Whole genome sequencing reveals diagnosis in a 12-month-old child with elevated creatinine kinase, pseudohypertriglyceridemia, and a complex phenotype.

INTRODUCTION: Contiguous gene deletion syndromes (CGDSs) can be inherited or the result of microdeletions (eg, resulting from crossing-over errors) in gene-rich chromosome regions. Molecular mechanisms leading to chromosome loss in hotspot areas, such as errors in chromosome crossing-over events, can explain phenotypic presentations in CGDSs. Accurate interpretation of laboratory results in the context of clinical presentation can guide genetic testing that supports a timely diagnosis so that quicker interventions can improve clinical outcomes. Treatment of genetic disorders not only requires timely and accurate treatment, however, but also necessitates management and education of family members who care for the patient. Xp21.3-p21.2 deletion syndrome is a CGDS that has been documented in more than 100 male patients; it presents with primary adrenal insufficiency in the neonatal period.

METHODS: Here, we report the largest Xp21.3-p21.2 CGDS series to date.

RESULTS AND DISCUSSION: Initial presentation was incorrectly diagnosed as adrenal insufficiency only, despite excessively elevated creatinine kinase and triglycerides, which could have expedited the correct diagnosis of Xp21.3p21.1 CGDS by guiding whole genome or targeted sequencing.