Adult and adolescent onset muscular dystrophies: evaluation and diagnosis

Author(s): Edwardo Ramos, MD, Manuel F. Mas, MD, Fernando L. Sepúlveda, MD

Originally published:08/30/2013

Last updated:08/30/2013



Adult and adolescent onset muscular dystrophies (MDs) are a group of disorders affecting primarily structural muscle proteins that cause progressive muscle weakness and atrophy presenting during the second decade of life and beyond. Most are due to mutations in the genes responsible for giving the muscle structural support and homeostasis. Other organ systems can be affected in some of these conditions. They are organized by the pattern of weakness and inheritance. While in some cases a discrete mutation accounts for a specific clinical syndrome, increasingly it has been recognized that different mutations can cause a similar phenotypic expression, while a specific gene mutation can lead to different phenotypes. As a general rule, muscle dystrophies present with proximal and symmetric muscle weakness, though others present with distal or regional weakness (see below).1,2 Initially, conditions were named by their clinical presentation, such as limb-girdle MDs (LGMDs). As mutations and hereditary patterns (autosomal dominant, autosomal recessive) were discovered, they were divided into type 1 and 2 and later on subdivided further (1a,b, etc). They have also been classified by age of presentation (congenital MDs) or pattern of weakness (regional MDs, distal MDs). The dystrophinopathies (Duchenne and Becker) are typically discussed outside of these subcategories. Others include the dystrophic myotonias (myotonic dystrophies type 1 and 2), metabolic myopathies, non-dystrophic myotonias, channelopathies, and congenital myopathies, which are also inherited but are considered separate categories and clinically distinct.


Most MDs are inherited disorders, but spontaneous mutations can occur. These can be X-linked (Emery-Dreifuss, dystrophinopathies), autosomal dominant (some LGMDs and facioscapulohumeral MD) or autosomal recessive (other LGMDs). Careful history of family members must be a part of medical evaluation.

Epidemiology including risk factors and primary prevention

Facioscapulohumeral MD (FSHMD) has a prevalence of 5:100,000.1 Due to the numerous amounts of genetic variations of the LGMDs, prevalence is broad and ranges from 1:14,500 to 1:123,000.3 MDs are genetic disorders obtained by way of inheritance or spontaneous mutation. This makes identifying risk factors and providing primary prevention for patients difficult. Genetic counseling is available for parents to understand their genetic characteristics and risk of future offspring in presenting with MD.


In order for the skeletal muscle to function properly, it requires intact intracellular structural proteins, sarcolemma, glycoproteins and extracellular matrix. A mutation of any of these proteins can cause an LGMD syndrome. In the history of muscle disease, the first discovery was the identification of the mutation responsible for Duchenne/Becker muscular dystrophy. This protein was named dystrophin, and diseases resulting from mutations in dystrophin are termed dystrophinopathies. This opened the door for identification of other proteins and glycoproteins (calpain, dysferlin, sarcanoglycans, calveolin, telethonin, etc). Mutations of the genes for these proteins lead to clinical syndromes termed calpainopathies, dysferlinopathies, sarcoglycanopathies, thelethoninopathies, dystroglycanopathies and others. The exact relationship between certain mutations and clinical syndromes is being explored. The majority of these proteins seem to be related to structural integrity of the sarcolemma. In some cases, these proteins are important to tissues other than skeletal muscle. This leads to the manifestation of clinical features that involve the cardiac, pulmonary, gastrointestinal and central nervous systems.4

Disease progression including natural history, disease phases or stages, disease trajectory (clinical features and presentation over time)

Although there are several subtypes of adult-onset MDs, a general disease begins with strength loss and decreasing endurance. Patients may develop symptoms at different points in their life. Weakness is mostly in the pelvic and scapular region. Patients may experience falls, difficulty ascending stairs, exercise intolerance, muscle cramps, episodic weakness, focal wasting of muscle groups, contractures and breathing difficulties. 5,6

Specific secondary or associated conditions and complications

Although symptoms tend to be primarily neuromuscular in nature, MDs can have manifestations on additional organ systems. These vary depending on the genetic subtype and may include cardiomyopathy, depression, restrictive lung disease, scoliosis, contractures, and mental impairment.



A detailed family history is essential, as affected family members can confirm the inherited nature of the disease, as well as narrowing the differential diagnosis substantially based on the inheritance pattern. Most patients present with insidious weakness. Some may complain of fatigue and decreased endurance, though prominent fatiguability is more common in neuromuscular junction disorders. Proximal weakness may present as difficulty with overhead activities such as washing hair, hip flexor weakness as difficulty lifting legs in and out of the car, and quadriceps weakness with trouble getting out of chairs or going up or down stairs. Distal weakness can be seen in the distal or regional limb girdle dystrophies, which may present with complaints of dropping objects, wrist or foot drop. Other symptoms may include falls, exercise intolerance, muscle cramps and breathing difficulties, among others. Some patients may notice atrophy in affected muscles or scapular winging.5,6

