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Keratitis-ichthyosis-deafness syndrome (KID) is a rare genetic disorder characterized by the triad of hyperkeratosis, ichthyosis, and congenital prelingual sensorineural deafness, with less than 100 cases described in the literature. In addition to many other extra-cutaneous manifestations, these patients are burdened by two principal increased risk factors involving the skin: the risk of developing infections and the risk of developing malignant skin tumors, especially Squamous Cell Carcinoma and Trichilemmal tumors. We present the case of a 7-year-old girl with a unique genetic variant described to date, who developed 4 dyskeratotic neoformation. Since the dermatoscopic examination was not sufficient to exclude malignancy, excisional and punch biopsies were used. Nonetheless, healing was challenging, with wound dehiscence and infection onset. Ad hoc wound care management resorting to negative pressure therapy and advanced medical honey-based dressings was necessary to achieve complete wound healing.

Background. KID syndrome (keratitis-ichthyosis-deafness) is an orphan genetic multisystem disease with autosomal recessive and dominant types of inheritance, it manifests in the neonatal period. The leading triad of symptoms is: skin lesions, ophthalmological diseases and hearing organ pathology. Clinical Case Description. Girl V., 17 years old, with KID syndrome applied to the hospital complaining on painful infiltrates of the parietal region. Multiple abscesses were lanced. Hyperkeratotic crusts were removed, unviable skin regions were excised, and abscesses' cavities were washed with antiseptic solution during daily dressings. Purulent discharge from wounds has been maintaining for 7 days. Conclusion. Where is no pathogenetic treatment for KID syndrome yet. Prevention of secondary surgical infections remains the crucial aspect in the management of such patients. Local wound treatment, symptomatic and antibacterial therapy are effective in case of skin infection.

Ichthyosis and deafness syndrome is a group of devastating genodermatoses caused by heterozygous mutations in GJB2, encoding the gap junction protein connexin 26. These syndromes are characterized by severe skin disease, hearing loss, recurrent infections, and cutaneous neoplasms. Cutaneous somatic mutations in the same gene are associated with porokeratotic eccrine ostial dermal duct nevus. Here we report a family in which a parent presented with localized epidermal nevus and his child suffered with hystrix‐like ichthyosis with deafness. Histologic examination of the parent's cutaneous lesion revealed verrucous epidermal nevus without features of porokeratotic eccrine ostial dermal duct nevus. Genetic analysis identified the same pathogenic variant, GJB2 c.148G>A (p.D50N), in DNA extracted from the parent's cutaneous lesion and the child's leukocytes, but not in the parent's leukocytes. This study expands the phenotypic heterogeneity of GJB2 mosaic variants in addition to porokeratotic eccrine ostial dermal duct nevus, and emphasizes the importance of molecular diagnosis of mosaic skin diseases considering the risk of severe inherited diseases in the offspring. [ABSTRACT FROM AUTHOR]

Objective: To determine the expression levels of connexin Cx31, Cx43 and Cx50 in the lesional skin of KID syndrome and their roles in the pathogenesis of KID syndrome. Methods: Immunohistochemistry was used to determine the expression levels of connexins Cx31, Cx43 and Cx50 in the lesional skin from both mother and son with KID syndrome. Skin samples from both an uninvolved subject of the patient’s family and normal control-unrelated to the patient’s family served as controls. Results: Expression levels of Cx31 increased in both the spinous and basal layers of the epidermis in patients, while in the controls, Cx31 only expressed in the basal layer. Expression levels and localization of Cx43 and Cx50 were comparable between the patients and the controls. Conclusion: The expression levels of Cx31 are up-regulated in patients with KID syndrome, while the expression levels of Cx43 and Cx50 are comparable between the patients and the controls.Whether these molecules are involved in the pathogenesis of KID syndrome remains to be explored.

