What Is Werdnig-Hoffmann Disease?

Werdnig-Hoffmann disease, also called spinal muscular atrophy type 1 (SMA1), is a genetic neuromuscular disorder. It affects the nerve cells controlling the voluntary muscles—the muscles under your conscious control that you can move at will. 

Symptoms of Werdnig-Hoffmann disease are apparent before age 6 months, sometimes as early as birth. This condition is caused by specific gene mutations and is inherited. 

Keep reading to learn more about Werdnig-Hoffman disease, including symptoms, how it is caused and diagnosed, treatment, and more.

SMA1 Symptoms

SMA1 is a type of spinal muscular atrophy (SMA). SMA generally causes muscles to become weak over time. Children with different types of SMA will have problems controlling head movement, sitting up, and walking. These conditions can also affect swallowing and breathing as the condition worsens.

The severity of SMA depends on which type a child has. A child with SMA may not be able to support their head or sit up without support. They may have problems controlling their arms and legs and difficulties with swallowing. There is no cure for any type of SMA, but treatments can improve symptoms and help a child live longer.

SMA1 is considered severe because it affects the muscles that control breathing. Many children with the condition don’t live past age 2 because of breathing issues. Babies with SMA1 are very weak in the early months and have problems with feeding. Cognitive, mental, and emotional development are generally normal in SMA1.

Additional symptoms of SMA1 include:

• Muscle weakness
• Muscle twitching
• Changes in the shape of limbs due to muscle weakness
• Lack of ability to move the limbs
• Scoliosis—curvature of the spine over time
• Congenital (present at birth) bone fractures
• Thin ribs
• Difficulty with standing, walking, and sitting

Severe symptoms of SMA1 include:

• Aspiration pneumonia, which can lead to more severe conditions and death
• Heart defects, including ventricular septal defects—abnormal connections between the ventricles (lower chambers of the heart)
• Possible involvement of the autonomic nervous system—the part of the nervous system that supplies the internal organs

SMA is a degenerative condition, which means symptoms will worsen with time.

Causes

SMA types affect both babies and children. With SMA, there is a breakdown of the nerve cells of the brain and spinal cord, keeping the brain from sending the messages needed to control muscle movement. 

SMA1 is an inherited condition associated with abnormal genes. The abnormal gene associated with SMA1 and all types of SMA is the survival motor neuron (SMN). There have been two SMN genes identified with Werdnig-Hoffmann disease—SMN1 and SMN2.

SMN1 is believed to cause the disease and SMN2 is believed to affect disease severity. SMN2 copies can result in a milder form of the condition. Other gene mutations might also play a role in severity.

Diagnosis 

A diagnosis is generally made when a parent or caregiver notices symptoms of SMA1 in a baby or child. SMA might also be diagnosed during newborn screening. SMA was added to the federal Recommended Uniform Screening Panel (RUSP) newborn screening guidelines in 2018. 

When a parent or caregiver reports symptoms, a doctor will look at the children’s medical and family histories and perform a physical exam.

The medical professional will look for muscles that are weak or floppy and if there is twitching of the tongue. They will also test the child’s muscle reflexes. Your child’s doctor might request additional testing to help in making a diagnosis.

Testing for SMA might include:

• Bloodwork, including a blood test for an enzyme called creatine kinase (CK), which leaks from deteriorating muscles
• A muscle biopsy, used to check if the muscles are deteriorating or have characteristics unique to SMA1, such as muscle atrophy (muscle wasting), although muscle biopsies are no longer enough to confirm SMA
• Electromyography (EMG), to assess the health of muscles and nerve cells
• Molecular genetic testing, to detect changes in single genes
• Additional genetic testing, including amniocentesis or chorionic villus sampling during pregnancy to evaluate the fetus in the womb in families who had previous children with SMA1

The results of a newborn screening might show that your baby has SMA. However, a doctor will want to order more testing, including additional bloodwork, genetic testing, and a physical exam, to confirm the diagnosis. Additional testing can also help your child’s doctor understand the type of SMA and its severity.

Treatment

There is no cure for Werdnig-Hoffmann disease. However, treatment aims at managing symptoms of the condition. In addition, new gene replacement therapy options have recently been approved by the Food and Drug Administration (FDA), as well as disease-modifying therapies.

Zolgensma (onasemnogene abeparvovec-xioi) is a new type of gene therapy that involves an infusion to replace defective or missing SMN1 with a working copy. The new gene increases SMN protein levels, which might mean improved motor neuron function and increased survival. It is given to children younger than 2 years.

Disease-modifying therapies can help stimulate the production of SMN protein. Spinraza (nusinersen) has been approved for pediatric and adult patients. It is injected into the space around the spinal canal. Another medication—Evrysdi (risdiplam)—is prescribed for adults and children younger than 2 months and is taken daily by mouth.

Other treatment options include those that support feeding, breathing, and muscle weakness:

• Feeding support: Children who have feeding troubles can benefit from percutaneous endoscopic gastrostomy tubes for nutritional supplementation.
• Respiratory support: Some children may need non-invasive ventilation support when respiratory muscles are affected early on. As breathing troubles become worse, ventilator support and/or a tracheostomy might be needed as well.
• Muscle support: Physical and occupational therapies can help improve muscle strength; minimize tightening of muscles, tendons, and tissues; and reduce joint stiffness and shortening. Assistive devices, including orthopedic braces, walkers, crutches, and wheelchairs, can help to keep pressure off affected joints and muscles, and help with movement. Surgical procedures can help manage scoliosis.

Summary

Werdnig-Hoffmann disease (SMA1) affects the nerves controlling voluntary muscles. It is a genetic disease that is inherited. SMA1 symptoms include problems with controlling head movement, sitting up, and walking, progressing with symptoms of impaired breathing and feeding. The condition appears before the age of 6 months and is often fatal by age 2. There is no cure, but new treatments, including gene therapy, may provide hope for symptom relief.

A Word From Verywell 

For the most part, it is widely accepted that babies with Werdnig-Hoffman disease have a reduced lifespan, although this is improving. At some point, your family may need to consider end-of-life care options. Make sure you talk to the medical professionals early to help ensure the best possible care for your child as their condition progresses.

A diagnosis of SMA1 can be stressful and overwhelming. Be sure you look into SMA family education, counseling, and support groups. These resources can help you make sense of treatments, understand your child’s prognosis, be aware of complications, and manage stressors, anxiety, and depression. 

Many organizations can offer help and support to your family for dealing with and managing Werdnig-Hoffman disease, including Cure SMA, the SMA Foundation, and the Muscular Dystrophy Association.