Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022568 (keratitis)
 5,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recently, a number of medications approved for nondermatologic use have proved useful against dermatologic diseases. This article reviews the dermatologic uses and effects of deferasirox, bortezomib, dasatinib, and cyclosporine eye drops. Deferasirox--an oral iron chelator--could be an effective treatment against porphyria cutanea tarda, hemochromatosis, and pathogens such as mucor that thrive in iron rich environments. Bortezomib, a proteasome inhibitor and multiple myeloma treatment, may be effective against nodular amyloid and has been effectively used against squamous cell carcinoma; although trials demonstrate it is ineffective against metastatic melanoma. Bortezomib has many cutaneous side effects including erythematous plaques or nodules, a generalized morbilliform erythema with ulcerations and fever, purpuric eruptions, leukocytoclastic vasculitis, Sweet's syndrome, and folliculitis. Dasatinib is a multi-targeted tyrosine kinase inhibitor active in vitro against most cell lines containing BCR-ABL mutations that confer resistance to imatinib. Dasatinib is likely to be effective against dermatofibroma sarcoma protuberans and cutaneous acute lymphoblastic leukemia, and has caused panniculitis. Cyclosporine 0.05% ocular emulsion (eye drops) are approved to treat dry eyes including dry eyes caused by collagen vascular disease. Cyclosporine eye drops might also have utility in treating eye pathology of ocular rosacea, atopic keratoconjunctivitis, graft versus host disease, herpes keratitis, chronic sarcoidosis of the conjunctiva, conjunctival manifestations of actinic prurigo, keratitis of keratitis-ichthyosis deafness (KID) syndrome, and lichen planus-related kerato-conjunctivitis. This article speculates that cyclosporine eye drops would also be useful for any disease causing ectropion or eclabion of the eye as well as toxic epidermal necrolysis-related eye pathology (in particular corneal scarring).
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PMID:A review of deferasirox, bortezomib, dasatinib, and cyclosporine eye drops: possible uses and known side effects in cutaneous medicine. 1737 1

A 26-year-old Japanese woman was referred to our hospital with generalized hyperkeratosis associated with keratitis and a hearing defect. The patient was born from nonconsanguineous parents. Her skin was moderately hyperkeratotic at birth. During childhood, the thickness of the skin increased progressively. Bilateral sensorineural deafness was recognized at the age of 3 years. Visual disturbance was noted in later childhood, and corneal transplantations to the right eye were performed twice at the age of 16 and 25 years, but did not improve her visual acuity. There was no family history of similar disease. On physical examination, the patient showed erythematous, keratotic, scaly plaques on the cheeks, auricles, and perioral area (Fig. 1a). A grainy, spiculated, hyperkeratotic papillomatosis was particularly marked on the palms and the edge of the feet (Fig. 1b,c). The nails were slight hypertrophic, but not dystrophic. Ophthalmologic examination revealed the loss of eyebrows and eyelashes and hyperkeratotic lesions of the eyelids (Fig. 1d). Corneal opacification was observed in the right eye. Conjunctivitis and blepharitis with photophobia were also observed in both eyes (Fig. 1d,e). A skin biopsy specimen from the right lower thigh showed basket-wave hyperkeratosis and papillomatosis of the epidermis. Hyperkeratotic plugs were not observed (Fig. 1f). Laboratory data, including complete blood cell count, sedimentation rate, immunoglobulins and transaminases, urea, cholesterol, and triglycerides were normal. With informed consent, genomic DNA was extracted from blood samples. The complete open reading frame of the GJB2 gene was polymerase chain reaction amplified and sequenced. A transition mutation (148G --> A) was detected, resulting in a putative amino acid change from aspartic acid to asparagine at codon 50 (Fig. 2). The mutation was not present in her parents or two siblings. These clinical, pathologic, and genetic data supported the diagnosis of keratitis-ichthyosis-deafness syndrome.
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PMID:A case of keratitis-ichthyosis-deafness (KID) syndrome. 1744 83

