Genetic Diagnostic Elucidation of a Patient With Multiorgan Granulomas, Facial Peculiarities, and Psychomotor Retardation.

We report the case of a 19-years-old patient who presented with a perplexing variety of symptoms which included remarkable facial features, intellectual disability, granulomatous upper lip swelling (previously diagnosed as Melkersson-Rosenthal syndrome), Crohn's-like disease, non-productive cough, and a granulomatous mass localized in the left lung. Chronic granulomatous disease (CGD) was diagnosed using dihydrorhodamine 123 assay that showed low levels of phagocytic NADPH-oxidase. DNA sequencing revealed a heterozygous mutation in the gene on chromosome 7. As remarkable facial features and psychomotor retardation are not associated with CGD, a more detailed genetic work-up using fluorescence hybridization was performed. A microdeletion in 7q11.23 on one allele indicated Williams-Beuren syndrome (WBS). The gene and its two pseudogenes are part of a highly repetitive region within 7q11.23 and are prone to recombination events and deletions. Such deletions can involve both the WBS critical region and the wildtype gene, as was the case for our patient. The second allele of the gene was affected by the frequent c.75.76delGT mutation that stems from a recombination of the wildtype gene with one of its pseudogenes. In conclusion, patients with -deficient CGD may also harbor microdeletions that result in WBS or other hereditary disorders; therefore, it is important to perform a thorough genetic analysis in order to initiate appropriate therapy for these patients.