Autosomal recessive congenital ichthyosis (ARCI) is a heterogeneous group of disorders of keratinization characterized primarily by abnormal skin scaling over the whole body. These disorders are limited to skin, with approximately two-thirds of patients presenting severe symptoms. The ... Autosomal recessive congenital ichthyosis (ARCI) is a heterogeneous group of disorders of keratinization characterized primarily by abnormal skin scaling over the whole body. These disorders are limited to skin, with approximately two-thirds of patients presenting severe symptoms. The main skin phenotypes are lamellar ichthyosis (LI) and nonbullous congenital ichthyosiform erythroderma (NCIE), although phenotypic overlap within the same patient or among patients from the same family can occur (summary by Fischer, 2009). Neither histopathologic findings nor ultrastructural features clearly distinguish between NCIE and LI. In addition, mutations in several genes have been shown to cause both lamellar and nonbullous ichthyosiform erythrodermal phenotypes (Akiyama et al., 2003). At the First Ichthyosis Consensus Conference in Soreze in 2009, the term 'autosomal recessive congenital ichthyosis' (ARCI) was designated to encompass LI, NCIE, and harlequin ichthyosis (ARCI4B; 242500) (Oji et al., 2010). NCIE is characterized by prominent erythroderma and fine white, superficial, semiadherent scales. Most patients present with collodion membrane at birth and have palmoplantar keratoderma, often with painful fissures, digital contractures, and loss of pulp volume. In half of the cases, a nail dystrophy including ridging, subungual hyperkeratosis, or hypoplasia has been described. Ectropion, eclabium, scalp involvement, and loss of eyebrows and lashes seem to be more frequent in NCIE than in lamellar ichthyosis (summary by Fischer et al., 2000). In LI, the scales are large, adherent, dark, and pigmented with no skin erythema. Overlapping phenotypes may depend on the age of the patient and the region of the body. The terminal differentiation of the epidermis is perturbed in both forms, leading to a reduced barrier function and defects of lipid composition in the stratum corneum (summary by Lefevre et al., 2006). In later life, the skin in ARCI may have scales that cover the entire body surface, including the flexural folds, and the scales are highly variable in size and color. Erythema may be very mild and almost invisible. Some affected persons exhibit scarring alopecia, and many have secondary anhidrosis (summary by Eckl et al., 2005). For a general phenotypic description and discussion of genetic heterogeneity of autosomal recessive congenital ichthyosis, see ARCI1 (242300).
Grall et al. (2012) studied 6 affected individuals from 2 families segregating autosomal recessive congenital ichthyosis (ARCI). All were born as collodion babies and later developed generalized ichthyosis, with mild to moderate fine grayish-white scales and moderate erythroderma ... Grall et al. (2012) studied 6 affected individuals from 2 families segregating autosomal recessive congenital ichthyosis (ARCI). All were born as collodion babies and later developed generalized ichthyosis, with mild to moderate fine grayish-white scales and moderate erythroderma and palmoplantar keratoderma. Histopathology of affected skin presented a thicker cornified layer, pronounced desquamation of upper loosely packed scales, and hypergranulosis with increased amounts of keratohyalin. Conspicuous regularly spaced small holes were visible in the granular layer. Electron microscopy showed more than 40 layers of cornified lamellae, consisting partly of loose content but otherwise mostly homogeneous, with some lipid droplets, membrane structures, and increased amounts of melanosomal remnants but only a few remnants of cholesterol crystals. In the transition to the living epidermal layers, there were many transit cells and numerous vesicular structures within the cells of the granular layer, corresponding to the holes observed by light microscopy.
From a cohort of 46 consanguineous ARCI families that had undergone genomewide linkage analysis and in which no causative mutation had been found in genes known to have a role in ARCI, Grall et al. (2012) selected 10 ... From a cohort of 46 consanguineous ARCI families that had undergone genomewide linkage analysis and in which no causative mutation had been found in genes known to have a role in ARCI, Grall et al. (2012) selected 10 families in which affected individuals showed a homozygous haplotype in the 6p21 region containing the candidate gene PNPLA1 (612121). Sequencing identified 2 distinct PNPLA1 mutations in 2 of the families: 3 affected sibs from an Algerian family were homozygous for a nonsense mutation (E131X; 612121.0001), and 3 affected children from a Moroccan family were homozygous for a missense mutation (A59V; 612121.0002). The mutations segregated with disease in each family and were not found in a panel of 384 control DNA samples.