafness, and ichthyosis. KID syndrome is clinically characterized by neurosensorial hearing loss, hyperkeratosis of the palms, soles, and skin folds, widespread alopecia of the scalp, partial loss of the eyebrows, nail dystrophy, and dentition anomalies.[34] The etiopathogenesis of KID syndrome is due to missense mutation of the GJB2 gene, which encodes for the connexin 26 protein, involved in the development of intercellular channels of ectodermal-derived several epithelia.[25] This mutation leads to dysregulation in the epidermal calcium homeostasis, increasing proliferation, and aberrant cell differentiation. The consequence is the abnormal lipid composition of the stratum corneum, with a lack of ceramides and barrier defect, compensated by hyperproliferation of stratum basale, determining the typical hyperkeratosis.[5]

In patients with suspected KID syndrome, clinicians should perform, if possible, molecular genetic testing in order to achieve the correct diagnosis and to identify the specific syndrome among the heterogeneous group of ectodermal dysplasias with possible correlations genotype-phenotype.

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