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Less than 100 cases have been described so far.

Patients usually present at birth with generalized erythema and ichthyosiform scaling. The skin manifestations are progressive with erythrokeratoderma characterized by well-demarcated erythematous and keratotic plaques with a verrucous appearance predominantly located on the face, scalp, ears, elbows and knees. Other skin changes include deep furrows around the mouth, palmoplantar hyperkeratosis (PPHK) with leather grain-like keratoderma, follicular HK on the trunk, and spiky HK (hystrix-like ichthyosis) in some cases. The skin lesions are prone to infection and rare fatal cases of severe recurrent infections with septicemia have been reported. Nail dystrophy, alopecia, and sparse or absent eyebrows and eyelashes are also frequent. KID/HID patients have an increased susceptibility for squamous cell and tongue carcinomas. Hearing loss is congenital, usually sensorineural and is often profound. Ocular findings may be absent in some patients but when present onset usually occurs during childhood or adolescence with photophobia, punctate keratitis and progressive corneal vascularization leading to vision loss. The combined vision and hearing loss may lead to severe developmental delay. Cerebellar and neuromuscular defects have been reported in a few cases.

KID/HID syndrome is caused by mutations involving the N-terminus and first extracellular loop of the GJB2 gene (13q11-q12), encoding connexin-26. One patient with KID and atrichia had a mutation in the GJB6 gene (13q12) encoding connexin-30.

Diagnosis is suspected on the basis of dermatological, ophthalmological and hearing evaluation. Histological findings are nonspecific, revealing acanthosis and orthokeratotic HK. MRI may also be indicated to detect cerebellar anomalies. The diagnosis may be confirmed by molecular analysis.

Differential diagnoses should include diseases belonging to the erythrokeratoderma group, as well as Clouston syndrome and keratosis follicularis spinulosa decalvans.

Prenatal diagnosis may be offered to families of an index case (generalized form or mosaicism) in which the disease-causing mutation has been identified.

Most of the reported cases were sporadic, but familial cases with autosomal dominant inheritance have been reported. A few cases of KID syndrome caused by parental germline mosaicism for the GJB2 gene have also been described. Genetic counseling should be proposed to affected families as the risk of transmission from an affected parent is 50%. Segmental skin lesions may correspond to somatic and germline mosaicism, and should be considered as a risk factor for transmission of a generalized form.

Management is symptomatic only. The use of systemic retinoids is controversial in patients with KID/HID and several authors have recommended limiting the treatment of the skin manifestations to application of topical therapies (bland emollients and topical keratolytics). KID/HID patients should undergo regular surveillance for mucosal carcinomas. Careful ophthalmological and ORL follow-up should be recommended and patients should be included in developmental programs for combined hearing and vision loss. Cochlear implants have been shown to be beneficial in some cases.

The prognosis for patients with KID/HID syndrome is variable and, although cases with a fatal outcome are rare, the cutaneous manifestations persist and are generally severe with recurrent infections and an increased risk of mucosal carcinomas. The combined hearing and vision loss may lead to significant developmental delay.

Last update: April 2009 - Expert reviewer(s): Pr Alain HOVNANIAN