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Regional difference in expression of characteristic abnormality of harlequin ichthyosis in affected fetuses
M Akiyama1, B A Dale, L T Smith
1Department of Biological Structure, Medicine/Dermatology, University of Washington School of Medicine, Seattle, USA. akiyama@mc.med.keio.ac.jp
Insights
Harlequin ichthyosis (HI) is a severe skin disorder. Prenatal diagnosis is possible in the second trimester by examining fetal skin biopsies for characteristic morphological abnormalities.
Area of Science:
- Dermatology
- Fetal Medicine
- Genetics
Background:
- Harlequin ichthyosis (HI) is a severe congenital ichthyosis characterized by a thick stratum corneum in newborns.
- Early identification of HI is crucial for management and counseling.
Purpose of the Study:
- To investigate the prenatal morphological and molecular characteristics of Harlequin ichthyosis.
- To determine the feasibility of prenatal diagnosis of HI through fetal skin biopsies.
Main Methods:
- Examination of skin specimens from multiple body regions of three HI-affected fetuses diagnosed prenatally.
- Morphological analysis of skin abnormalities, including lamellar granules and intercellular lamellae.
- Immunoblot analysis of epidermal extracts to study profilaggrin and filaggrin expression.
Main Results:
- Characteristic HI morphological abnormalities were observed in all examined fetal skin regions by the late second trimester.
- Abnormalities were more pronounced in hair canal cornified cells compared to interfollicular epidermis.
- Profilaggrin was prominent in hairy skin, while filaggrin was prominent in the palm, suggesting altered protein metabolism in HI.
Conclusions:
- Prenatal diagnosis or exclusion of Harlequin ichthyosis is feasible from skin biopsies taken in the late second trimester.
- HI phenotype expression in hairy skin is linked to keratinization and abnormal filaggrin metabolism.
- The study supports the utility of fetal skin biopsy for prenatal diagnosis of HI.
Abstract:
Harlequin ichthyosis (HI) is a severe congenital ichthyosis in which newborn infants are covered with a thick plate of stratum corneum. We examined skin specimens from a variety of regions of the body including the scalp, face, tongue, trunk, upper and lower extremities, digits, palms, and soles of three fetuses affected with HI that were diagnosed prenatally. In all the skin regions, characteristic morphological abnormalities (absent or abnormal lamellar granules and intercellular lamellae, lipid inclusions in the cornified cells) were expressed in the late second trimester of the fetal period. The cornified cells in hair canals showed morphological abnormalities of HI more strongly than the interfollicular epidermis. Immunoblot study of epidermal extracts revealed that profilaggrin was much more prominent than filaggrin in all the hairy skin regions where the hair canals were extensively keratinized, but filaggrin was prominent in the palm. These observations support the idea that, in the hairy skin, HI phenotype expression is associated with keratinization and abnormal filaggrin metabolism in hair. In addition, the prenatal diagnosis or prenatal exclusion of HI is thought to be possible from whichever site of the fetal body the skin biopsy is taken in the late second trimester of the fetal period.