Autosomal Recessive Congenital Ichthyosis in Sweden and Estonia: Clinical, Genetic and Ultrastructural Findings in Eighty-three Patients

Abstract

Congenital (non-bullous) ichthyosis is a rare group of keratinizing disorders which can be tentatively subclassified based on clinical criteria, analysis of transglutaminase 1 gene mutations and electron microscopy of epidermis. We studied 83 patients who were all on topical therapy and in 16 cases also on oral retinoids. Three main groups of patients were distinguished: (A) those with transglutaminase 1 gene mutations (n=44), (B) those without transglutaminase 1 gene mutations showing a coarse, generalized scaling (n=19), and (C) those without transglutaminase 1 gene mutations showing only fine or focal scaling (n=20). On clinical scoring, patients in group A were more hyperkeratotic and less erythematous than those in group B (p < 0.05). Anhidrosis was recorded in nearly all patients (> or = 80%), but ectropion and a collodion phenotype at birth were more common in group A versus other groups. Ultrastructurally, a high frequency of type I (Anton-Lamprecht's classification) was found in all three groups (37-63%), 20 cases of type II in group A and a few cases of types III and IV in groups B and C, respectively. In conclusion, transglutaminase 1 gene mutation is a major cause of congenital ichthyosis in Sweden and Estonia, and is often associated with severe scaling and ultrastructural type II in corneocytes. The transglutaminase-unrelated cases are more heterogeneous, probably reflecting a more varied aetiology.

Spectrum of Autosomal Recessive Congenital Ichthyosis in Scandinavia: Clinical Characteristics and Novel and Recurrent Mutations in 132 Patients

“…Consanguinity in the last 3 generations was traced in 6 families. Many of the Swedish ARCI patients have been reported previously with respect to clinical and ultrastructural findings in the skin, and whether TGM1 mutations were present, although without providing any mutation details (22). One Swedish family with mother and 2 daughters affected with LI was previously reported to have novel compound TGM1 mutations, whereas the father was a heterozygote carrier (28).…”

“…Sjögren-Larsson syndrome) were not included; neither were families with a typical dominant mode of inheritance over several generations. After initial clinical screening, 138 patients underwent more extensive examinations, at which at least 2 of the authors (AG, AB, FB, MV, AV) participated and agreed on the diagnosis, the subtype of ARCI (HI, LI, CIE or PI) according to previously established criteria (1,18), and a scoring of ichthyosis and erythema severity using a standardized protocol (22), whereby all parts of the body (trunk, arms, legs, face, scalp, hands, feet, elbows/knees and flexural areas) are first visually scored from 0 to 4 (none to very severe), followed by multiplying the score values of each area with its fractional contribution to the body surface using "the rule of 9" (from 0.01 for hands to 0.36 for trunk); the sum of these products represents the patient's whole body score with a maximal value of 4.…”

“…Our study was initiated over a decade ago with the explicit aim of examining as many clinically suspicious cases of ARCI as possible in 2 neighbouring Scandinavian countries, Sweden and Denmark, with a combined population of 15 million. In an attempt to provide a full overview of the genotypic and phenotypic spectra of ARCI in Scandinavia, this paper now presents a compilation of our new data, together with some previously published results on the same cohort of patients (20,22,25,(28)(29)(30)(31)(32)(33)(34).…”

“…The suggested umbrella term PI encompasses several distinct conditions: self-improving collodion ichthyosis (SICI) (19), ichthyosis prematurity syndrome (IPS) (20), bathing-suit ichthyosis (BSI) (21), and congenital ichthyosis with fine/mild scaling (CIFS) (22). Many of these conditions have a known aetiology; for example: TGM1, ALOX12B and ALOXE3 mutations in SICI and BSI (23,24), and SLC27A4 (9q34.11) mutations in IPS (25).…”

Thematic review series: Skin Lipids. Pathogenesis of permeability barrier abnormalities in the ichthyoses: inherited disorders of lipid metabolism

“…However, in CIE, several variable ultrastructural features were observed only in subsets of patients. These variable findings include the following: 1) an absence of electron-lucent lamellae; 2) abnormal spacing and interruptions of lamellar structures; and 3) intracellular lipid droplets and vesicular complexes, within both the SC and the SG (10,46,56,66,67). An alternative classification of the variable ultrastructural findings in ARCI is widely applied in Europe: type I is characterized by abundant lipid droplets within corneocytes; type II shows polygonal clefts within the SC; type III shows vesicular and membranous structures in the SG; and type IV is characterized by lentiform swollen areas within corneocytes and perinuclear accumulation of curved membranes in the SG (55,66).…”