One case of keratitis ichthyosis deafness (KID) syndrome and two cases of bullous ichthyosiform erythroderma (BIE) were treated with systemic acitretin. The severe hyperkeratotic lesions improved dramatically with acitretin therapy in the KID case. Substantial improvement of the palmoplantar keratoderma was also observed. During follow-up, laboratory results remained within normal limits and no skeletal abnormalities were detected. The two cases with BIE also showed good responses to acitretin. Long-term follow-up of these cases showed that signs and symptoms were well under control and no adverse effects were noted.
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PMID:Severe ichthyosis-related disorders in children: response to acitretin. 1752 Apr 71

Keratitis-Ichthyosis-Deafness (KID) syndrome (OMIM 148210) is a congenital ectodermal defect. KID consists of an atypical ichthyosiform erythroderma associated with congenital sensorineural deafness. A rare form of the KID syndrome is a fatal course in the first year of life due to severe skin lesion infections and septicaemia. KID appears to be genetically heterogeneous and may be caused by mutations in connexin 26 or connexin 30 genes. GJB2 mutations in the connexin 26 gene are the main cause of the disease. Most of the cases caused by GJB2 mutations are sporadic, but dominant transmission has also been described. To date, the rare lethal form of the disease has been only observed in two Caucasian sporadic patients with the GJB2 mutation, with the p.Gly45Glu (G45E) arising de novo. We have reported an African family with dizygotic twins suffering from a lethal form of KID. The dizygosity of the twins was confirmed by microsatellite markers. The two patients were heterozygous for the G45E mutation of GJB2, whereas the mutation was not detected in the two parents. The unusual transmission of the disease observed in this family could be explained by the occurrence of a somatic or more probably a germinal mosaic in one of the parents.
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PMID:A familial case of Keratitis-Ichthyosis-Deafness (KID) syndrome with the GJB2 mutation G45E. 1802 54

KID syndrome is a rare congenital disorder characterized by keratitis, ichthyosis, and deafness. We have described a 4-year-old girl who is treated with bland emollients and topical keratolytics such as urea and surprisingly observed marked improvement in skin hyperkeratosis and palmoplantar keratoderma. We think that along with urgent ophthalmologic and otolaryngologic measures, simple topical therapies may improve skin condition in KID syndrome precluding the possible hazards of systemic retinoid therapy.
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PMID:KID syndrome. 1831 8

Keratitis ichthyosis deafness syndrome is a rare congenital ectodermal disorder. It appears to be genetically heterogeneous and may be caused by mutations in the connexin 26 (Cx26) gene (GJB2) or in the connexin 30 gene. It is characterized by the association of ichthyosis-like skin lesions, hearing loss, and vascularizing keratitis. We report the clinical and molecular findings in a 5-year-old girl with keratitis ichthyosis deafness syndrome. DNA sequencing in our patient revealed a p.Ser17Phe mutation in GJB2. Besides the typical clinical features of keratitis ichthyosis deafness syndrome, a peculiar intriguing finding not previously described in the literature in this condition was that polarizing light microscopy of the scalp hair in our patient revealed striking bright and dark bands as seen in trichothiodystrophy. Amino acid analysis of the hair sample also disclosed a reduced cysteine index. We emphasize that it would be of great benefit to examine hair shafts in other patients with keratitis ichthyosis deafness syndrome for trichothiodystrophy-like abnormalities.
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PMID:Trichothiodystrophy-like hair abnormalities in a child with keratitis ichthyosis deafness syndrome. 1878 90

