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

## TL;DR

A nine-year-old boy with a PIEZO2 duplication shows a range of neurological and musculoskeletal issues, expanding the known effects of this gene.

## Contribution

This case expands the mutational spectrum of recessive PIEZO2-related diseases with a novel intragenic duplication.

## Key findings

- The patient exhibited global motor delay, sensory neuropathy, and musculoskeletal abnormalities due to a PIEZO2 duplication.
- The duplication disrupted PIEZO2 protein function, leading to impaired mechanotransduction and proprioceptive deficits.
- The case highlights the need for further research to refine genotype-phenotype correlations in PIEZO2-related disorders.

## Abstract

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.