Ichthyosis With Confetti
DISEASE CARD
| Disease group | Keratinization disorders |
|---|---|
| DISEASE NAME | ICHTHYOSIS WITH CONFETTI |
| Synonymous | Congenital reticular erythroderma, Congenital Erythrokeratoderma, Ichthyosis Variegata |
| Estimated prevalence | 1 / 1 000 000 |
| OMIM | 609165 |
| Inheritance | Autosomal dominant |
| Gene (s) | KRT10 (148080) |
Definition
Ichthyosis with confetti (IWC) is a rare skin (keratinization) disorder caused by mutations in the KRT10 gene (17q21.2). (see Ichthyosis classification)
Clinical Description
IWC patients are born with severe ichthyosiform erythroderma that remains throughout the first years of life. Defective skin barrier and poor skin integrity may lead to bacterial infections, growth failure and early death. The skin appearance changes with age. Within the first months of life, palmoplantar keratoderma usually becomes apparent. Ichthyotic, non-scaling patches appear in a reticulated pattern in (late) infancy or early childhood. During the age of 3-10 years, white islands appear in a random distribution on the whole integument. With time, these confetti-like spots increase in number and size (up to 2 cm). The white spots are considered to be localized areas of spontaneous healing, due to recombination events (mosaic). Phenotypical expression varies within patients, as some develop hundreds to thousands of spots whereas others only a few. Rarely, patients complain about pruritus. Squamous cell carcinomas have been reported. 1-3
Pathogenesis
Keratin 10 levels are reduced in diseased skin. Ultrastructurally, a reduction of cytokeratin filaments can be seen with poor contact to desmosomes. IWC is caused by heterozygous frameshift mutations in the C-terminal tail domain of KRT10 gene. These mutations result in an alternative reading frame that produces an arginine-rich C-terminal peptide, redirecting keratin 10 from the cytokeratin network to the nucleolus. The full consequences of nucleolar localization of KRT10 are unknown, but a high arginine content suggests a possible interference with RNA molecules. Ribosome biogenesis, protein synthesis, cell cycle, DNA repair and replication might also be affected.2, 4 Recently, a de novo mutation in KRT1 has also been reported as disease causing.5
Diagnosis
A skin biopsy in neonates/infants is recommended as early diagnosis is difficult. Histopathological findings include band-like parakeratosis, psoriasiform acanthosis, absence of the granular layer, vacuolization of the keratinocytes with binuclear cells in the upper epidermis and occasionally deposition of amyloid in the dermis.6 Typical ultrastructural findings are reduced intermediate filaments in the suprabasal layers of the epidermis, as well as perinuclear shells of keratin filaments and paucity of lamellar bilayers in the stratum corneum. Mislocalization of mutant KRT10 to the nucleolus can be determined by co-staining with fibrillarin.
Genetic testing by DNA sequencing of the KRT10 (and KRT1) gene is expedient for genetic counselling and prenatal diagnosis.2
Differentialdiagnosis
Epidermolytic ichthyosis (in neonates); severe atopic dermatitis with pityriasis alba or postinflammatory pigmentary alterations
Treatment
Treatment is limited to symptomatic measures (see epidermolytic ichthyosis). Standard treatment involves the use of emollients. There are reports about effectiveness of oral retinoids.3