Physical examination

Inspection should include assessing for scoliosis, kyposis, scapular winging and chest anomalies such as pectus excavatum. Facial muscles may show atrophy or weakness. Ptosis and extraocular involvement often indicatens a confounding diagnosis such as a neuromuscular junction disorder or mitochondrial myopathy. Pseudohypertrophy is helpful in diagnosing dystrophinopathies, and significant atrophy can be helpful in Myoshi and other myopathies. The presence of fasciculations can point to other neuromuscular issues such as motor neuron disease or multifocal motor neuropathy. Gait pattern can also give hints on the pattern of weakness (trendelenburg or flat-foot strike). The presence of contractures in particular joints can give significant clues to the ultimate type of MD, such as elbows flexors and cervical extensors contractures which are almost pathognomonic for Emery-Dreifuss MD. Examination must include other organ systems such as cardiaovascular, pulmonary and gastrointestinal.

Muscle strength evaluation should focus on the pattern of muscle weakness: proximal vs distal, symmetric vs asymmetric. Some conditions present asymmetric muscle weakness that can help in the diagnosis (FSHMD). Percussion or action myotonia can point to other diagnoses that may mimic LGMDs, such as myotonic dystrophies or channelopathies.5,6,7,8,9

Functional assessment

Functional assessment should be tailored to the different stages of the specific disease being evaluated. A great number of patients diagnosed with MD develop progressive weakness, thus hindering their ability to walk, propel a wheelchair, stand up from a chair or climb stairs. Cardiopulmonary impairments and weakness might also affect the patient’s endurance. The above-mentioned characteristics usually result in an inability to perform activities of daily living (ADLs) such as dressing, hygiene or grooming without assistance. Some types of MDs also present with cognitive impairments.10

Laboratory studies

Laboratory studies can confirm the suspected diagnosis. These can be divided into general and specific laboratory studies.

Muscle enzymes such as serum creatinine kinase (CK) and aldolase: these are usually elevated in MD. The degree of elevation is not consistent with disease severity. Some conditions may present with normal or moderately elevated CK (FSHD, EDMD). Others may present with markedly elevated CK levels (Myoshi myopathy). It is common to have elevated transaminases of muscle origin which may give the false impression of liver disease.5

Molecular genetic studies: These are available for some MD subtypes, yet do not always lead to diagnosis, as a single genotype can lead to multiple phenotypes and some mutations are of unclear significance. These are available for some LGMD syndromes, FSHMD, and Emery-Dreyfuss MD.11,12

Muscle Biopsy: vastus lateralis, triceps, biceps and posterior deltoid most commonly used. Typical Hematoxolin and Eosin findings include variable fiber size, hypercontracted (opaque) muscle fibers, myopathic grouping and muscle fiber degeneration and regeneration (early stages). Specific muscle proteins can be measured: dystrophin, some sarcoglycans and others and can be diagnostic. Also, immunofluorescence examination can be performed for specific muscle proteins.13


Magnetic resonance imaging (MRI) is used increasingly to determine distributions of muscle inflammation or dystrophic changes. Musculoskeletal ultrasound presents an emerging and cost-effective screening technique for detection of dystrophic changes in striated muscle, but is limited to the evaluation of superficial muscle groups and requires further research.14,15

Supplemental assessment tools

Electrodiagnostic studies have decreased in popularity and been replaced by DNA testing in some cases. In cases where DNA testing is too expensive or not available, this is a useful diagnostic tool. It can help differentiate between MD and motor neuron disease or neuromuscular junction disorders and other myopathies in some cases. Nerve conduction studies (NCS) are usually normal, unless there is a coexistent neuropathy. If the myopathy is severe enough, motor studies might show decreased compound muscle action potential (CMAP) amplitudes. Repetitive stimulation studies can assess for neuromuscular junction pathology that might mimic a myopathy.

The most important part of the study is needle electromyography (EMG). Usually one side of the body is sampled. This allows the electromyographer to assess which muscles show greater pathologic findings, thus helping guide the muscle biopsy to the same muscles on the contralateral side. Which side (or muscles) were spared of needle EMG testing should be noted so a biopsy could avoid those muscles and resulting needle artifact. The muscles most involved electrodiagnostically can be mentioned, as the same muscles on the other side would have the highest yield for biopsy. Evaluation should include both distal muscles, proximal muscles, and paraspinals of the upper and lower limb and thoracic paraspinals, as well as facial muscles if clinically involved. The myopathic process and muscle necrosis may cause functional denervation with resultant fibrillation potentials and positive sharp waves. Complex repetitive discharges can be seen as well. As with other myopathies, motor unit action potentials (MUAP) will typically show decreased duration and amplitude with increased polyphasicity. Chronic myopathies like adult onset MDs may have large MUAP, potentially confusing them with neuopathic conditions. Early (increased) MUAP recruitment is also evident at low force thresholds.16,17,18