The connexins are a family of proteins whose major function is as part of the gap junctions of cell-to-cell channels. They are expressed in several tissues including brain, skin, and cochlea. Mutations in connexin genes play a major role in non-syndromic sensorineural deafness, but have been also described in individuals with variable dermatological features. In recent years, many genes responsible for hereditary skin diseases have been discovered. These genes may encode different proteins that participate in the terminal differentiation of the epidermis. Therefore alteration or absence of these proteins causes a keratinization disorder. It has been demonstrated that distinct germline mutations within six connexin (Cx) genes GJB2 (Cx26), GJB6 (Cx30), GJB3 (Cx31), GJA1 (Cx43), GJB4 (Cx30.3), and GJB5 (Cx31.1), may cause sensorineural hearing loss and various skin disease phenotypes. The crucial functional importance of each of these connexins in the mentioned ectodermic tissues is reflected by the finding that genetic defects in their genes produce a wide spectrum of genetic disorders comprising sensorineural hearing loss, disorders of cornification of the skin, hair, and nails, and keratitis. Here, we report on different mutations in the connexin genes in individuals with or without hearing loss and different skin disorders illustrating the clinical and genetic heterogeneity of the condition.
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PMID:Connexin mutations in Brazilian patients with skin disorders with or without hearing loss. 1928 57

The Keratitis-Ichthyosis-Deafness syndrome (KIDS) is an autosomal dominant ectodermal dysplasia characterized by ocular, skin, and ear anomalies, including keratitis, palmoplantar keratoderma, and congenital hearing loss. Most cases are due to mutations in the GJB2 gene encoding connexin 26. The Dandy-Walker malformation (DWM) is a developmental anomaly of the midline of the cerebellum with complete or partial agenesis of the vermis and cystic dilatation of the fourth ventricle. The association of KID syndrome with DWM has been reported a few times, but thought to be coincidental. We report 4 additional patients with KIDS and DWM, supporting the possibility that this is an association and not a coincidental finding. This also suggests that the GJB2 gene may have a role in other cases with DWM of, as yet, unknown etiology.
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PMID:Dandy-Walker malformation in patients with KID syndrome associated with a heterozygote mutation (p.Asp50Asn) in the GJB2 gene encoding connexin 26. 1979 13

Gap junctions allow the exchange of ions and small molecules between adjacent cells through intercellular channels formed by connexin proteins, which can also form functional hemichannels in nonjunctional membranes. Mutations in connexin genes cause a variety of human diseases. For example, mutations in GJB2, the gene encoding connexin-26 (Cx26), are not only a major cause of nonsyndromic deafness, but also cause syndromic deafness associated with skin disorders such as palmoplantar keratoderma, keratitis-ichthyosis deafness syndrome, Vohwinkel syndrome, hystrix-ichthyosis deafness syndrome and Bart-Pumphrey syndrome. The most common mutation in the Cx26 gene linked to nonsyndromic deafness is 35DeltaG, a frameshift mutation leading to an early stop codon. The large number of deaf individuals homozygous for 35DeltaG do not develop skin disease. Similarly, there is abundant experimental evidence to suggest that other Cx26 loss-of-function mutations cause deafness, but not skin disease. By contrast, Cx26 mutations that cause both skin diseases and deafness are all single amino acid changes. Since nonsyndromic deafness is predominantly a loss-of-function disorder, it follows that the syndromic mutants must show an alteration, or gain, of function to cause skin disease. Here, we summarise the functional consequences and clinical phenotypes resulting from Cx26 mutations that cause deafness and skin disease.
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PMID:Connexin-26 mutations in deafness and skin disease. 1993

The autosomic dominant KID Syndrome (MIM 148210), due to mutations in GJB2 (connexin 26, Cx26), is an ectodermal dysplasia with erythematous scaly skin lesions, keratitis and severe bilateral sensorineural deafness. The Cx26 protein is a component of gap junction channels in epithelia, including the cochlea, which coordinates the exchange of molecules and ions. Here, we demonstrate that different Cx26 mutants (Cx26D50N and Cx26G11E) cause cell death in vitro by the alteration of intra-cellular calcium concentrations. These results help to explain the pathogenesis of both the hearing and skin phenotypes, since calcium is also a potent regulator of the epidermal differentiation process.
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PMID:Connexin 26 (GJB2) mutations, causing KID Syndrome, are associated with cell death due to calcium gating deregulation. 2023 Jul 88


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