Bethlem myopathy is an

autosomal dominant In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and t ...

myopathy In medicine, myopathy is a disease of the muscle in which the muscle fibers do not function properly. This results in muscular weakness. ''Myopathy'' means muscle disease (Greek : myo- ''muscle'' + patheia '' -pathy'' : ''suffering''). This meani ...

, classified as a

congenital A birth defect, also known as a congenital disorder, is an abnormal condition that is present at birth regardless of its cause. Birth defects may result in disabilities that may be physical, intellectual, or developmental. The disabilities can ...

form of

muscular dystrophy Muscular dystrophies (MD) are a genetically and clinically heterogeneous group of rare neuromuscular diseases that cause progressive weakness and breakdown of skeletal muscles over time. The disorders differ as to which muscles are primarily affe ...

, that is caused by a

mutation In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mi ...

in one of the three

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...

s coding for type VI

collagen Collagen () is the main structural protein in the extracellular matrix found in the body's various connective tissues. As the main component of connective tissue, it is the most abundant protein in mammals, making up from 25% to 35% of the whole ...

. These include

COL6A1 Collagen alpha-1(VI) chain is a protein that in humans is encoded by the ''COL6A1'' gene. Function The collagens are a superfamily of proteins that play a role in maintaining the integrity of various tissues. Collagens are extracellular matrix ...

COL6A2 Collagen alpha-2(VI) chain is a protein that in humans is encoded by the ''COL6A2'' gene. Function This gene encodes one of the three alpha chains of type VI collagen, a beaded filament collagen found in most connective tissues. The product o ...

, and

COL6A3 Collagen alpha-3(VI) chain is a protein that in humans is encoded by the ''COL6A3'' gene. This protein is an alpha chain of type VI collagen that aids in microfibril formation. As part of type VI collagen, this protein has been implicated in Bethl ...

. Gower's sign,

tiptoe Tiptoe (tiptoes or tippy toes) describes the human body posture and locomotion of removing the heel(s) of one or both feet from the ground. The term is mostly used colloquially when the weight is placed on the balls of the feet rather than lit ...

-walking and

contracture In pathology, a contracture is a permanent shortening of a muscle or joint. It is usually in response to prolonged hypertonic spasticity in a concentrated muscle area, such as is seen in the tightest muscles of people with conditions like spasti ...

s of the joints (especially the fingers) are typical signs and symptoms of the disease. Bethlem myopathy could be diagnosed based on clinical examinations and laboratory tests may be recommended. Currently there is no cure for the disease and

symptomatic treatment Symptomatic treatment, supportive care, supportive therapy, or palliative treatment is any medical therapy of a disease that only affects its symptoms, not the underlying cause. It is usually aimed at reducing the signs and symptoms for the comfor ...

is used to relieve symptoms and improve quality of life. Bethlem myopathy affects about 1 in 200,000 people.

Signs and symptoms

The onset of this disease can begin even before birth but is more commonly in childhood or later into adult life. The progression is slow, with symptoms of weakness and walking difficulties sometimes not presenting until middle age. 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

Contracture In pathology, a contracture is a permanent shortening of a muscle or joint. It is usually in response to prolonged hypertonic spasticity in a concentrated muscle area, such as is seen in the tightest muscles of people with conditions like spasti ...

s of the fingers are a typical symptom of Bethlem myopathy but not of the related Ullrich's myopathy (which does include contractures of arms and legs, as does Bethlem myopathy). Serum

creatine kinase Creatine kinase (CK), also known as creatine phosphokinase (CPK) or phosphocreatine kinase, is an enzyme () expressed by various tissues and cell types. CK catalyses the conversion of creatine and uses adenosine triphosphate (ATP) to create phosp ...

is elevated in Bethlem myopathy, as there is ongoing muscle cell death. Patients with Bethlem myopathy may expect a normal life span and continued mobility into adulthood.

Diagnosis

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 A biopsy is a medical test commonly performed by a surgeon, interventional radiologist, or an interventional cardiologist. The process involves extraction of sample cells or tissues for examination to determine the presence or extent of a diseas ...

