Neuromuscul Disord 2019 Jan 8;29(1):75-79. Epub 2018 Nov 8.
Centre de Référence de Pathologie Neuromusculaire Nord/Est/Ile de France, Institut de Myologie, CHU La Pitié-Salpêtrière, APHP, Paris, France.
PIEZO2 mutations have been described in dominant arthrogryposis, but homozygous mutations of PIEZO2 may also be responsible for more complex clinical patterns, associating distal arthrogryposis, neonatal respiratory insufficiency, scoliosis and proprioceptive impairment. We report here two sisters presenting with these clinical and genetic features. They had a similar phenotype, with severe hypotonia and respiratory distress at birth, delayed acquisition of motor milestones and need of scoliosis surgery. Hypotonia and alteration of proprioception were at the forefront of clinical examination for both, along with areflexia, hyperlaxity, cutis laxa, and discrete facial dysmorphy. Electrophysiological studies, including electroneuromyography and sensory evoked potentials, showed a mild sensory axonopathy without any myopathic features, but revealed a peripheral proximal lemniscal defect. Creatine kinase, muscular MRI and biopsy were normal, as well as cerebral MRI and neurometabolic biological explorations. They had a moderate restrictive syndrome on respiratory function tests and cardiac function was normal. Molecular studies performed on a panel of genes involved in distal arthrogryposis disclosed a nonsense homozygous c.3241C > T (p.Arg1051*) mutation in the PIEZO2 gene, which was also present at the heterozygous state in their mother's DNA. This new PIEZO2 mutation was in accordance with the phenotype combining arthrogryposis, scoliosis, hyperlaxity and proprioceptive impairment.