Summary: Inherited ichthyoses are a group of genodermatoses classified as either nonsyndromic or syndromic. Nonsyndromic ichthyoses and keratitis, ichthyosis and deafness (KID) syndrome predispose to fungal infection. The diagnosis and treatment of fungal infections underlying ichthyoses are challenging. In this review, we summarize reported cases of ichthyosis with fungal infection over the past 50 years. Atypical manifestations such as alopecia, papules and brittle nails occurred in patients with ichthyosis combined with fungal infection. Various pathogenic mechanisms have been implicated, including mutations of ichthyosis‐related genes leading to disruption of the skin barrier via multiple pathways. Host immune disorders, including atopy and abnormal innate immunity also contribute to susceptibility. Specific fungi may escape the immune response. Extensive and recurrent fungal infections are not uncommon in patients with ichthyosis, making a cure more difficult and increasing the need for systemic antifungal therapy. Traditional and new ichthyosis treatments aiming to improve skin barrier function could help prevent fungal infection. In conclusion, the close relationship between ichthyosis and fungal infection is of vital importance in clinical practice and requires more attention from physicians. More studies are required to investigate the mechanisms and explore useful treatment strategies. [ABSTRACT FROM AUTHOR]

Keratitis‐ichthyosis‐deafness (KID syndrome) is a syndromes ichthyoses that is clinically and genetically heterogeneous requiring early and long‐term multidisciplinary monitoring of affected individuals. A review of the clinical, etiopathogenic and therapeutic aspects is presented of this rare congenital ectodermal disorder. [ABSTRACT FROM AUTHOR]

Verruciform xanthoma is a benign, wart‐like lesion that can clinically mimic squamous cell carcinoma. We describe two teenage patients with severe genodermatoses, recessive dystrophic epidermolysis bullosa (RDEB), and keratitis‐ichthyosis‐deafness (KID) syndrome, respectively, each found to have plaques suspicious for malignancy, later demonstrated on histopathologic examination to be verruciform xanthoma. We discuss the connection between these severe genodermatoses and the suspected pathophysiology of verruciform xanthoma. In addition, we highlight the importance of recognizing verruciform xanthoma as a clinical mimicker of squamous cell carcinoma, for which patients with RDEB and KID syndrome are at increased risk. [ABSTRACT FROM AUTHOR]

Ichthyoses are a rare group of keratinization disorders characterized by scaling of the skin due to an impaired barrier function. Few studies have addressed ear involvement in patients with ichthyosis, although it is a probably underestimated aspect of the disease. This study aims to provide an overview of the otological manifestations in ichthyosis and propose specific treatment options. Articles were collected using PubMed, EMBASE, and Web of Science. A total of 53 articles were included in this literature review. The most common ear problem in patients with ichthyosis is scale accumulation in the ear canals, which can lead to conductive hearing loss and increases the risk of ear infections. Furthermore, some types of ichthyosis are associated with outer ear malformations. Lastly, sensorineural hearing loss is common in syndromic forms of ichthyosis. Otological problems are present in all types of ichthyoses and their treatment is challenging. The involvement of ear, nose, and throat specialists in the routine care of ichthyosis patients is essential for early identification and treatment of these manifestations. More research is needed to provide more insight into the otological problems in ichthyosis and to ameliorate treatment options. • Ear problems are present in all types of ichthyosis. • Scale accumulation is the main ear problem, resulting in conductive hearing loss. • Patients have a higher prevalence of ear infections and outer ear malformations. • Sensorineural hearing loss is common in syndromic ichthyoses. • Routine care of ichthyosis patients should include involvement of ENT specialists. [ABSTRACT FROM AUTHOR]

Abstract is missing (Short communication)

A clinical case of keratitis-ichthyosis-deafness (KID syndrome) in an infant is described. The article familia-rizes pediatricians and family doctors with difficulties in the diagnosis of this rare genetic disease in infants.

Keratitis-Ichthyosis-Deafness (KID) syndrome is a congenital disorder characterized by keratitis, ichthyosis, and deafness. Authors present a 10 year old by with KID syndrome. The diagnosis was based on a clinical picture, hearing evaluations and genetic research.

Background: Keratitis-Ichthyosis-Deafness (KID) syndrome is a rare condition characterized by pre-lingual sensorineural deafness with skin hyperkeratinization. The primary cause of the disease is a loss-of-function mutation in the GJB2 gene. Mutations in Argentinean patients have not been described. Case presentation: We studied a 2 year-old boy with bilateral congenital sensorineural deafness with dry skin over the entire body, hypotrichosis of the scalp, thin and light-blond hair. Analysis of the GJB2 gene nucleotide sequence revealed the substitution of guanine-148 by adenine predicted to result in an Asp50Asn amino acid substitution. Conclusion: This is the first KID report in a patient from Argentina. This de novo mutation proved to be the cause of keratitis-ichthyosis-deafness syndrome (KID-syndrome) in the patient, and has implications in medical genetic practice. [ABSTRACT FROM AUTHOR]