Evaluation for cardiac pathology such as electrocardiograms, Holter monitoring, or echocardiogram help in establishing conduction defects, arrhythmias and cardiomyopathies associated with some MD’s. Pulmonary function tests can also be used for evaluation of decreased functional vital capacity.19,20

Early predictions of outcomes

After performing the initial work-up and establishing the correct diagnosis it is possible to educate the patient about the usual disease progression associated with his/her particular variation of MD. Because of varying degrees of penetration, the same disease in different family members may present and progress differently.6


Evaluation of the patient’s home, school or work should be performed to identify any possible barriers for participation. This includes stairs, having to walk long distances, uneven terrain and inaccessible bathroom facilities. Education regarding assistive devices and structure modifications such as ramps or railings should be performed. The patient’s driving capability, possible vehicle modifications, and alternative means of transport should be discussed.

Social role and social support system

Taking into consideration the patient’s limitations and disability, it is important to assess the support structure that friends and family members might provide. This structure is vital for ensuring proper care and adaptation to society, including transportation, employment and adaptive recreational activities. It is important to discuss what to expect in terms of disease progression, proper care or adaptations required.

Professional Issues

Evaluation by genetics specialists and subsequent counseling should be considered to discuss issues related to family planning and the implications of genetic testing on insurability and employment.








1. Hilton-Jones D. Myopathies in the adult patient. Medicine. 2012;40(10):558-565.

2. Tesi C, Hoffman E. Limb-girdle and congenital muscular dystrophies: current diagnostics, management, and emerging technologies. Curr Neurol Neurosci Rep. 2010;10(4):267-276.

3. Ferreira AF, Carvalho MS, Resende MB: Phenotypic and immunohistochemical characterization of sarcoglycanopathies. Clinics (Sao Paulo). 2011; 66(10):1713-1719.

4. Cohn R, Campbell K: Molecular basis of muscular dystrophies. Muscle Nerve. 2000; 23(10):1456-1471.

5. Wicklund M: Approaches to diseases of muscle. In Tawil R, Venance S (ed): Neuromuscular Disorders. Oxford, Eng: Wiley-Blackwell, 2011;9-14.

6. Norwood F, Visser M, Eymard B, et al. EFNS guideline on diagnosis and management of limb girdle muscular dystrophies. Eur J Neurol. 2007;14(12):1305-1312.

7. Bushby K, Norwood F, Straub V. The limb-girdle muscular dystrophies: diagnostic strategies. Biochim Biophys Acta. 2007;1772(2):238-242.

8. Bushby K. The limb-girdle muscular dystrophies-diagnostic guidelines. Eur J of Pediatr Neurol. 1999;3(2): 53-58.

9. Guglieri M, Bushby K. How to go about diagnosing and managing the limb-girdle muscular dystrophies. Neurol India. 2008;56(3):271-280.

10. D’Angelo MG, Bresolin N. Cognitive impairment in neuromuscular disorders. Muscle Nerve. 2006; 34(1):16-33.

11. Krajewski K, Shy M. Genetic testing in neuromuscular disease. Neurol Clin. 2004;22(3):481-508.

12. Greenberg SA, Walsh RJ. Molecular diagnosis of inheritable neuromuscular disorders. Part II: Application of genetic testing in neuromuscular disease. Muscle Nerve. 2005;31(4):431-451.

13. Jaradeh S, Ho H. Muscle, nerve and skin biopsy. Neurol Clin. 2004;22(3): 539-561.

14. Wattjes MP, Kley RA, Fischer D. Neuromuscular imaging in inherited muscle diseases. Eur Radiol. 2010;20(10):2447-2460.

15. Lovitt S, Marden F, Gundogdu B, et al. MRI in myopathy. Neurol Clin. 2004;22(3):509-538.

16. Barboi A, Barhaus P. Electrodiagnostic testing in neuromuscular disorders. Neurol Clin. 2004;22(3):619-641.

17. Preston DC, Shapiro BE. Myopathy. In: Preston DC, Shapiro BE, eds. Electromyography and Neuromuscular Disorders. 2nd ed. Philadelphia, PA: Elsevier; 2005:575.

18. Paganoni S, Amato A. Electrodiagnostic evaluation of myopathies. Phys Med Rehabil Clin N Am. 2013;24(1):193-207.

19. Bhakta D, Groh WJ. Cardiac function tests in neuromuscular diseases. Neurol Clin. 2004;22(3):591-617.

20. Goodwin FC, Muntoni F. Cardiac involvement in muscular dystrophies: molecular mechanisms. Muscle Nerve. 2005;32(5):577-588.


1. Amato A, Rusell JA. Neuromuscular Disorders. 1st ed.; New York City, New York. McGraw Hill; 2008.

Author Disclosures

Edwardo Ramos, MD
Nothing to Disclose

Manuel F. Mas, MD
Nothing to Disclose

Fernando L. Sepúlveda, MD
Nothing to Disclose

Related Articles