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).
Wu and Lee (2011) ascertained 6 patients, 5 male and 1 female, with autosomal recessive congenital ichthyosis in an aboriginal village in the central mountains of Taiwan. All patients had collodion membrane at birth, followed by the progressive ... Wu and Lee (2011) ascertained 6 patients, 5 male and 1 female, with autosomal recessive congenital ichthyosis in an aboriginal village in the central mountains of Taiwan. All patients had collodion membrane at birth, followed by the progressive appearance of generalized fine erythrodermic scales. Mild alopecia and palmoplantar hyperlinearity were also present. Microscopic examination revealed thick orthohyperkeratosis, hypergranulosis, moderate acanthosis, and mild perivascular lymphocytic infiltrates. Radner et al. (2013) studied a 30-year-old Tunisian woman who had collodion membrane at birth and subsequently developed ichthyosiform erythroderma, with pronounced facial erythema and fine whitish scales present over her entire body, except for her legs, where the scales were large and brownish. She had moderate hyperlinearity of the palms, with yellowish plantar keratoderma on the pressure zones. Multiple melanocytic nevi were present on the backs of her hands. Histologic analysis of a patient skin biopsy showed acanthosis with thickening of the stratum granulosum, psoriasiform epidermal hyperplasia, and normal size of the detached stratum corneum. Ophthalmologic and echocardiographic examinations were normal. Eckl et al. (2013) studied a large, multiply consanguineous German family segregating autosomal recessive congenital ichthyosis, in which the female proband presented at birth with extreme ectropion and eclabium with collodion membranes, which resolved within 1 week. After that, she showed moderate lamellar ichthyosis with mild erythroderma and improvement in the summer months. In addition, there was hypohidrosis, although sweating occurred on her nose. At 3 years of age, she showed severe scaling of the scalp and a pronounced keratotic lichenification with a prematurely aged appearance. She suffered from repeated uncomplicated bacterial and pityrosporum infections of the skin on her back and from pruritus. At 7 years of age, the scaling was lighter in color and milder, and she exhibited exacerbated erythroderma; strong lichenification was still present. Light microscopy revealed moderate compact orthohyperkeratosis, with hyperplastic papillomatous epidermis, and mild acanthosis. Ultrastructural analysis of skin biopsy specimens from the proband and an affected relative showed mild acanthosis and moderate to strong orthohyperkeratosis, with cleft-like inclusions in the stratum corneum and irregular vesicular structures in the granular layer.
In 6 Taiwanese patients with ARCI associated with SNPs on chromosome 15q26, Wu and Lee (2011) found that the genotype at the most strongly associated SNP (dbSNP rs6598375) was GG for all patients and was AA for all ... In 6 Taiwanese patients with ARCI associated with SNPs on chromosome 15q26, Wu and Lee (2011) found that the genotype at the most strongly associated SNP (dbSNP rs6598375) was GG for all patients and was AA for all 11 controls. Analysis of an additional 53 unaffected individuals from the isolated mountain village showed a prevalence of 3.12% for the dbSNP rs6598375 G allele compared to 100% among patients (p = 1.26 x 10(-20)), and the estimated prevalence of ARCI in the village (9.76 x 10(-4)) was close the number of patients identified. Sequencing the exons and exon-intron boundaries of 6 genes within the 0.9-Mb region of homozygosity shared by the 6 patients revealed no mutations. Radner et al. (2013) studied 4 patients from 3 consanguineous Tunisian families with features of Weill-Marchesani-like syndrome (613195), including short stature, brachydactyly with joint stiffness, microspherophakia, ectopia lentis, and mitral valve defects, who also exhibited collodion membrane at birth that evolved to generalized ichthyosis. The patients all shared a 100-kb deletion on chromosome 15q36.3 between SNPs dbSNP rs1080492 and dbSNP rs7179355 that encompassed the first 3 exons of the ADAMTS17 gene (607511), the complete sequence of the noncoding RNA FLJ42289, and exon 13 of the CERS3 gene, including the 3-prime UTR. Sequencing of the CERS3 gene in an unrelated Tunisian woman with isolated ichthyosis revealed a homozygous splice site mutation in the CERS3 gene (615276.0001), suggesting that the previously unreported skin phenotype in the patients with Weill-Marchesani-like syndrome was due to partial deletion of the CERS3 gene. The splice site mutation was not found in 96 population-matched controls, and analysis of the patient's skin compared to that of healthy controls suggested that mutated CERS3 affects the terminal differentiation process in human skin. In a large, multiply consanguineous German family segregating autosomal recessive congenital ichthyosis mapping to chromosome 15q, Eckl et al. (2013) performed whole-exome sequencing and identified a homozygous missense mutation in the CERS3 gene (W15R; 615276.0002) that segregated fully with disease in the family and was not found in 200 control chromosomes. Analysis of CERS3 in 80 additional ARCI probands who were negative for mutation in known ARCI-associated genes revealed no further mutations.