Ichthyosis, Congenital, Autosomal Recessive 7

Description

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).

Clinical Features

Mizrachi-Koren et al. (2005) ascertained 2 consanguineous Israeli families of Arab Moslem origin with ichthyosis in 5 members, all of whom were born with normal-looking skin and developed fine whitish scales a few days after birth. The 3 patients in 'family 1' developed typical features of congenital recessive ichthyosis in childhood, including severe erythroderma associated with generalized fine scaling. The erythroderma lessened with age, but larger lamellar scales appeared and persisted through the years. Palmoplantar keratoderma manifested in all 3 patients with skin thickening and fissuring. Skin biopsy revealed epidermal compact hyperkeratosis, hypergranulosis, acanthosis, and papillomatosis. Over the years, these patients required repeated courses of antifungals and antibiotics for tinea pedis, onychomycosis, and recalcitrant malodorous secondary bacterial infections. In 'family 2,' the 2 affected individuals displayed only mild fine generalized scaling with minimal palmoplantar skin thickening, treated satisfactorily with skin moisturizers and emollients.

Mapping

Using homozygosity mapping in 2 consanguineous Israeli families with autosomal recessive congenital ichthyosis, Mizrachi-Koren et al. (2005) identified a 6.5-cM region on chromosome 12p11.2-q13 shared by all affected individuals. A maximum multipoint lod score of 4.79 was obtained at marker CH12SSR13, between markers D12S345 and D12S390. The authors stated that this locus was 5 cM centromeric to the locus at 12q13 previously described by Hatsell et al. (2003) for a form of exfoliative ichthyosis (see 607936).

See ARCI13 (617574) for a congenital ichthyosis locus that maps close to the locus for ARCI7.

Molecular Genetics

Exclusion Studies

In 2 consanguineous Israeli families with ARCI, Mizrachi-Koren et al. (2005) analyzed the PPHLN1 gene (608150), a candidate gene encoding a protein involved in the cornification process, but no mutations were identified within the coding region.