Distal spinal muscular atrophy type 1

IGHMBP2

Distal Spinal Muscular Atrophy Type 1 (DSMA1), also known as Distal Hereditary Motor Neuropathy Type V or Spinal Muscular Atrophy with Respiratory Distress Type 1 (SMARD1), is a rare neuromuscular disease characterized by muscle weakness and atrophy predominantly affecting the distal muscles, those farthest from the center of the body, such as the hands and feet. It is a genetic disorder caused by mutations in the IGHMBP2 gene, which is located on chromosome 11q13.3. This condition is inherited in an autosomal recessive manner, meaning that an individual must inherit two copies of the mutated gene, one from each parent, to be affected.

Symptoms and Diagnosis

The symptoms of DSMA1 typically manifest shortly after birth or within the first few months of life. The primary features include severe muscle weakness and atrophy, particularly in the distal limbs. Affected infants may also experience difficulty breathing due to weakness of the respiratory muscles, leading to respiratory distress. Other symptoms can include poor feeding, failure to thrive, and in some cases, vocal cord paralysis.

Diagnosis of DSMA1 is based on clinical examination, family history, and genetic testing to identify mutations in the IGHMBP2 gene. Electromyography (EMG) and nerve conduction studies may also be conducted to assess the extent of muscle and nerve involvement.

Treatment and Management

There is currently no cure for DSMA1, and treatment focuses on managing symptoms and improving quality of life. Respiratory support may be necessary for those with respiratory distress, including the use of ventilators or bi-level positive airway pressure (BiPAP) machines. Physical therapy and occupational therapy can help maintain muscle function and mobility for as long as possible. Nutritional support is also important, especially for those with feeding difficulties.

Prognosis

The prognosis for individuals with DSMA1 varies. The disease is progressive, and respiratory failure is a major cause of morbidity and mortality in early childhood. However, with appropriate medical and supportive care, some individuals with DSMA1 can survive into adolescence or longer.

Research

Research into DSMA1 is ongoing, with studies focusing on understanding the molecular mechanisms underlying the disease and developing potential treatments. Gene therapy and molecular therapies targeting the specific genetic mutations or compensating for the lost function of the IGHMBP2 protein are areas of interest.