Ring Chromosome 22 (Phelan-McDermid Syndrome)

A 3-year-old girl presents with global developmental delay, absent speech despite speech therapy, neonatal hypotonia, and characteristic facial features including dolichocephaly, long eyelashes, and bulbous nose. Chromosomal microarray confirms terminal deletion at 22q13.3 with SHANK3 loss. Karyotype analysis reveals the structure marked **B** in the diagram—a ring chromosome 22 formed by breakage and fusion of both chromosome arms. Which of the following best describes the pathophysiological consequence of the structural abnormality marked **B** in this patient?