The phenotype spectrum of X-linked ichthyosis identified by chromosomal microarray

Background: Steroid sulfatase (STS) gene disruption causes X-linked ichthyosis (XLI). Interrogating the entire genome through chromosomal microarray (CMA), a test primarily used to screen patients with noncutaneous congenital anomalies, may detect STS deletions incidentally. Objective: We sought to determine the variability of skin features associated with STS deletions diagnosed through CMA and to compare these findings with XLI cases reported in the literature and recognized in a dermatology clinic. Methods: Male patientswith an STS deletion were identified from 23,172 consecutive postnatal blood samples tested with CMA at Mayo Clinic. A comparison group of male patients with biochemically confirmed XLI was ascertained in the dermatology clinic. The available patient medical records, skin histopathology, and photographs were evaluated and a literature search of patients with XLI was conducted. Results: Children whose diagnosis was made incidentally through CMA had milder skin phenotypes, including dryness or eczema, or both, and did not manifest the polygonal or "dirty'' scale described as typical of XLI in the literature. Limitations: The small sample size, limited clinical information, and assessment by nondermatologists in a subset of cases may have influenced the results. Conclusion: STS deletions may cause a milder skin phenotype than the typical presentation of XLI.