Filaggrin mutations and the skin.

Filaggrin is very important in the terminal differentiation of the skin and the formation of cornified envelope in the stratum corneum. Several mutations in the filaggrin gene have been identified in the last decade, mostly from the European countries. Loss of function mutations in the filaggrin gene results in reduced production of filaggrin, depending on the type and site of mutation. Such mutations in the filaggrin gene have been shown to be the most significant genetic risk factor for development of atopic dermatitis and undoubtedly has a role in the pathogenesis of ichthyosis vulgaris. Though there is theoretical possibility of association with hand eczema and allergic contact dermatitis; in clinical studies, the strength of these associations was not significantly strong. In this review, we have discussed the structure and function of filaggrin, basic genetics, type of mutations in filaggrin gene, and association of such mutations with different dermatoses.

Peeling skin syndrome in eight cases of four different families from India and Bangladesh.

Peeling skin syndrome (PSS) is a rare recessively inherited ichthyosiform genodermatoses characterized by superficial skin peeling. This has 2 subtypes, acral (APSS; OMIM 609796) and generalized form (OMIM 270300). The later has been subdivided into type A (non-inflammatory) and type B (inflammatory). Eight cases of peeling skin syndrome in 4 families were recorded over a period of 5 years. They were diagnosed clinically and confirmed histopathologically. Disease onset ranged from birth to childhood age (mean 5.25 ± 4.528 years) and age at presentation ranged from 7-35 years (mean 23.25 ± 10.471 years). Males outnumbered females (M:F - 5:3). All had non-inflammatory generalized disease of type-A PSS variety, except one who had type-B PSS. Two Muslim families (1 st and 2 nd family, total 5 patients) came from nearby country Bangladesh, and the 2 Hindu families were Indian. Higher severity over acral areas in generalized type, possible autosomal dominant pattern of inheritance and improvement with age as found in this series were new manifestations and possibly unreported previously. The disease was found to be poorly responsive to oral retinoids. Prevalence of the disease may be higher than expected. Importance of mutational analysis was also highlighted.

A family of Bart-Pumphrey syndrome.

Bart-Pumphrey syndrome (BPS) is an autosomal-dominant disorder characterized by hearing loss, leukonychia, knuckle pads and palmoplantar keratoderma. Two mutations in the extracellular domain of GBJ2 are resposible for this syndrome. To date, less than 10 case reports or clinical series about BPS have been published in the literature. Hearing loss and knuckle pads are the more commonly seen findings of this syndrome. Three generations and six family members with variable findings of knuckle pads, leukonychia, hearing loss and palmoplantar hyperkeratosis were presented in this report. We want to emphasize that dermatogists must be alert during the evaluation of these findings because some findings of this disorder may be vague or absent.

Tuberous sclerosis complex associated with dyschromatosis universalis hereditaria.

Tuberous sclerosis is an autosomal dominant disease due to mutations in two genetic loci, characterized by hamartoma formation in the skin, nervous system, heart, kidney and other organs. Dyschromatosis universalis hereditaria is an autosomal dominant genodermatosis, characterized by small hyperpigmented and hypopigmented macules, uniformly distributed over the entire body. The face is rarely involved and the palms, soles and mucous membranes are usually spared. We report a case of tuberous sclerosis with dyschromatosis universalis hereditaria, with hyperpigmented and hypopigmented macules affecting the palms, soles and oral mucosa. To our knowledge, this is the first reported case of such an association.