The Comèl-Netherton syndrome is an autosomal recessive multisystemic disorder characterized by localized or generalized congenital ichthyosis, hair shaft abnormalities, immune deficiency, and markedly elevated IgE levels. Life-threatening complications during infancy include temperature and electrolyte imbalance, recurrent infections, and failure to thrive. To study the clinical presentations of the Comèl-Netherton syndrome and its molecular cause, we ascertained 19 unrelated families of various ethnic backgrounds. Results of initial linkage studies mapped the Comèl-Netherton syndrome in 12 multiplex families to a 12 cM interval on 5q32, thus confirming genetic homogeneity of Comèl-Netherton syndrome across families of different origins. The Comèl-Netherton syndrome region harbors the SPINK5 gene, which encodes a multidomain serine protease inhibitor (LEKTI) predominantly expressed in epithelial and lymphoid tissues. Recently, recessive mutations in SPINK5 were identified in several Comèl-Netherton syndrome patients from consanguineous families. We used heteroduplex analysis followed by direct DNA sequencing to screen all 33 exons and flanking intronic sequences of SPINK5 in the affected individuals of our cohort. Mutation analysis revealed 17 distinct mutations, 15 of which were novel, segregating in 14 Comèl-Netherton syndrome families. The nucleotide changes included four non-sense mutations, eight small deletions or insertions leading to frameshift, and five splice site defects, all of which are expected to result in premature terminated or altered translation of SPINK5. Almost half of the mutations clustered between exons 2 and 8, including two recurrent mutations. Genotype-phenotype correlations suggested that homozygous nucleotide changes resulting in early truncation of LEKT1 are associated with a severe phenotype. For the first time, we used molecular data to perform prenatal testing, thus demonstrating the feasibility of molecular diagnosis in the Comèl-Netherton syndrome.

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Infants wearing breathable disposable diapers experienced significantly less diaper dermatitis (DD) compared to infants wearing standard, nonbreathable disposable diapers in a series of double-blind clinical trials. Severe DD, including confirmed infection with Candida albicans, was reduced by 38-50% among infants wearing highly breathable (HB) diapers. The prevalence of DD was inversely related to the breathability of the garments. The inhibitory effect of breathable diapers on the survival of Candida was further confirmed in controlled experiments with adult volunteers. A suspension of C. albicans cells was applied to delineated sites on the volar forearm. Each site was then covered by a full-thickness patch from either an HB or a standard diaper. Survival of Candida colonies was reduced by almost two-thirds in the breathable diaper-covered sites compared to the control sites.

Mendelian disorders of cornification (ichthyosis; MeDOC) often present in the neonatal period with little warning to providers or parents. This report reviews the majority of ichthyoses with congenital findings. The neonatal presentation of many MeDOC often differs from the later phenotype because of the changes in the skin that occur with transition from an intrauterine to extrauterine environment. While differentiation of ichthyosis subtypes in the neonatal period is difficult, there are certain phenotypic groups within which these neonates fall, recognition of which can guide initial work up and treatment. For this report, these are categorized as: exuberant vernix; collodion baby/harlequin ichthyosis (HI); ichthyosiform erythroderma; blistering; and normal skin/xerosis phenotypes.