MRI Magnetic resonance imaging (MRI) is a medical imaging technique used in radiology to form pictures of the anatomy and the physiological processes of the body. MRI scanners use strong magnetic fields, magnetic field gradients, and radio waves ...

of the muscles,

electromyography Electromyography (EMG) is a technique for evaluating and recording the electrical activity produced by skeletal muscles. EMG is performed using an instrument called an electromyograph to produce a record called an electromyogram. An electromyog ...

(EMG) are the main testing methods of the disease. The diagnosis can be confirmed with genetic testing of the

, and

genes. Phenotypes of overlap between

Ullrich congenital muscular dystrophy Ullrich congenital muscular dystrophy is a form of congenital muscular dystrophy. It is associated with variants of type VI collagen, it is commonly associated with muscle weakness and respiratory problems, though cardiac issues are not associated ...

(UCMD) and Bethlem can be assumed. In the

differential diagnosis In healthcare, a differential diagnosis (abbreviated DDx) is a method of analysis of a patient's history and physical examination to arrive at the correct diagnosis. It involves distinguishing a particular disease or condition from others that p ...

of UCDM, even in patients without finger contractures, Bethlem myopathy could be considered.

Treatment

Currently there is no cure for the disease.

Symptomatic treatment Symptomatic treatment, supportive care, supportive therapy, or palliative treatment is any medical therapy of a disease that only affects its symptoms, not the underlying cause. It is usually aimed at reducing the signs and symptoms for the comfor ...

, which aims to relieve symptoms and improve quality of life is the main treatment method of Bethlem myopathy. It is believed that

physical therapy Physical therapy (PT), also known as physiotherapy, is one of the allied health professions. It is provided by physical therapists who promote, maintain, or restore health through physical examination, diagnosis, management, prognosis, patient ...

, stretching exercises,

orthoses Orthotics ( el, Ορθός, translit=ortho, lit=to straighten, to align) is a medical specialty that focuses on the design and application of orthoses, or braces. An is "an externally applied device used to influence the structural and functio ...

such as braces and

splints Splints is an ailment of the horse or pony, characterized by a hard, bony swelling, usually on the inside of a front leg, lying between the splint and cannon bone or on the splint bone itself. It may be "hot," meaning that it occurred recently an ...

, and

mobility aid A mobility aid is a device designed to assist walking or otherwise improve the mobility of people with a mobility impairment. There are various walking aids which can help people with impaired ability to walk, and wheelchairs or mobility scoote ...

s like a

walker Walker or The Walker may refer to: People *Walker (given name) *Walker (surname) *Walker (Brazilian footballer) (born 1982), Brazilian footballer Places In the United States *Walker, Arizona, in Yavapai County *Walker, Mono County, California * ...

wheelchair A wheelchair is a chair with wheels, used when walking is difficult or impossible due to illness, injury, problems related to old age, or disability. These can include spinal cord injuries ( paraplegia, hemiplegia, and quadriplegia), cerebr ...

are beneficial to patient's condition. Surgical options could be considered in rare instances, in order to help with

joint contractures In pathology, a contracture is a permanent shortening of a muscle or joint. It is usually in response to prolonged hypertonic spasticity in a concentrated muscle area, such as is seen in the tightest muscles of people with conditions like spasti ...

scoliosis Scoliosis is a condition in which a person's spine has a sideways curve. The curve is usually "S"- or "C"-shaped over three dimensions. In some, the degree of curve is stable, while in others, it increases over time. Mild scoliosis does not t ...

. 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.

Epidemiology

According to a Japanese study from 2007 Bethlem myopathy affects about 1 in 200,000 people.Okada M ''et al'' (2007) Primary collagen VI deficiency is the second most common congenital muscular dystrophy in Japan. Neurolog 69:1035–1042 A 2009 study concerning the prevalence of genetic muscle disease in

Northern England Northern England, also known as the North of England, the North Country, or simply the North, is the northern area of England. It broadly corresponds to the former borders of Angle Northumbria, the Anglo-Scandinavian Kingdom of Jorvik, and the ...

estimated the prevalence of Bethlem myopathy to be at 0.77:100,000. Together with the UCMD it is believed to be underdiagnosed. Both conditions have been described in individuals from a variety of ethnic backgrounds.

References

External links

{{Collagen disease Autosomal dominant disorders Myoneural junction and neuromuscular diseases Collagen disease