Which test confirms muscular dystrophy

Although in clinical observations, family history, muscle biopsy, and biochemical tests such as serum creatine kinase CK are still important tools for muscular dystrophy diagnosis, protein analysis and genetic study have an increasing importance in accurate establishing a diagnosis. For several years, until the discovery of other muscle proteins, dystrophin was the only protein studied to establish a diagnosis of muscular dystrophy. In the last 10 years, genes involved in various types of autosomal recessive muscular dystrophy LGMD as well as in congenital muscle dystrophies have been identified [ 16 , 17 , 18 ].

Differentiation between recessive muscle dystrophies is much more difficult to achieve on the basis of clinical criteria because of phenotypic variability [ 19 ], different starting age of onset [ 20 , 21 ], and a variable progression rate [ 22 ].

Identification of protein defect by immunohistochemistry and Western blotting allows firm and specific diagnosis in a wide variety of muscular dystrophies. However, while immunohistochemistry is very useful in identifying abnormal expression of primary protein deficiency, in genetically inherited recessive diseases, it is less useful for identifying primary defect in dominant diseases.

A complete examination should include evaluation of movement and difficulty controlling movement, gait abnormalities, muscle strength, and the presence of weakness pattern, and also identification of the muscle groups affected.

While the most common sign for different types of muscular dystrophy is the progressive muscle weakness, the other features like age of disease onset, muscle group affected, and rate of progression are specific for each type of muscular dystrophy [ 21 , 23 ]. Dystrophinopathies are recessive X-linked disorders caused by mutation in dystrophin gene [ 1 ]. Currently, they are recognized as a spectrum of disease with involvement of skeletal and cardiac muscle in different degree [ 24 ] and include Duchenne muscular dystrophy DMD and Becker muscular dystrophy BMD , involving mostly skeletal muscles, and DMD-associated dilated cardiomyopathy DCM , affecting preferentially the myocardium.

The clinical picture in males with dystrophinopathies ranges from mild to severe. The mild forms consist of high level of CK in serum and muscle cramps with myoglobinuria. In DMD, affected boys are clinically normal at birth. The onset of clinical features is in early childhood with delayed motor milestones, including delayed independent walking, with a mean age of walking of 18 months, and difficulties in standing up from the floor.

Patients with DMD have a waddling gait and difficulties in climbing stairs, running, jumping, and standing up due to proximal weakness [ 26 ]. They rise from a supine position using their arms Gower maneuver. The boys have hypertrophic and firm calf muscles [ 27 ].

The disease is rapidly progressive, at the age of 12 years, most boys being wheelchair bound [ 25 ]. Subsequently, the function of upper extremity will be lost, and, by the age of 14—15 years, cardiomyopathy is a common feature [ 26 ]; during the teenage years, the patients will require assisted ventilation [ 27 ].

Progressive cardiomyopathy and respiratory complications represent the most common causes of death in patients with DMD. Typically, the death occurs by 30 years of age, but currently the life expectancy of these patients has been improved through an improved management of cardiorespiratory function [ 28 ].

BMD is a milder form of muscular dystrophy characterized by skeletal muscle weakness with a later onset and a preservation of the gait for a longer period age of 40—50 years [ 25 ]. The patients present usually with high serum CK concentration, calf muscle hypertrophy, muscle cramps, myalgia, or with muscle weakness in the pelvic and shoulder girdles [ 26 ].

Cardiomyopathy is a common complication of BMD, the mean age of diagnosis being around 14, 6 years [ 28 ]. Heart failure represents the most common cause of death in BMD, at an age of mids [ 23 , 24 ]. EDMD is a muscular disorder with different inheritance patterns: X-linked recessive or autosomal dominant or autosomal recessive [ 25 , 26 ]. The clinical picture includes the classical triad: i early joint contractures, ii slowly progressive muscle weakness and wasting in humeroperoneal distribution upper arm, lower legs , and iii cardiac disease atrial-ventricular conduction anomalies, atrial arrhythmias [ 27 ].

Usually, the clinical presentation is characterized by Achilles contractures with toe walking in childhood. LGMDs represent a group of muscular conditions with autosomal dominant or autosomal recessive inheritance, characterized by a typical pattern of slowly progressive, proximal weakness which involves shoulder and pelvic girdle muscles [ 18 , 19 ].

Different subtypes of LGMDs have been described, with a wide clinical spectrum affecting various age groups. LGMDs1 forms have, generally, a later onset and a milder course compared with autosomal recessive forms [ 29 ]. The most affected muscle groups are proximal muscles, namely, the muscles of the shoulders, upper arms, pelvis, and thighs. The clinical picture can vary among different subtypes of FSHD, even within the same family [ 29 ].

