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

Acta Derm Venereol. 2016 Nov 2;96(7):932-937. doi: 10.2340/00015555-2418.

Abstract

Autosomal recessive congenital ichthyosis (ARCI) represents a heterogeneous group of rare disorders of cornification with 3 major subtypes: harlequin ichthyosis (HI), lamellar ichthyosis (LI) and congenital ichthyosiform erythroderma (CIE). A 4th subtype has also been proposed: pleomorphic ichthyosis (PI), characterized by marked skin changes at birth and subsequently mild symptoms. In nationwide screenings of suspected cases of ARCI in Denmark and Sweden, we identified 132 patients (age range 0.1-86 years) classified as HI (n = 7), LI (n = 70), CIE (n = 17) and PI (n = 38). At birth, a collodion membrane or similar severe hyperkeratosis was reported in almost all patients with HI and LI, and in nearly half of patients with CIE and PI. Persistent ectropion was more common in HI (85%) and LI (57%), than in CIE (35%) and PI (5%). Anhidrosis was a frequent problem in all 4 groups (58-100%). A scoring (0-4) of ichthyosis/ery-thema past infancy showed widely different mean values in the subgroups: HI (3.2/3.1), LI (2.4/0.6), CIE (1.8/1.6), PI (1.1/0.3). Novel or recurrent mutations were found in 113 patients: TGM1 (n = 56), NIPAL4 (n = 15), ALOX12B (n = 15), ABCA12 (n = 8), ALOXE3 (n = 9), SLC27A4 (n = 5), CYP4F22 (n = 3), PNPLA1 (n = 1) and ABHD5 (n = 1). In conclusion, by performing a deep phenotyping and gene screening, ARCI can be definitely diagnosed in 85% of cases in Scandinavia, with a prevalence of 1:100,000 and > 8 different aetiologies.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Child
  • Child, Preschool
  • Consanguinity
  • DNA Mutational Analysis
  • Denmark / epidemiology
  • Female
  • Genes, Recessive
  • Genetic Predisposition to Disease
  • Genetic Testing
  • Genotype
  • Humans
  • Ichthyosiform Erythroderma, Congenital / classification
  • Ichthyosiform Erythroderma, Congenital / epidemiology*
  • Ichthyosiform Erythroderma, Congenital / genetics*
  • Infant
  • Male
  • Middle Aged
  • Mutation / genetics*
  • Sweden / epidemiology