Attenuated Phenotype in a Patient with Prader-Willi Syndrome and Duplication 16P11.2 Detected by Chromosomal Microarray

ABSTRACT Objective: We report an unusual case of Prader-Willi Syndrome (PWS) presenting with clinical signs and symptoms suggestive of Angelman Syndrome (AS), without exclusive features of PWS. Methods: A deletion in the 15q11-13 region is associated with 2 distinctive genetic syndromes depending on the parent of origin: AS and PWS. AS is characterized by developmental delays, seizures, microcephaly, movement or balance disorders, speech disorders, and happy demeanor. PWS is characterized by hypotonia, hyperphagia, and developmental delays. An 11.5-year-old female was evaluated for developmental delay with cognitive disabilities, minimal speech, echolalia, and continuous hand motions. The patient had a pleasant but minimally interactive demeanor. Results: Chromosomal microarray analysis revealed a 5.02 Mb interstitial deletion of 15q11.2>q13.1 (base pairs 21,192,943 to 26,213,571), consistent with PWS or AS, and a 604 kb interstitial duplication of 16p11.2 (base pairs 29,530,197 to 30,134,432). Based on her presentation, AS was suspected; however, methylation analysis confirmed the diagnosis of PWS, with the presence of only the maternal copy of 15q11.2q13.1. Conclusion: Although variable phenotypic presentation of PWS has been reported, this case is particularly unusual in having only a few typical features of PWS while presenting as possible AS. We postulate that the 16p11.2 duplications, involving an autism susceptibility region, may have attenuated some features of PWS. Abbreviations: AS = Angelman Syndrome; ASD = Autism Spectrum Disorder; BMI = body mass index; CMA = chromosomal microarray; PWS = Prader-Willi Syndrome