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

https://doi.org/10.1016/j.jaad.2014.12.020Get rights and content

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 patients with 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.

Section snippets

Methods

Diagnostic screening of postnatal peripheral blood specimens from 23,172 consecutive cases (13,945 male patients) submitted to the Mayo Clinic Cytogenetics Laboratory from March 4, 2008 to September 3, 2013 for CMA analysis using either a 4x44K or 4x180K oligonucleotide–based whole-genome cytogenomic microarray (Agilent Technologies, Santa Clara, CA) or Cytoscan HD array (Affymetrix, Santa Clara, CA) identified 22 cases of deletions that overlapped the STS gene (cases 1-22). Further information

Results

In all, 22 cases with an STS deletion were identified by CMA studies (Fig 1, A). For the 5 patients with accessible medical records, skin description, extracutaneous phenotypes, and gene content of the associated X chromosome deletion are described (Table I). Based on the American College of Medical Genetics guidelines for CMA testing,25 it is not surprising that the referral indications provided for almost all patients included developmental delay, autism, and/or dysmorphic features. Five of

Discussion

The potential impact to families of an XLI diagnosis is exemplified by literature describing at least 5 pregnancy terminations because of parental concern about the impact of the skin disease.1, 2 The present study suggests that dermatologists can expect to see patients with STS deletions identified unexpectedly through newer technologies. These cases incidentally found by CMA to have an STS deletion lacked the polygonal or “dirty” scales considered the hallmark of XLI; more common findings

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    Funding sources: None.

    Conflicts of interest: None declared.

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