The onset of clinical features can be at any age and worsen with time. The first symptoms include abnormal gait waddling gait, walking on the feet balls and difficulties in running and standing up [ 29 ]. The muscle weakness slowly progresses, and, in later stage of the disease, the patients may be wheelchair bound. Other clinical features include scapular wings, lumbar lordosis, scoliosis, calf muscle hypertrophy and joint stiffness, that restrict movement of the elbows, hips, knees, and ankles [ 30 ].

Cardiomyopathy was reported in some forms of LGMD, and some patients may present respiratory difficulties which can vary from mild to severe. In some rare forms of LGMD, intellectual disability has been reported [ 31 ].

FSHD is a genetic muscular disorder with autosomal dominant inheritance and a late onset; the disease has a slow progression and a high degree of phenotypic variability and side-to-side asymmetry [ 30 ]. The muscle weakness involves initial, facial, scapular, and proximal limb muscles mimetic muscles, serratus anterior, rhomboid muscles, biceps, and triceps [ 21 ]. The most frequent initial symptom is the inability to lift arms over shoulder height. Then, the weakness progress to lower limbs, typically the distal musculature first tibialis anterior and gastrocnemius , and later more proximal muscles quadriceps and hamstrings and the pelvic girdle are involved [ 21 ].

The abdominal and paraspinal muscles can be affected, causing an exaggerated lumbar lordosis or camptocormia bent spine syndrome [ 22 ]. Pectus excavatum is another common feature in FSHD [ 22 ]. It is present mostly in patients with pelvic girdle weakness who are wheelchair bound or with a marked paraspinal involvement or kyphoscoliosis. Cardiac involvement is not common in FSHD.

Some extramuscular manifestations have been described in patients with FSHD, almost always in the cases with the smallest number of residual D4Z4 units. They include retinal vascular changes peripheral telangiectasia ; Coats disease, a severe retinal vasculopathy characterized by aneurysmal dilatations and exudation, which can cause retinal detachment or blindness; loss of high-frequency hearing, usually asymptomatic; hearing loss; and intellectual disability and seizures in infants with FSHD [ 32 , 33 ].

A careful, complete, and thorough clinical examination along with laboratory investigations provides more information necessary for management of patients with muscular dystrophy, differentiates between the type of muscular dystrophy, and directs to subsequent analyses.

When a muscular dystrophy is suspected, blood enzyme test and a variety of laboratory test can be used for confirmation of clinical diagnosis.

The blood serum samples are used to determine the level of specific enzymes known to have a high blood serum levels when a dystrophic process is present: Creatine kinase CK also known as creatine phosphokinase CPK , an intracellular enzyme found with relative predominance in skeletal muscle, is considered as the most specific and sensitive marker of muscle disease.

Elevated level of CK could suggest a muscle disease before symptoms of muscular dystrophy become evident [ 33 , 34 ]. In early stages of the muscle disease, CK levels are 20— times greater than normal levels and tend to decrease with the muscle damage [ 15 ]. Recent studies show that losses of lung function in DMD patients determine the high level of CK in blood serum [ 35 ]. The level of CK has been found higher in other types of MD like limb-girdle muscular dystrophy LGMD [ 17 ] and could serve as useful indicator being able to discriminate between autosomal recessive and dominant types of LGMD, knowing that CK level recessive types of MD are higher than dominant ones.

It is interesting to note that not all cases of MD show a high level of CK. For example, in Ullrich congenital muscular dystrophy, Emery-Dreifuss muscular dystrophy, and Bethlem myopathy, the level of CK may be normal or slightly increased [ 22 ].

Aldolase, transaminases alanine aminotransferase ALT and aspartate aminotransferase AST , and lactate dehydrogenase LDH are other muscle enzymes also reported with a rise level in blood serum [ 18 ] when a muscular dystrophy is suspected. Also, from the blood collected on anticoagulant EDTA , total genomic DNA is isolated for further genetic tests used to confirm the diagnosis.

Other laboratory tests like electromyography, magnetic resonance imaging MRI , combined with muscle biopsy, and genetic tests contribute for toward a diagnosis. The assessment of skeletal muscle biopsy is an essential procedure for an accurate diagnosis when a muscle disease is suspected, providing evidence of pathological changes in muscle and guides for appropriate tests.

Even though the muscle biopsy is a highly invasive procedure, the data gained from it has the utmost importance for histopathological diagnosis and is an essential component in the diagnosis of muscle disorders that could identify the cause of the disease process and distinguish between different types of muscular dystrophy. In the end phases of the disease, the fibers are replaced by adipose tissue [ 36 ].

Histopathological changes differ widely in severity among the types of muscular dystrophy, as well as among allelic variants of the same genotype. Also, some features are specific for each type of muscular dystrophy. With all signs, none of the specific forms of muscular dystrophy can be diagnosed just based only on histological analysis.