Connexin mutations underlie numerous human genetic diseases. Several connexin genes have been linked to skin diseases, and mechanistic studies have indicated that a gain of abnormal channel function may be responsible for pathology. The topical accessibility of the epidermal connexins, the existence of several mouse models of human skin disease, and the ongoing identification of pharmacological inhibitors targeting connexins provide an opportunity to test new therapeutic approaches. [ABSTRACT FROM AUTHOR]

Connexins form large-pore channels that function either as dodecameric gap junctions or hexameric hemichannels to allow the regulated movement of small molecules and ions across cell membranes. Opening or closing of the channels is controlled by a variety of stimuli, and dysregulation leads to multiple diseases. An increase in the partial pressure of carbon dioxide (PCO 2) has been shown to cause connexin26 (Cx26) gap junctions to close. Here, we use cryoelectron microscopy (cryo-EM) to determine the structure of human Cx26 gap junctions under increasing levels of PCO 2. We show a correlation between the level of PCO 2 and the size of the aperture of the pore, governed by the N-terminal helices that line the pore. This indicates that CO 2 alone is sufficient to cause conformational changes in the protein. Analysis of the conformational states shows that movements at the N terminus are linked to both subunit rotation and flexing of the transmembrane helices. [Display omitted] • High-resolution cryo-EM structures of connexin26 at varying levels of PCO 2 • CO 2 alone causes conformational changes in the protein under stable pH conditions • The N-terminal helices regulate the aperture of the pore • KID syndrome mutations affecting CO 2 sensitivity map to flexion points of structure Brotherton et al. present cryo-EM structures of the connexin26 gap junction at three concentrations of CO 2. They show that at constant pH, the aperture of the pore varies depending on CO 2 concentration. Their results correlate with physiological measurements showing that elevated CO 2 closes gap junctions. [ABSTRACT FROM AUTHOR]

Background: Keratitis-Ichthyosis-Deafness (KID) syndrome (OMIM 148210) is a congenital ectodermal defect that consists of an atypical ichthyosiform erythroderma associated with congenital sensorineural deafness. KID appears to be genetically heterogeneous and most cases are caused by GJB2 mutations. Mutations in African patients have been rarely described. Case presentation: We report on two unrelated Cameroonian individuals affected with sporadic KID, presenting with the classic phenotypic triad. The two patients were heterozygous for the most frequent p.Asp50Asn mutation. This first report in patients from sub-Saharan African origin supports the hypothesis that the occurrence of KID due to p.Asp50Asn mutation in GJB2 seems not to be population specific. Conclusions: Our finding has implication in medical genetic practice, specifically in the molecular diagnosis of KID in Africans. These cases also reveal and emphasize the urgent need to develop appropriate policies to care for patients with rare/orphan diseases in Sub-Saharan Africa, as many of these cases become more and more recognizable, [ABSTRACT FROM AUTHOR]

Mutations in Connexin26 ( Cx26) give rise to a spectrum of dominantly inherited hyperproliferating skin disorders, the severest being keratitis-ichthyosis-deafness ( KID) syndrome, an inflammatory skin disorder, with patients prone to opportunistic infections. We compared the effects of peptidoglycan ( PGN) extracted from the skin commensal Staphylococcus epidermidis and the opportunistic pathogen Staphylococcus aureus on interleukin-6 and connexin expression in Ha Ca T cells (a keratinocyte cell line) and connexin channel activity in Ha Ca T and He La (connexin deficient) cells transfected to express KID and non- KID Cx26 mutations. In both cell types, PGN from S. aureus induced hemichannel activity in cells expressing KID mutants as monitored by ATP release assays following 15-min challenge, while that from S. epidermidis evoked a response in He La cells. In KID mutant expressing cells, ATP release was significantly higher than in cells transfected with wild-type Cx26. No ATP release was observed in non- KID mutant transfected cells or in the presence of carbenoxolone, a connexin channel blocker. PGN isolated from S. aureus but not S. epidermidis induced interleukin-6 and Cx26 expression in Ha Ca T cells following 6-h challenge. Challenge by PGN from S. aureus evoked a greater interleukin-6 response in cells expressing KID mutants than in cells expressing wt Cx26 or non- KID mutants. This response returned to basal levels if acute KID hemichannel signalling was blocked prior to PGN challenge. Thus, KID mutants form channels that can be triggered by the pro-inflammatory mediator PGN from opportunistic pathogens but not skin commensals, providing further insight into the genotype-phenotype relationship of Cx26 disorders. [ABSTRACT FROM AUTHOR]

