Isodicentric 15q (idic(15)/Dup15q Syndrome)

A 4-year-old boy with developmental delay and autism spectrum disorder is referred for genetic evaluation. His karyotype analysis reveals the abnormality marked as **B** in the diagram—a supernumerary marker chromosome with two centromeres and duplicated proximal 15q segments. His mother reports neonatal hypotonia, severely delayed speech (5–10 words at age 4), prominent hand-flapping stereotypies, poor eye contact, and medically refractory seizures beginning at age 3 with polyspike-and-wave discharges on EEG. Chromosomal microarray confirms 4 copies of the 15q11.2–q13.1 region including the imprinted UBE3A gene. Which of the following best explains why this patient's phenotype is clinically manifest despite the supernumerary chromosome **B** being present in only one copy?