ABSTRACT
Collodion baby is a congenital, transient phenotype encountered in approximately 70-90% of autosomal recessive congenital ichthyosis and is an important entity of neonatal erythroderma. The clinical outcome after this severe condition is variable. Genetic mutations of components of the epidermal lipoxygenase pathway have been implicated in the majority of self-improving collodion ichthyosis (SICI). In SICI, the shedding of the collodion membrane reveals clear skin or only mild residual manifestation of ichthyosis. Here we report the case of a girl born with a severe form of collodion baby phenotype, whose skin almost completely cleared within the first month of life. At the age of 3 years, only mild symptoms of a keratinization disorder remained. However, the severity of erythema and scaling showed mild fluctuations over time. To objectively evaluate the skin changes of the patient, we assessed the ichthyosis severity index. Upon sequencing of the ALOX12B gene, we identified a previously unreported heterozygous nonsense mutation, c.1607G>A (p.Trp536Ter) with the recurrent, heterozygous mutation c.1562A>G (p.Tyr521Cys). Thereby, our findings expand the genotypic spectrum of SICI. In addition, we summarize the spectrum of further genetic diseases that can present at birth as collodion baby, in particular the SICI.
ABSTRACT
Keratins are one of the main fluorophores of the skin. Keratinization disorders can lead to alterations in the optical properties of the skin. We set out to investigate a rare form of keratinopathic ichthyosis caused by KRT1 mutation with two different optical imaging methods. We used a newly developed light emitting diode (LED) based device to analyze autofluorescence signal at 405 nm excitation and diffuse reflectance at 526 nm in vivo. Mean autofluorescence intensity of the hyperkeratotic palmar skin was markedly higher in comparison to the healthy control (162.35 vs. 51.14). To further assess the skin status, we examined samples from affected skin areas ex vivo by nonlinear optical microscopy. Two-photon excited fluorescence and second-harmonic generation can visualize epidermal keratin and dermal collagen, respectively. We were able to visualize the structure of the epidermis and other skin changes caused by abnormal keratin formation. Taken together, we were able to show that such imaging modalities are useful for the diagnosis and follow-up of keratinopathic diseases.
Subject(s)
Hyperkeratosis, Epidermolytic , Keratins , Child, Preschool , Humans , Male , Nonlinear Optical Microscopy , Optical Imaging , SkinABSTRACT
Mutations in genes keratin 5 (KRT5) and 14 (KRT14) encoding the basal type keratin intermediate filaments have been identified in epidermolysis bullosa simplex (EBS) families and are likely to cause skin fragility. Three novel keratin 14 mutations in cases from the Hungarian Epidermolysis Bullosa Centre are reported. In a 7-year-old boy with Dowling-Meara type EBS (DM-EBS), who had severe skin symptoms with extended herpetiform blisters, a novel amino acid substitution N123K in keratin 14 had been detected. A 26-year-old woman with mild DM-EBS with prominent palmoplantar hyperkeratosis and without active blister formation had a novel R125G mutation in keratin 14. In a 6-year-old girl, with Weber-Cockayne type EBS (WC-EBS) with palmoplantar blisters and moderate mental retardation, a novel V133L substitution was detected. Her pedigree showed autosomal dominant mode of inheritance; in the two other families, only the index patients were affected. The N123K and R125G mutations causing DM-EBS phenotypes are located within the helix initiation motif of the rod domain, whereas the very close V133L mutation underlying the WC-EBS phenotype is outside of this region. These novel amino acid substitutions provide further information for genotype-phenotype correlation in KRT14 mutations, and demonstrate the first molecular genetic data in EBS patients from Hungary.
