What is Werdnig-Hoffmann Disease?
Werdnig-Hoffmann disease is a specific kind of spinal muscular atrophy or SMA, which is a rare disease that affects the motor neurons, the nerve cells responsible for controlling our muscle movements. This type of disease is the most common form of SMA, affecting about 80% of people who have spinal muscular atrophy. There are four main types of SMA, and Werdnig-Hoffmann disease, also referred to as SMA1, is known to be the most severe.
Babies who have Werdnig-Hoffmann disease typically experience serious muscle weakness before they reach six months old. Symptoms include extreme motor weakness, poor muscle tone, and a lack of motor development, meaning they might struggle with movements and coordination.
Motor neuron diseases, including SMA, impact the anterior horn cells of the motor neurons, which are responsible for our voluntary muscle movements. These diseases, which also include conditions like amyotrophic lateral sclerosis (ALS) and progressive muscular atrophy (PMA), are generally very severe and unfortunately, there is no known cure. However, they don’t affect sensory nerves, which are responsible for our senses, such as touch and taste, so people with these conditions don’t have sensory symptoms.
Now, jumping back to SMA, there are four subtypes of this disease:
1. Werdnig-Hoffmann disease, also known as acute spinal muscular atrophy, is SMA1.
2. SMA2, also known as intermediate SMA and chronic infantile SMA, has less severe symptoms than SMA1. Individuals with this type can sit without support but struggle standing or walking. Symptoms typically appear during infancy.
3. SMA3, also known as Kugelberg-Welander disease, becomes noticeable after the first year of life. Initially, children can walk, but they later lose some motor abilities, which may result in poor balance, frequent falls, and scoliosis or curvature of the spine.
4. Individuals with SMA4 experience the least symptoms compared to the other forms and usually have a normal lifespan with normal motor development and mobility. Symptoms for this type generally start appearing after the age of 10.
What Causes Werdnig-Hoffmann Disease?
Werdnig-Hoffmann disease is a condition that you can inherit if both of your parents pass down the defective gene, which is a pattern known as autosomal recessive inheritance. The disease is known to be associated with abnormalities in the ‘survival motor neuron’ or SMN gene.
Interestingly, there are two types of SMN genes that have been identified, both found on chromosome 5, a part of your DNA. The first one is the SMN1 gene, and the second one is the SMN2 gene, located next to the first one.
It’s generally thought that SMN1 is likely the gene that causes the condition, while SMN2 seems to influence how severe the disease can be. In simple terms, having more copies of SMN2 often results in a less severe version of the disease.
In addition to this, other gene mutations have been identified that can also affect how severe the disease is. One such example is a mutation causing the deletion of the ‘neuronal apoptosis inhibitory protein’ or NAIP gene, which also plays a role in influencing the severity of the condition.
Risk Factors and Frequency for Werdnig-Hoffmann Disease
Werdnig-Hoffmann disease is a rare condition, affecting approximately one in every 10,000 newborns. It is the second most common disorder inherited in a pattern where both parents must carry the faulty gene. The disease impacts both men and women equally. Sadly, about half of those affected pass away before birth. Symptoms of this disease always show before a child reaches six months old.
Signs and Symptoms of Werdnig-Hoffmann Disease
Werdnig-Hoffmann disease is a condition that usually appears at birth, causing severe weakness and thinning of the limbs in newborns. Infants affected by this disease struggle with swallowing and breathing due to weakened muscles in these areas. Other muscles, specifically those in the brain stem, can also be affected. Despite these struggles, these babies won’t have any mental or brain dysfunction – they possess normal intelligence and learning abilities.
This disease is characterized by several distinctive symptoms:
- Very low muscle tone (hypotonia)
- Absence of deep tendon reflexes all over the body
- Extra flexibility in the joints due to low muscle tone
- Twitching of the tongue muscles (fasciculations), a common sign in motor neuron diseases
- Extreme difficulties in control head movement and in performing actions like sitting, standing, or walking
- Challenges in swallowing and breathing
- Poor sucking reflex
- Elevated risk of developing aspiration pneumonia because of weak muscles
For babies whose symptoms develop after birth, there will be a noticeable decline in motor skills, with the lower limbs being more affected than the upper limbs. However, the muscles controlling the movement of the eyes are usually spared.
Testing for Werdnig-Hoffmann Disease
The process to diagnose Werdnig-Hoffmann disease, a severe type of spinal muscular atrophy, starts with a thorough check-up and understanding of the patient’s medical and family history. If the disease has been present in the family before, there is a strong possibility that it might be the cause of the symptoms displayed.
To confirm the diagnosis, genetic tests can be conducted. These tests can be carried out either before birth (prenatally) or after birth (postnatally). If you are expecting a baby, there are procedures like chorionic villus sampling or amniocentesis, which involve taking samples of tissues from the womb, which can then be tested for the presence of the disease.
Werdnig-Hoffmann disease is linked to changes in a gene called the SMN gene. Molecular genetic tests can check for these changes. For this condition, either some or all of the SMN gene is missing.
