title: Phenotypic variability in gap junction syndromic skin disorders: experience from KID and Clouston syndromes' clinical diagnostics.
abstract: Connexins belong to the family of gap junction proteins which enable direct cell-to-cell communication by forming channels in adjacent cells. Mutations in connexin genes cause a variety of human diseases and, in a few cases, result in skin disorders. There are significant differences in the clinical picture of two rare autosomal dominant syndromes: keratitis-ichthyosis-deafness (KID) syndrome and hidrotic ectodermal dysplasia (Clouston syndrome), which are caused by GJB2 and GJB6 mutations, respectively. This is despite the fact that, in both cases, malfunctioning of the same family proteins and some overlapping clinical features (nail dystrophy, hair loss, and palmoplantar keratoderma) is observed. KID syndrome is characterized by progressive vascularizing keratitis, ichthyosiform erythrokeratoderma, and neurosensory hearing loss, whereas Clouston syndrome is characterized by nail dystrophy, hypotrichosis, and palmoplantar keratoderma. The present paper presents a Polish patient with sporadic KID syndrome caused by the mutation of p.Asp50Asn in GJB2. The patient encountered difficulties in obtaining a correct diagnosis. The other case presented is that of a family with Clouston syndrome (caused by p.Gly11Arg mutation in GJB6), who are the first reported patients of Polish origin suffering from this disorder. Phenotype diversity among patients with the same genotypes reported to date is also summarized. The conclusion is that proper diagnosis of these syndromes is still challenging and should always be followed by molecular verification.
authors.affiliation: Department of Medical Genetics, The Institute of Mother and Child, ul.Kasprzaka 17a, 01-211, Warsaw, Poland, anna.kutkowska@imid.med.pl.
authors.forename: Anna
authors.initials: A
authors.lastname: Kutkowska-Kaźmierczak
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Niepokój
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Wertheim-Tysarowska
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Giza
authors.forename: Maria
authors.initials: M
authors.lastname: Mordasewicz-Goliszewska
authors.forename: Jerzy
authors.initials: J
authors.lastname: Bal
authors.forename: Ewa
authors.initials: E
authors.lastname: Obersztyn
mesh_terms: D000328:Adult; D002675:Child, Preschool; D000072259:Connexin 26; D000075302:Connexin 30; D017630:Connexins / Q000235:genetics*; D004252:DNA Mutational Analysis; D004476:Ectodermal Dysplasia / Q000235:genetics*; D005260:Female; D017629:Gap Junctions / Q000235:genetics*; D006801:Humans; D007223:Infant; D007634:Keratitis / Q000235:genetics; D008297:Male; D010375:Pedigree; D010641:Phenotype; D011044:Poland
chemical_list: D000075302:Connexin 30; D017630:Connexins; C000607042:GJB2 protein, human; C491020:GJB6 protein, human; D000072259:Connexin 26