Objective and importance The objective of this study was to describe long-term outcomes after cochlear implantation in keratitis-ichthyosis-deafness (KID) syndrome, often caused by GJB2 mutations, in the context of other reported cases. Clinical presentation and intervention The authors conducted correlative clinical and molecular genetic analysis on two implanted patients with KID syndrome, and tabulated their clinical outcomes. Both children had initially successful surgery. In one case, due to skin-related problems, despite extensive salvage surgery cochlear explantation was required. This patient now communicates with sign language and lip-reading. This contrasts with the outcome for the other patient whereby at post-operative year 10 he is able to easily converse by telephone. Both patients each carry a de novo 148G > A GJB2 mutation. Conclusion Patients with KID syndrome appear to be good candidates for cochlear implantation but may face significant skin-related problems which could disrupt successful post-operative habilitation. Consultation with dermatological colleagues regarding any new therapies may be warranted. [ABSTRACT FROM AUTHOR]

The article presents abstracts of poster presentations on dermatology, including topics on newborn skin disorders in a dermatology outpatient clinic in Turkey, influence of neonatal and maternal factors on the prevalence of salmon patch, and treatment of diffuse cutaneous mastocytosis with imatinib mesylate.

Abstract: KID syndrome (MIM 148210) is an ectodermal dysplasia characterized by the occurrence of localized erythematous scaly skin lesions, keratitis and severe bilateral sensorineural deafness. KID syndrome is inherited as an autosomic dominant disease, due to mutations in the gene encoding gap junction protein GJB2 (connexin 26, Cx26). Cx26 is a component of gap junction channels in the epidermis and in the stria vascularis of the cochlea. These channels play a role in the coordinated exchange of molecules and ions occurring in a wide spectrum of cellular activities. In this paper we describe two patients with Cx26 mutations cause cell death by the alteration of protein trafficking, membrane localization and probably interfering with intracellular ion concentrations. We discuss the pathogenesis of both the hearing and skin phenotypes. [Copyright &y& Elsevier]

Abstract: 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. [Copyright &y& Elsevier]

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. [ABSTRACT FROM AUTHOR]

Three children with keratitis-ichthyosis-deafness (KID) syndrome received cochlear implants at the Royal Victorian Eye and Ear Hospital. KID syndrome is a rare genodermatosis associated with mutation of the connexin-26 gene with characteristics affecting skin, hair, vision and hearing. Ichthyotic involvement of the ear canal epithelium and associated non-erosive keratosis obturans complicate hearing assessment and aid fitting. The tendency to eczematous dermatitis and otitis media is an additional problem with cochlear implantation. All cases have required additional medical management, however the outcomes show that the cochlear implant can be effective in these patients. Copyright © 2008 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Objective: To report on a 10-year-old boy with KID syndrome who presented with a new onset unilateral toe walking. Method: This patient's equinus contracture was evaluated clinically. The patient underwent to surgical lengthening of Achilles tendon. After the surgery, the patient was placed in a short-leg walking cast for 6 weeks and then received a rehabilitation programme involving stretching exercises. Results: Successful heel-to-toe gait was achieved in 3 weeks following surgery and rehabilitation. Conclusion: Surgical intervention and postsurgical rehabilitation may be indicated for children who present with toe walking attributed to contracture in the Achilles tendon. [ABSTRACT FROM AUTHOR]

Summary: Keratosis, Icthiosis, and Deafness (KID) Syndrome is a rare congenital disorder associated with dominant connexin 26 mutations, affecting epidermis, corneal epithelium, and inner ear. Given eventual visual impairment, cochlear implantation is an important consideration despite an increased risk of wound complications. We present a child with KID Syndrome and bilateral profound sensorineural hearing loss associated with a novel heterozygous missense D50A connexin 26 mutation (c.149A>C). Imaging revealed mild cochlear malformation and Dandy-Walker malformation. She received a cochlear implant at the age of 12 months, using a small incision approach. Following an immediate minor wound infection, implantation has been successful without further complication over 4 years. [Copyright &y& Elsevier]

Abstract: 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. [Copyright &y& Elsevier]