|Disease group||Keratinization disorders|
|DISEASE NAME||KERATITIS-ICHTHYOSIS-DEAFNESS SYNDROME|
|Gene (s)||GJB2 (604418), GJB6 (604418)|
KID is a rare autosomal dominant keratinization disorder mainly characterized by keratitis, progressive erythrokeratoderma and profound sensorineural deafness.
The skin is thickened with a coarse-grained aspect. Patients develop well-circumscribed erythematous and hyperkeratotic plaques on the face and the limbs, often symmetrically distributed, widespread in severely cases. Palmoplantar keratoderma with a grainy leather-like surface is constant. Patients often have an elderly facies with deep grooves. Hyperplastic inflammatory nodules can be present. Other features include sparse or absent hairs, eyelashes, and eyebrows, nail and teeth dystrophy, heat intolerance. Sensorineural hearing loss is congenital and generally profound and bilateral. Vascularizing keratitis develops during infancy and childhood and results in notable visual impairment.
Recurrent blepharoconjunctivitis, corneal ulcerations and pannus participate in causing progressive and severe visual impairment. Photophobia is frequent. Skin and eye anomalies usually worsen with time. Patients have an increased susceptibility to mucocutaneous infections. Squamous cell carcinoma of the skin and tongue have been reported in several cases.
KID is caused by missense mutations in the connexin-26 (Cx26) gene (GJB2) in the majority of cases. A common GJB2 recurrent mutation (p.D50N) accounts for more than 80% of reported cases. One case was found to be caused by a mutation in the GBJ6 gene encoding connexin 30 (Cx30). Connexins form gap junction channels that allow the diffusional exchange of ions and small metabolites between cells.
These mutations lead to functional impairment of the gap junction system. The mechanisms whereby GJB2 mutations lead to abnormal epidermal differentiation, decreased host defense and increased carcinogenic potential remain unclear.
The diagnosis of KID syndrome is established by clinical examination. Histological study of skin abnormalities is not specific.
Molecular genetic testing: Sequence analysis of the GBJ2 gene identifies a common p.D50N missense mutation in more than 80 % of cases. Other rare GBJ2 mutations include G12R, S17F, G45E, D50Y. A mutation in GJB6 has also been identified (p.V37E)c. A majority of cases are sporadic.
Prenatal testing may be available for families in which the disease mutation has been identified, and in which the course of the disease in affected members has been of particular severity.
Surveillance for development of skin and mucosal malignancy is important. Antiseptic baths, intermittent antibiotic therapy and systemic antifungal agents (oral ketoconazole or fluconazole) should be used to control and treat infections. Keratolytics and emollients are usually not sufficient to treat hyperkeratosis. Systemic retinoids can improve the keratoderma but expose to the risk of exacerbating the keratitis. Careful and frequent eye and hearing evaluation and follow-up are essential. Corneal transplants for advanced keratitis has usually failed. Hearing aids, cochlear implants, speech therapy and appropriate educational context will improve the outcome.