Expanding the Clinical Spectrum of PIEZO2 Duplications: A Case of Global Motor Delay, Congenital Sensory Neuropathy, and Musculoskeletal Abnormalities.

PIEZO2 encodes a mechanosensitive ion channel essential for touch perception, proprioception, and interoception, with biallelic loss-of-function variants known to cause a recessive mechanosensory neuropathy characterized by hypotonia and skeletal abnormalities; however, intragenic duplications have rarely been reported. We present a nine-year-old male with global motor delay, congenital hypotonia, distal muscle weakness, sensory neuropathy, thoracolumbar neuromuscular scoliosis, and multiple orthopedic abnormalities, along with microcephaly, cryptorchidism, chronic urinary incontinence, and early failure to thrive. Chromosomal microarray revealed a duplication at chromosome 18p11.22 involving PIEZO2, and exome-based copy number variant analysis confirmed a homozygous intragenic duplication. The duplicated exons are predicted to disrupt protein structure and function, resulting in impaired mechanotransduction, which is consistent with the patient's proprioceptive deficits and musculoskeletal phenotype. This case likely expands to the mutational spectrum of recessive PIEZO2-related diseases. Care is supportive and multidisciplinary. Further case aggregation is needed to refine genotype-phenotype correlations.