Keratitis, ichthyosis, and deafness (KID) syndrome in half sibs.
ABSTRACT The keratitis, ichthyosis, and deafness (KID) syndrome is a rare congenital disorder of the ectoderm characterized by diffuse hyperkeratotic erythroderma, keratitis with neovascularization of the cornea, and severe neurosensory hearing loss. A familial occurrence of this syndrome has been mentioned in four reports including three of vertical transmission and one of two affected sisters born from consanguineous, unaffected parents. We report for the first time a familial case of KID syndrome in two half siblings born to the same unaffected mother. This new observation allows us to propose various hypotheses about its mode of inheritance.
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ABSTRACT: Keratitis, ichthyosis, and deafness (KID) syndrome is a rare genodermatosis associated with mutations in the connexin 26 gene. Although characterized by this clinical triad, KID syndrome predisposes to a heterogeneous spectrum of cutaneous manifestations and complications, both infectious and neoplastic in nature. Chronic mucocutaneous candidiasis and/or superinfection of skin lesions commonly occur and warrant aggressive therapeutic intervention. Benign neoplasms, namely trichilemmal tumors, have also been reported and can herald malignant growth and invasive disease. Squamous cell carcinoma of both mucosa and skin, especially acral sites, occurs in approximately 15% of patients. The pathogenesis of KID syndrome can be at least partially explained by the role of connexin 26 in intercellular communication and carcinogenesis, but the precise mechanism of disease remains unclear. Treatment strategies, which have ranged from antifungals and antibiotics to systemic retinoids, pose an ongoing challenge given the spectrum of disease. A review of the literature, with a particular focus on infection and malignancy associated with KID syndrome, and updates on the pathogenesis of disease, is discussed.Journal of the American Academy of Dermatology 02/2013; · 5.00 Impact Factor
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ABSTRACT: The combination of pre-lingual and sensorinerual deafness with skin hyperkeratinization is a relatively rare pathology. Only 11 families affected by this disorder were described in the literature during the last 30 years (from 1975 to 2002). To date, there are no more than 50 cases of this condition known in the world. Modern molecular methods revealed in all such patients a mutation in the GJB2 gene as the primary cause of the disease. We studied a 4 year-old girl with bilateral congenital grade IV sensorineural deafness. Her unusual appearance drew attention aas early as the primary examination; the patient had the deep-set eyes and dry skin over the entire body, she presented with hypotrichosis of the scalp, thin and light-blond hair. Analysis of the nucleotide sequence of the GJB2 gene revealed the substitution of guanine-148 by adenine that led to D50N amino acid substitution. This dominant mutation proved to be the cause of keratitis-ichthyosis-deafness syndrome (KID-syndrome). A review of the literature concerning molecular diagnostics and clinical features of this syndrome is presented. The results of molecular-genetic investigations provided the data on pathogenesis of different variants of sensorineural deafness and the associated genotype-phenotype relationships that may be used as a basis for the further development of the methods for the prevention and treatment of KID-syndrome.Vestnik otorinolaringologii 01/2012;
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ABSTRACT: The term inherited disorders of keratinization encompasses a number of genetic skin disorders linked by the common finding of abnormal epidermal differentiation, often with aberrant formation of the cornified envelope (cornification). These disorders, such as ichthyoses, palmoplantar keratodermas, and erythrokeratodermas, have been classified traditionally on the basis of clinical morphology and the presence or absence of extracutaneous manifestations. In many cases the features do not facilitate easy segregation into a single distinct and well-defined group (eg, palmoplantar keratoderma and ichthyosis coexist in a number of conditions). These inherited disorders of keratinization may also feature epidermal fragility. Clinical, histologic, and ultrastructural morphologic characteristics of these conditions have been used to further classify and subdivide them. As none of these diseases is common, the morphologic approach has great benefit to the practicing clinician and offers a logical pathway to diagnosis when confronted with a patient for the first time in the clinic. Advances in genetic technology during the past 10 years have led to an enormous increase in understanding the basic molecular defects responsible for inherited disorders of keratinization, and these advances have made possible a new, molecular mechanism-based approach to their classification that complements the morphologic system. In the great majority of cases recent molecular insights have confirmed the accuracy of the original clinical distinctions and stand as testimony to the skilled and detailed observations made by generations of clinicians. As knowledge increases, however, the association of mutations in one gene with a distinct phenotype has become more complex. For example, clinically distinct conditions have been attributed to different mutations in the KRT1 gene (clinical heterogeneity). A further example of clinical heterogeneity is the spectrum of phenotypes attributable to mutations in the gene that encodes desmoplakin 1; dominantly acting mutations cause a skin-limited phenotype, but recessively acting mutations may cause a dilated cardiomyopathy and hair phenotype in addition to epidermal changes. In others, identical clinical phenotypes have been attributed to mutations in several genes (genetic heterogeneity), for example, with lamellar ichthyosis, in which 4 gene loci in addition to that encoding transglutaminase 1 have been identified. A sound knowledge of these issues is vital to the clinician involved in the care of patients with inherited disorders of keratinization. The direct benefits to patients of this increased knowledge are improved diagnostic certainty, an understanding of the biology underlying the gene defect, and more accurate genetic counseling. It is likely that this increased understanding will lead to the development of more rational treatments for many of these distressing conditions in the near future. Attempts at gene therapy have been limited to date, but ex vivo gene correction has succeeded for both lamellar ichthyosis and recessive X-linked ichthyosis in mouse models. (Curr Probl Dermatol 2002;14:71-116)Current Problems in Dermatology 05/2002; 14(3):77–115.