Collagen VI-related dystrophy is a group of disorders that affect skeletal muscles (which are the muscles used for movement) and connective tissue (which provides strength and flexibility to the skin, joints, and other structures throughout the body). Most affected individuals have muscle weakness and joint deformities called contractures that restrict movement of the affected joints and worsen over time. Researchers have described several forms of collagen VI-related dystrophy, which range in severity: Bethlem muscular dystrophy is the mildest, an intermediate form is moderate in severity, and Ullrich congenital muscular dystrophy is the most severe.

Bethlem muscular dystrophy (also known as Bethlem myopathy) and Ulrich muscular dystrophy exist on a spectrum in terms of severity and prognosis of disease. Individuals with collagen VI-related dystrophy often have signs and symptoms of multiple forms of this condition, so it can be difficult to assign a specific diagnosis. The overlap in disease features, in addition to their common cause, is why these once separate conditions are now considered part of the same disease spectrum (source: Medlineplus.gov).

Learn more about Bethlem myopathy.

Learn more about Ulrich muscular dystrophy.

Progression of the disease largely depends on where an affected person sits on the spectrum of disease severity (between the milder Bethlem myopathy, the more severe Ulrich muscular dystrophy, or somewhere in between). Two individuals both diagnosed with a Collagen VI-related muscular dystrophy can have very different disease progressions, even if they have the same change at their genetic/DNA level. In almost all cases, weakening of the muscles, development of contractures (a fixed tightening of muscles that prevents normal movement of the associated joint), and decreased respiratory capacity are involved.

People on the more mild end of the spectrum (previously and sometimes referred to as Bethlem muscular dystrophy) usually have low muscle tone (hypotonia) in infancy. Muscle weakness can begin at any age but often appears in childhood to early adulthood. The muscle weakness is slowly progressive, with about two-thirds of affected individuals over age 50 needing walking assistance, particularly when outdoors. Affected individuals usually develop contractures by adulthood, typically in their fingers, elbows, shoulders, and ankles. Older individuals may develop weakness in respiratory muscles, which can cause breathing problems. Some people with this mild form of collagen VI-related dystrophy have skin abnormalities, including small bumps called follicular hyperkeratosis on the arms and legs; soft, velvety skin on the palms of the hands and soles of the feet; and abnormal wound healing that creates shallow scars.

The intermediate form of collagen VI-related dystrophy is characterized by muscle weakness that begins in infancy. Affected children are able to walk, although walking becomes increasingly difficult starting in early adulthood. They develop contractures in their fingers, elbows, shoulders, and ankles in childhood. In some affected people, the respiratory muscles are weakened, requiring people to use a machine to help them breathe (mechanical ventilation), particularly during sleep. (See sleep support section below)

People born on the most severe end of the spectrum (previously and sometimes referred to as Ullrich congenital muscular dystrophy) have severe muscle weakness beginning soon after birth. Some affected individuals are never able to walk and others can walk only with support. Those who can walk often lose the ability, usually in early adolescence. Individuals with Ullrich congenital muscular dystrophy develop contractures in their shoulders, elbows, hips, and knees, which further impair movement. Many individuals with this form of the condition have loose joints (joint laxity) in the fingers, wrists, toes, ankles, and other joints. Affected individuals need continuous mechanical ventilation to help them breathe while sleeping, and some may need it in the daytime. As with all forms of collagen vi-related muscular dystrophies some people present with follicular hyperkeratosis; soft, velvety skin on the palms and soles; and abnormal wound healing. (source: Medlineplus.gov)

Currently, there is no cure for Collagen VI-related muscular dystrophies but disease progression can be managed (though not completely stopped) through regular physiotherapy and medical specialist consultations.

Children and adults with Collagen VI-related muscular dystrophies should ideally be followed regularly in a specialist neuromuscular clinic (at least twice a year), with access to a multi-disciplinary team including physiotherapy, orthotic, respiratory, orthopedic, spinal and genetic specialists as needed (source: muscular dystrophy.uk). Many of those affected have also reported hydrotherapy, strength training, and consistent stretching exercises as particularly beneficial physical therapy activities. For some affected individuals, bracing, assistive devices (i.e., walker, wheelchair), or surgery may be helpful options to consider.

Additionally, scientists and organizations like the Collagen VI Research Fund (Col6Fund) are contributing to current research efforts to find genetic therapies and eventually a cure for Collagen VI diseases.