arthrogryposis, distal, with impaired proprioception and touch

Arthrogryposis, distal, with impaired proprioception and touch is a condition primarily affecting the muscles and joints, with a significant impact on motor function and sensory perception. It is caused by pathogenic variants in the PIEZO2 gene, which plays an important role in regulating mechanosensation, including proprioception and touch. Affected individuals present in the neonatal period with features such as hypotonia and motor delay, and the disorder follows an autosomal recessive pattern in families. Precise prevalence estimates are not well established, and the clinical presentation may vary in severity.

Individuals with arthrogryposis, distal, with impaired proprioception and touch typically present with multiple neuromuscular and skeletal findings. Neonatal hypotonia, scoliosis, respiratory insufficiency, motor delay, dysarthria, and areflexia are consistently observed, marking the core clinical features of the condition. Many affected individuals also experience lower and upper limb muscle weakness, pes planus, and short stature, accompanied in some cases by camptodactyly, arachnodactyly, and a sandal gap. Global developmental delay is reported in a subset of patients, indicating that cognitive and developmental aspects can be involved. Additional less frequent features include feeding difficulties in infancy, gastroesophageal reflux, and a mild elevation of creatine kinase levels. Not all individuals experience all features, and severity varies considerably.

The condition is caused by variants in the PIEZO2 gene, which encodes a mechanosensitive ion channel that is fundamental for the perception of touch and proprioception. Disruption of this protein interferes with the normal signaling processes that guide motor control and joint movement. Arthrogryposis, distal, with impaired proprioception and touch follows an autosomal recessive inheritance pattern, meaning that an affected individual has received one altered copy of the gene from each parent. This pattern implies that each sibling of an affected individual has a 25% chance of inheriting the condition, underscoring the importance of genetic counseling for families.

Currently, management focuses on supportive care and symptom management, as there are no FDA-approved treatments specifically linked to this condition. Treatment is tailored to the individual and typically involves a multidisciplinary team, including physical therapy, occupational therapy, and respiratory support, to address motor difficulties, respiratory insufficiency, and speech challenges such as dysarthria. Regular surveillance is an essential part of long-term care, as ongoing monitoring helps to identify potential complications such as worsening scoliosis and respiratory issues before they become serious. It is important that families discuss treatment options with their healthcare team and consider genetic counseling to help understand the inheritance pattern and implications for family planning.

The clinical course of arthrogryposis, distal, with impaired proprioception and touch is highly variable, with the severity and range of symptoms differing considerably among affected individuals. With current standards of care, many individuals are able to manage their symptoms into adulthood despite challenges related to motor function and development. Outcomes described in medical literature continue to evolve as standards of care improve, and early intervention through a multidisciplinary approach can make a significant difference in quality of life. Families often find it helpful to connect with specialists familiar with the condition and to seek genetic counseling for guidance regarding long-term management and family planning.