Ullrich congenital muscular dystrophy (UCMD)

Ullrich congenital muscular dystrophy (UCMD) is a type of congenital muscular dystrophy (CMD), and part of the spectrum of conditions called collagen VI-related dystrophy (COL6-RD). UCMD causes progressive muscle weakness and joint stiffness typically from birth or early childhood. It can also cause breathing problems.

Bethlem myopathy is the mildest form of COL6-RD, while UCMD is the most severe. There is also an intermediate form between them. These conditions are caused by changes in the COL6A1, COL6A2 and COL6A3 genes, which help make a protein called collagen type VI.

The first signs of UCMD may be seen at birth or are usually evident within the first year of life. These include poor head control and delays in reaching motor milestones such as sitting unaided, crawling, or walking. Failure to gain weight and grow at the expected rate are also often early symptoms. The severity of symptoms at onset and progression varies amongst those affected and depends on the specific change in the COL6 genes. Initial symptoms could be subtle and go unnoticed, and the diagnosis may not be made until infancy or childhood.

Muscle weakness

Muscle weakness is often noticeable soon after birth. Various muscle groups are affected, including the arms, legs, core, and breathing muscles. The condition is expected to be slowly progressive.

The severity of weakness can vary greatly. Some children with a more intermediate form may learn to walk but later lose this ability, while those with UCMD at the most severe end of the spectrum may never be able to walk on their own.

Joints and spine

People with UCMD typically develop significant stiffness in the joints, known as contractures. This is where the tendons in the muscle tighten up and limit the range of movement, affecting mobility and fine motor skills (coordination of small muscles in the fingers and hands for activities like brushing your teeth). These may be present at birth and can affect the hips, knees, and elbows. Changes in the hip joints can result in dislocation in a child’s hips. At first, there may be significant joint flexibility (hyperlaxity) particularly in the hands and feet, with these joints stiffening up later in life.

Most children with UCMD develop scoliosis, where the spine curves to the side. It’s important to monitor the spine in a multi-disciplinary specialist clinic, where the team can consider options to improve posture and slow the progression of the curvature.

Respiratory

Breathing problems can occur because of weakness in the respiratory muscles, including the diaphragm. This can start at an early age so children and young people with UCMD should be reviewed and monitored in a specialist clinic. They may have frequent chest infections and breathing problems during sleep. Overnight breathing problems may result in symptoms of daytime sleepiness, morning headaches, poor appetite, weight loss, and increased fatigue.

Feeding difficulties

Children with UCMD often have difficulty feeding. This can result in long mealtimes and failure to gain weight in the first few years of life. Issues with nutrition can continue into adulthood and require monitoring.

Skin abnormalities

Cuts and injuries to the skin may heal slowly and leave thick, raised scars called keloid scars. Scars can happen after surgical procedures, injuries, or pressure sores caused by prolonged immobility. Skin on the arms and legs may feel rough or bumpy (hyperkeratosis pilaris). This happens because the skin contains collagen VI. Taking steps to prevent injuries and skin damage where possible is important.

Genetic changes

UCMD is caused by changes in one of the three genes that produce the collagen VI protein – COL6A1, COL6A2, or COL6A3. Changes may be to one or sometimes both copies of the COL6 gene. Collagen VI proteins form supportive networks around our muscle cells and act like scaffolds to hold and support them. When collagen VI is faulty or there isn’t enough of it, the muscle cells are not supported properly. Over time, this leads to muscle weakness and damage.

Inheritance

UCMD is usually inherited in an autosomal recessive pattern, which means that a person needs to inherit two changed copies of the gene, one from each parent, to develop the condition. However, there are some cases of UCMD that follow an autosomal dominant pattern, where a person only needs to inherit one changed gene from one parent to develop the condition. In rare cases, UCMD can also occur with no family history of the condition or evidence that parents carry a change on the COL6 gene.

For more information, see our inheritance and genetics page.

UCMD is usually suspected from a person’s medical history and diagnosed with a clinical assessment and genetic testing. A GP or paediatrician can refer to a neurologist for specialist investigations and testing. A neurologist is a doctor who specialises in conditions that affect the muscles and nervous system.

A neurologist will generally use a combination of:

• Physical examination and family history
• Muscle imaging, such as ultrasound of MRI, to look for specific changes linked to collagen VI-related conditions
• Genetic testing, using a blood sample, to check for changes in the COL6A1, COL6A2, or COL6A3 genes
• Muscle biopsy, where a small muscle sample is taken and examined under a microscope for changes in the appearance and quantity of collagen VI proteins
• Skin biopsy, which can be done using a local unaesthetic to examine the amount of collagen

Clinical symptoms and low levels or absence of collagen VI protein strongly suggest the possibility of UCMD, but the diagnosis is confirmed with genetic testing. This uses a blood sample to check for specific changes in one of the collagen VI genes (COL6A1, COL6A2, and COL6A3).

For more information, see our diagnosis page.

A multi-disciplinary approach is important in not only managing the condition and symptoms but in improving wellbeing too. Symptoms and severity of UCMD can vary, and with this the care required.

Access to a healthcare team

It’s important to have access to a multi-disciplinary healthcare team. Usually, the lead professional will be a neurologist in a specialist neuromuscular clinic. If you do not have contact with a neurologist or specialist doctor, speak to your GP about getting access to one.

Exercise and physiotherapy

Physiotherapy can help to keep the muscles engaged and maintain range of motion as joint stiffness (contractures) develops. People with UCMD are encouraged to remain as physically active as possible. Moderate exercise, such as swimming and walking (when possible), are recommended. A physiotherapist is a healthcare professional who helps manage symptoms through movement, exercise, and manual therapy. They can put together a suitable exercise plan and stretching programme. To find out more about advice for adults, see exercising with a muscle wasting condition.

Children will need support from caregivers to guide them through exercises and provide encouragement. Physiotherapists and/or occupational therapists can also provide advice on orthotic devices, like splints, walking aids, and wheelchairs to improve independence when necessary.

Orthopaedics

Orthopaedic management refers to the treatment and care of bones, joints, and muscles and can help with contractures and scoliosis. This might include using splints, braces, and other tailored orthotic devices. In some cases, surgery may be needed to correct more severe joint contractures, for example releasing the Achilles tendon to improve foot and ankle posture. This can help with seating position and standing, although it does not strengthen weak muscles.

Spinal surgery may be recommended to realign the spine. Surgical treatment should be carefully considered and coordinated by a specialist multi-disciplinary team with experience in treating people with neuromuscular conditions. This is important because there are key considerations for anaesthesia, post-operative care, and rehabilitation. It’s important to discuss all the options and goals of treatment before making a decision.

Respiratory

Respiratory function and lung capacity should be monitored regularly by a specialist team. Lung function testing is usually done in sitting and lying positions. Overnight sleep studies may be recommended to assess breathing while sleeping and diagnose night-time breathing problems, which can be associated with low oxygen and high carbon dioxide levels while sleeping. This can cause symptoms of morning headaches, daytime fatigue, and weight loss. Difficulty coughing and clearing secretions or phlegm from the chest can increase the risk of frequent chest infections. Non-invasive ventilation (NIV) may be recommended to support breathing during sleep. Some people may need to use ventilation machines for periods during the day or when they have chest infections that make breathing more difficult. Other equipment, such as a cough assist machine, may be recommended to help clear secretions.