Spinal muscular atrophy with respiratory distress (SMARD) is considered a type of spinal muscular atrophy (SMA), a rare genetic disorder that causes progressive muscle weakness and atrophy. Despite their similarities, SMA and SMARD are also very different. Here, we will explore SMARD, its causes, progress, and outlook.

What Is SMARD?

SMARD is sometimes known by other names. These include:

• Spinal muscular atrophy with respiratory distress type 1 (SMARD1)
• Distal spinal muscular atrophy type 1 (DSMA1)
• Distal hereditary motor neuropathy type 6
• Autosomal recessive distal spinal muscular atrophy 1s

SMARD is a rare form of SMA. In fact, it’s so rare that the exact prevalence rates are largely unknown. According to the National Organization for Rare Disorders, SMARD may affect approximately 1 percent of those diagnosed with early onset SMA, which itself affects about 8 out of 100,000 births.

Both SMA and SMARD are inherited neuromuscular diseases that involve degeneration of the motor neurons in the spinal cord in infants and young children. However, unlike SMA, SMARD is marked by diaphragmatic paralysis, or paralysis of the diaphragm. This paralysis leads to respiratory distress (difficulty breathing), a common and dangerous feature of SMARD.

Additionally, SMARD begins in more distal muscles (those farther from the center of the body) compared to SMA. SMARD is also caused by a different genetic mutation than the one that causes SMA.

Causes of SMARD

SMARD is caused by a very specific genetic mutation. This genetic mutation was discovered by Katja Grohmann and colleagues in 2001. It affects the gene that codes for immunoglobulin mu DNA binding protein 2 (IGHMBP2), found on a chromosome called 11q13. There are several mutations that can occur at a number of various exons (coding sections) of the IGHMBP2 gene.

The function of the protein made by the IGHMBP2 gene at a cellular level is not well understood. However, some research suggests the gene plays an important role in regulating RNA and separating double-stranded DNA structure into single strands (known as helicase activity). This helicase activity allows for duplication of DNA. The research specifically implicates helicase activity associated with ribosomes (cellular organs that regulate protein synthesis) in the development of SMARD. Although this research shows that SMARD is different from SMA, more studies are needed to understand exactly how the suppressed IGHMBP2 gene leads to SMARD and its symptoms.

Symptoms of SMARD

The onset of SMARD symptoms generally begins during infancy. Sometimes, problems begin in the neonatal environment (in the womb), which can lead to reduced fetal movements, premature birth, and low birth weight. Respiratory problems are the hallmark symptom of SMARD, but there are other symptoms as well. Early symptoms of SMARD in infants include:

• Weak cry
• Difficulty breathing
• Noisy breathing
• Difficulty feeding
• Recurrent pneumonia

Later, between the ages of six weeks and six months, the following respiratory symptoms may develop as paralysis of the diaphragm begins:

• Shortness of breath
• Progressive respiratory distress
• Tachypnea (abnormally rapid breathing)
• Respiratory failure (inability to breathe)

Following respiratory failure, muscle weakness usually starts in the lower limbs. Muscle weakness can progress to complete muscle and limb paralysis. Additionally, the following symptoms can occur:

• Loss of deep tendon reflexes
• Scoliosis (abnormal sideways curvature of the spine)
• Kyphosis (abnormal outward curvature of the spine)
• Loss of bladder control or bowel control
• Gastroesophageal reflux (acid reflux and spitting up)
• Irregular heartbeat
• High blood pressure
• Excessive sweating
• Deformities in the hands or feet, such as clubfoot
• Front half of the foot turning inward (metatarsus varus)
• Curved or bent fingers or toes
• Stiffness or limited range of motion in the hands, feet, and joints

Diagnosing SMARD

A diagnosis of SMARD usually occurs after a child has experienced respiratory failure and has been placed on a ventilation unit. Although symptoms can assist in diagnosing SMARD, they can be misleading and suggest that a respiratory disorder is occurring, leading to a misdiagnosis. Variations in how SMARD presents — such as a lack of diaphragm paralysis — can also complicate making a correct diagnosis. A definitive SMARD diagnosis requires genetic testing for mutations in the IGHMBP2 gene.

Treatment and Management of SMARD

Unfortunately, no effective treatments for SMARD exist. The life expectancy for someone living with SMARD is difficult to predict and depends on factors such as medical interventions. Care for SMARD typically consists of managing symptoms for as long as possible, such as with a tracheostomy to help with breathing, or palliative care to ease other symptoms. Gene correction or replacement of the mutated gene may one day prove to be the best option. The recent approval of a genetic therapy for SMA provides hope for the future of SMARD treatment.

Building a Community

By joining mySMAteam — the social network for people with spinal muscular atrophy and their loved ones — you can connect with others who understand life with spinal muscular atrophy. On mySMAteam, members come together to ask questions, give advice, and share their stories.

Are you living with or caring for someone with SMA or SMARD? Share your experience in the comments below, or start a conversation by posting on mySMAteam.