congenital muscular dystrophy due to integrin alpha-7 deficiency

Congenital muscular dystrophy due to integrin alpha-7 deficiency is a rare inherited disorder affecting the muscles, marked by early motor delays and progressive muscle weakness. The condition is caused by alterations in the ITGA7 gene, which encodes the integrin alpha-7 protein important for the extracellular matrix and muscle integrity. Affected individuals typically present in infancy with motor challenges and, in some cases, later develop additional complications such as spinal curvature and respiratory difficulties. It affects fewer than 1 in a million people, underscoring its very rare occurrence.

The clinical presentation centers on a constellation of muscle-related difficulties. Nearly all affected individuals exhibit motor delay, increased variability in muscle fiber diameter, and muscle weakness, which are considered characteristic features of the condition. Many children also show signs such as Gowers sign and hypotonia, while some experience torticollis and elevated circulating creatine kinase concentrations. In a subset of affected individuals, cognitive challenges manifest as intellectual disability, adding a layer of complexity to the neuromuscular symptoms. Not all individuals experience all features, and severity varies considerably.

The condition is caused by pathogenic variants in the ITGA7 gene, which disrupts the production of integrin alpha-7, a protein that plays a critical role in connecting muscle cells to the extracellular matrix. This disruption leads to compromised muscle integrity and function. It is inherited in an autosomal recessive pattern, meaning that an affected individual inherits a defective copy of the gene from each parent. This pattern also implies that the condition is more commonly observed in families where parents share a common ancestor, thereby increasing the likelihood that both are carriers. Genetic counseling is recommended for families to better understand inheritance risks and implications for family planning.

Currently, management focuses on supportive care and symptom relief, as no specific foundational therapies or approved treatments are available. Treatment is tailored to the individual and typically involves interventions such as physical and occupational therapy, respiratory support, and regular monitoring by a multidisciplinary team. Genetic counseling is advised to help families understand the condition and explore management options. Patients should discuss treatment options with their healthcare team to determine which supportive strategies best address their individual needs.

The overall course of congenital muscular dystrophy due to integrin alpha-7 deficiency is variable, with outcomes influenced by the severity of muscle weakness, the presence of cognitive or intellectual challenges, and access to specialized care. Many affected individuals experience an initial period of motor delay and, in some cases, a subsequent loss of previously acquired abilities, followed by stabilization or gradual progression of symptoms such as proximal muscle weakness and respiratory insufficiency. Outcomes described in medical literature continue to evolve as standards of care improve. Families often find it helpful to connect with specialists and genetic counselors who can offer guidance and support as care strategies are refined over time.

There is an active clinical trial exploring new treatment approaches for this condition. Clinical trials are underway investigating novel strategies, and individuals interested in clinical trials can search ClinicalTrials.gov or consult their care team about eligibility.