In the past, doctors often used a test called electromyography (EMG) which is a way of checking the health of muscles and the nerves that control them by measuring electrical activity. However, now due to the easy accessibility of genetic tests, it’s no longer common to use EMG for the diagnosis of this condition.
Treatment Options for Werdnig-Hoffmann Disease
Werdnig-Hoffmann disease, also known as Spinal Muscular Atrophy (SMA), currently doesn’t have a cure. However, a certain medication called Nusinersen, which has been approved by the FDA, can help manage the disease in both adults and children. Nusinersen works to increase the production of a particular protein that this disease otherwise limits. This protein is essential for motor neuron health, which are cells responsible for muscle movement.
Even though a cure is not available, many treatments can help alleviate the symptoms. Phenylbutyrate, valproic acid, albuterol, and hydroxyurea may be used to control symptoms. However, these medications aren’t proven to stop the disease’s progression. The goal of the treatment is to manage the symptoms, which often require support in areas like feeding, breathing, and muscle weakness.
Children with the disease may struggle to eat properly and may even develop nutritional deficiencies or lung infections due to swallowing difficulties. A feeding tube, known as a percutaneous endoscopic gastrostomy (PEG) tube, can help ensure they get the nutrients they need.
Breathing difficulties are frequent since the disease affects the respiratory muscles. To support breathing, non-invasive ventilatory support like wearing a mask to help breathing, is used initially. As the disease progresses, a surgically inserted airway in the neck (tracheostomy) and a ventilator might be needed to help with breathing.
Physical issues like muscle weakness can be addressed through physical or occupational therapy. These therapies help with muscle stretching and strengthening as well as minimizing stiffening of the muscles and joints (contractures). If the child develops a sideways curvature of the spine (scoliosis), surgical procedures can help. Wearing braces might also provide additional support.
What else can Werdnig-Hoffmann Disease be?
Prader-Willi syndrome, congenital myasthenia gravis, congenital myopathies, infantile Pompe disease, congenital muscular dystrophy (CMD), arthrogryposis multiplex congenita, and adrenoleukodystrophy are all medical conditions that present with various symptoms. Here’s a brief overview of each condition:
- Prader-Willi syndrome is characterized by low muscle tone, short height, mental and developmental delays, excessive sleep, hormonal imbalances, inadequate sexual development, unstable body temperature, and underactive adrenal glands.
- Congenital myasthenia gravis happens due to a mutation in a particular gene, leading to fatigable weakness, especially in the eyes and cranial muscles.
- Congenital myopathies are slowly progressive muscle diseases causing muscle weakness and low muscle tone.
- Infantile Pompe disease is another muscle disease that causes low muscle tone, hearing issues, failure to thrive, and heart muscle involvement.
- Congenital muscular dystrophy (CMD) causes low muscle tone, stiff joints, and delayed motor skill development.
- Arthrogryposis multiplex congenita results in multiple joint contractions.
- Adrenoleukodystrophy presents with seizures, difficulty swallowing, hearing loss, and cognitive impairment.
What to expect with Werdnig-Hoffmann Disease
The outlook for Werdnig Hoffmann disease, also known as the most common genetic cause of infant mortality, is unfortunately quite bleak. The disease typically appears before an infant is 6 months old and gradually worsens over time. It is a condition that affects the muscles, causing them to deteriorate.
Often, this results in the early passing of those affected. Many patients do not survive past infancy or early childhood, frequently passing away by the age of 2 years.
Possible Complications When Diagnosed with Werdnig-Hoffmann Disease
Common problems related to bone and muscles, such as scoliosis (spinal curvature), joint stiffening, and ankylosis (abnormal bone fusion), can occur due to muscle weakness and waste. Specialists, such as physical and occupational therapists, can assist with these symptoms through therapy, surgery, or braces.
A serious lung infection, known as aspiration pneumonia, may occur due to weaknesses in the throat muscles.
In addition, difficulty with swallowing can lead to malnutrition, which is a frequent complication.
Here are some of these complications and solutions:
- Scoliosis, joint stiffening, and abnormal bone fusion due to muscle weakness and waste.
- Physical and occupational therapy, orthopedic surgery, or braces may help manage these issues.
- Aspiration pneumonia, a severe lung infection, can occur due to weaknesses in the throat muscles.
- Dietary problems like malnutrition are common due to swallowing difficulties.
Preventing Werdnig-Hoffmann Disease
Being told that a family member has Werdnig-Hoffmann disease can be challenging and distressing. This may feel like a lot to take in. It’s vital that families are given enough information to help manage the disease. This includes talking about what to expect, potential complications, and outcomes. Support groups can be useful to manage feelings of worry, frustration, loneliness, and sadness.
Moreover, loved ones should be made aware of the medical condition and given insights regarding the likely course of the disease. This understanding will allow them to effectively contribute to the planning of medical care and psychological support methods.
