Bethlem myopathy

Individual demonstrates lack of finger contractures, thus lack of Bethlem sign, by being able to make full contact of palms and fingers with elbows raised.

Bethlem myopathy is a slowly progressive muscle disease characterized predominantly by contractures, rigidity of the spine, skin abnormalities and proximal weakness.[7] Symptoms may present as early as infancy, with typical contractures and hyperlaxity of joints; however, in some patients, symptoms may go unnoticed until adolescence or adulthood.[7] Serum creatine kinase (CK) is usually normal to mildly elevated (<5×).[7]

Much like in this painting, Bethlem sign is an inability to make full contact of palms and fingers while elbows are raised, due to finger contractures.

Early symptoms include Gower's sign ("climbing" up the thighs with the hands when rising from the floor) and tiptoe-walking caused by the beginning of contractures.

Early on, there may be distal laxity (hypermobility), but all of those with Bethlem myopathy eventually develop multiple joint contractures: long finger flexors, wrists, elbows, hips, knees and ankles. There may also be scoliosis or rigid spine. Skin abnormalities are common, including keloid formation, ‘cigarette paper scarring’ [atrophic scarring] and follicular hyperkeratosis.[7]

'Bethlem sign' is the typical sign in Bethlem myopathy patients demonstrating long finger flexor contractures. With palms facing each other and with elbows raised, patients try to make full contact of one hand against the other, in what looks like the gesture of hands during prayer.[8]

In Bethlem myopathy 1, in the calf, one of the first signs is often a 'rim' of fatty infiltration between the soleus and gastrocnemius muscles.[9] In Bethlem myopathy 2, the only prominent finding on T1-weighted MR images (used to detect fatty infiltration) was atrophy of the rectus femoris muscles, with the pattern of muscle involvement correlated with disease severity.[9] Bethlem myopathy 2 also differs by including scapula winging, stooped posture or kyphosis (hunchback).[9]

The disease could be diagnosed based on a clinical examination, which identifies signs and symptoms generally associated with the people who have the condition. Additional laboratory tests may be recommended. Creatine kinase (CK) blood test results will generally be normal or only slightly elevated. Skin biopsy, MRI of the muscles, electromyography (EMG) are the main testing methods of the disease. The diagnosis can be confirmed with genetic testing of the COL6A1, COL6A2, COL6A3 and COL12A1 genes.[10][2]

Phenotypes of overlap between Ullrich congenital muscular dystrophy (UCMD) and Bethlem can be assumed. In the differential diagnosis of UCDM, even in patients without finger contractures, Bethlem myopathy could be considered.[11]

Ullrich congenital muscular dystrophy (UCMD) involves mutations on the same genes as Bethlem myopathy, but has a more severe presentation, with the ability to walk (ambulation) typically being lost between the ages of 5-15 years.[8]

The symptoms of Bethlem myopathy may overlap with other conditions including Emery–Dreifuss muscular dystrophy, congenital muscular dystrophies, limb girdle muscular dystrophies, FHL1-related myopathies and some forms of Ehlers–Danlos syndrome.[7]

Typical to Bethlem myopathy is the presence of multiple contractures.[7] Contractures can be caused by a variety of reasons, from disease to lifestyle (see Muscle contractures). If the patient lacks multiple contractures, as well as lacks other common symptoms of Bethlem myopathy, and in addition has muscular or exercise-induced (dynamic) symptoms which are not known to be associated with Bethlem myopathy, then other myopathies should be considered.

Currently there is no cure for the disease. Symptomatic treatment, which aims to relieve symptoms and improve quality of life is the main treatment method of Bethlem myopathy. It is believed that physical therapy, stretching exercises, orthoses such as braces and splints, and mobility aids like a walker or wheelchair are beneficial to patient's condition.[10]

Surgical options could be considered in rare instances, in order to help with joint contractures or scoliosis.[10] Contractures of the legs can be alleviated with heel-cord surgery followed by bracing and regular physical therapy. Repeated surgeries to lengthen the heel cords may be needed as the child grows to adulthood.[3]

According to a Japanese study from 2007 Bethlem myopathy 1 affects about 1 in 200,000 people.[5] A 2009 study concerning the prevalence of genetic muscle disease in Northern England estimated the prevalence of Bethlem myopathy 1 to be at 0.77:100,000.[12] Together with the UCMD it is believed to be underdiagnosed. Both conditions have been described in individuals from a variety of ethnic backgrounds.[13] Bethlem myopathy 2 affects less than 1 in 1,000,000 people.[6]