Also, the muscle biopsy analysis can not only denote the specific genetic cause of the disease but can also provide clues for further investigation. In combination with protein analysis, the genetic investigations can provide an accurate diagnosis. The study of muscle protein expression is important for diagnosis, for genotype-phenotype correlations, and to identify possible genetic defect [ 37 , 38 , 39 ]. Both methods use labeled antibodies for a specific muscle protein involved in a type of muscular dystrophy.

In the past, the diagnosis of muscular dystrophy consisted only on clinical assessment, serum CK levels , and histological investigations of muscle biopsy [ 41 , 42 ]. The discovery in of the first muscle protein involved in a type of muscular dystrophy, dystrophin [ 43 ], has later led to the identification of the dystrophin-associated protein complex DAPC [ 44 ] and other additional proteins from the muscle cytosol calpain 3, TRIM32 [ 45 ], from extracellular matrix a2-laminin, collagen VI from the sarcomere telethonin, myotilin, titin, nebulin [ 46 ].

Each of these proteins is involved in a type of muscular dystrophy; so far over 40 types of muscular dystrophy are known [ 47 ]. A number of other tests can be used to find out more about the spread and extent of any muscle damage. This will help your doctor to identify or confirm which type of MD you have. Treatment can then be directed where it's most needed. Some tests include:. Once the doctor — usually a geneticist or neurologist — has an idea about what type of MD may be affecting you or your child, they may arrange genetic testing to look into this.

Genetic testing is simpler for some types of muscle conditions, so it may be arranged at an early stage if a specific condition is suspected, or after many other tests if it's more difficult to diagnose. There are many different genes that could potentially be responsible for MD, so it would be expensive and time-consuming to test them all.

However, genetic testing can sometimes confirm a diagnosis. For example, if you're diagnosed with Duchenne MD, tests can be carried out to check for a mutation in the dystrophin gene, because mutations in this gene are directly responsible for the condition. Genetic testing can also be used to identify carriers of MD and to perform prenatal diagnosis when a foetus is diagnosed before the baby is born. Page last reviewed: 20 July Next review due: 20 July Diagnosis will involve some or all of the following stages: investigating any symptoms discussing any family history of MD physical examination blood tests electrical tests on the nerves and muscles a muscle biopsy where a sample of tissue is removed for testing In the first instance, see a GP if you or your child have symptoms like muscle weakness or mobility problems.

Investigating symptoms The GP will need to know about any symptoms of MD that you or your child have noticed and when they began to appear. For example, you or your child may be: finding it difficult to climb the stairs unable to play sports as you used to finding it difficult to lift objects Identifying when symptoms first appeared and determining which muscles are affected is particularly useful in helping to diagnose different types of MD.

This is where a child stands up by: facing the floor placing their feet wide apart lifting their bottom first using their hands to "walk up" their legs by first placing their hands on their knees and then on their thighs See a GP if you think your child may have MD.

The GP will look at the following when they examine your child: the way your child stands the way your child walks — children with Duchenne MD often have a "waddling" style of walking; later on, they may stand and walk on the front part of their foot, with their heels off the ground whether your child has an exaggerated inward curve of their lower back — the medical term for this is lordosis, although it's sometimes called "sway back" whether your child has a sideways curvature of their spine, known as scoliosis whether your child's calves and other leg muscles look large compared with other muscles Family history If there's a history of MD in your family, it's important to discuss it with your GP.

Blood tests A sample of blood may be taken from a vein in your or your child's arm to test it for creatine kinase a protein usually found in muscle fibres.

Muscle biopsy A muscle biopsy involves removing a small sample of muscle tissue through a small cut incision , or using a hollow needle, so it can be examined under a microscope and tested for proteins.

Other tests A number of other tests can be used to find out more about the spread and extent of any muscle damage. Some tests include: Nerve conduction studies and electromyography EMG — tests used to examine the electrical activity in nerves and muscles at rest and when the muscles are contracting.

Skip to main content. Search MDA. Search Donate. Diagnosis In diagnosing any form of muscular dystrophy, a doctor usually begins by taking a patient and family history and performing a physical examination. CK and other enzyme levels Early in the diagnostic process, doctors often order a blood test called a CK level. Genetic testing Genetic testing involves analyzing the DNA of any cells usually blood cells are used to see whether there is a mutation in the dystrophin gene, and if so, exactly where it occurs.

Muscle biopsy To obtain more information, a doctor may order a muscle biopsy , the surgical removal of a small sample of muscle from the patient. Becker-type muscular dystrophy. Muscle Nerve Improved diagnosis of Becker muscular dystrophy by dystrophin testing. Neurology Looking for more information, support or ways to get involved?

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