Expanding the phenotypic spectrum of hunter–McAlpine syndrome: a new case of distal 5q duplication and review of the literature

Distal 5q duplications are associated with Hunter–McAlpine syndrome, a chromosomal disorder characterized by growth retardation, microcephaly, developmental delay, intellectual disability, and dysmorphic features. The clinical spectrum remains incompletely defined because of the variability in the size and gene content of the reported duplications, as well as the frequent presence of additional chromosomal imbalances. We report a distal 5 q duplication (5q34–> qter) concomitant with a terminal Yq deletion (Yq11.223–> qter) and provide a review of the literature. We describe an 11-year-old boy with growth retardation, microcephaly, developmental delay, moderate intellectual disability, severe speech impairment, behavioral abnormalities, dysmorphic features, dental anomalies, and bilateral fifth-finger clinodactyly. Karyotyping showed additional material on the long arm of chromosome Y. Array comparative genomic hybridization identified an approximately 20 Mb duplication of 5q34–> qter and an approximately 34 Mb terminal deletion of Yq11.223–> qter. Fluorescent in situ hybridization confirmed translocation of distal chromosome 5 material onto the Y chromosome and the loss of the terminal Yq region. Parental analyses were normal, indicating a de novo rearrangement. The deleted Yq region encompassed the AZFc interval, including the DAZ gene cluster, as well as part of the distal AZFb region. The present case represents a distal 5q duplication due to a derivative Y chromosome resulting from a de novo t(Y;5) translocation, and, to our knowledge, the first reported case of Hunter–McAlpine syndrome associated with loss of the DAZ gene cluster. Combined with a structured review of the literature, this study expands the phenotypic and cytogenetic spectrum of Hunter–McAlpine syndrome.