Diagnosing Coexisting Conditions of Angelman and Klinefelter Syndromes Using Chromosomal Microarray

We report here a 4-year-old male patient who presented with clinical features of Angelman syndrome (AS, OMIM 105830) including dysmorphic features, hypotonia, lack of language development, ataxia, severe developmental delay, and seizures. Due to insurance denial for DNA methylation test, a chromosomal microarray (CMA) was performed, which showed an approximately 5.0 Mb deletion of Prader-Willi/AS critical region (15q11.2 to q13.1). Subsequent Prader-Willi/AS methylation analysis was consistent with the diagnosis of AS. Gain of an X chromosome (Klinefelter syndrome, KS) was also detected by CMA. KS is not usually diagnosed before puberty due to lack of specific clinical features in early childhood. It is unclear if there is any direct association between these two genetic disorders. There has only been one other published case, to our knowledge, of a patient with coexistence of AS due to 15q11.2-q13 deletion and KS. CMA is a fast and effective diagnostic test to determine multiple genetic disorders. Early genetic diagnostic testing using CMA as an alternative first-step diagnostic genetic testing for children with clinical suspicion of AS would be beneficial.