Advertisement
Advertisement
Table of Contents
Definition / general | Essential features | Terminology | ICD-10 coding | Epidemiology | Sites | Pathophysiology | Etiology | Clinical features | Diagnosis | Laboratory | Prognostic factors | Case reports | Treatment | Microscopic (histologic) description | Microscopic (histologic) images | Positive stains | Negative stains | Molecular / cytogenetics description | Differential diagnosis | Additional references | Board review question #1 | Board review answer #1Cite this page: Hiser, W. Becker muscular dystrophy. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/musclebeckermusculardystrophy.html. Accessed May 24th, 2018.
Definition / general
- Muscular dystrophy caused by dystrophin (DMD) gene mutations on chromosome Xp21, leading to decreased / altered dystrophin protein expression
- Variable clinical course but progressive proximal weakness typically begins in childhood and leads to loss of ambulation in early adulthood
Essential features
- Closely related to Duchenne muscular dystrophy (DMD), in which dystrophin mutations lead to complete or near complete absence of dystrophin protein expression
- Mutations in Becker muscular dystrophy (BMD) lead to a truncated dystrophin protein with differing degrees of functionality and expression
- Histologic findings similar to DMD with myofiber size variation, nonspecific myofiber regenerative changes and fibrosis / fatty replacement late in the disease course
Terminology
- Named for the German physician, Peter Emil Becker, who first described the entity in the 1950's
- The term "dystrophinopathy" refers to both Duchenne and Becker muscular dystrophies
ICD-10 coding
- G71.0: muscular distrophy
Epidemiology
- Almost exclusively in males due to X linked inheritance
- Prevalence of 24 per 1 million males (Yachnis: Neuropathology - a Volume in the High Yield Pathology, 1st Edition, 2014)
Sites
- Weakness is most pronounced proximally and typically involves lower extremities to a greater degree than upper extremities (Yachnis: Neuropathology - a Volume in the High Yield Pathology, 1st Edition, 2014)
Pathophysiology
- Mutations in the DMD gene lead to reduced production of a truncated dystrophin protein which maintains partial functionality
- Dystrophin is a structural protein involved in linking the cytoskeleton with the extracellular matrix (Pediatr Clin North Am 2015;62:723)
Etiology
- X linked inherited disease caused by dystrophin gene mutations
- Up to 1/3 of cases arise de novo (Pediatr Clin North Am 2015;62:723)
Clinical features
- Significant variation in clinical presentation but patients typically present with muscle weakness during childhood
- About half of patients exhibit muscle weakness by the age of 10 (Pediatr Clin North Am 2015;62:723)
- Muscle weakness is most prominent proximally, typically in a limb girdle distribution
- Ability to jump may be preserved in some patients
- Cramping with strenuous physical activity
- Ambulation typically lost by third decade but may be retained far into adulthood (Pediatr Clin North Am 2015;62:723)
- Pseudohypertrophy of calf muscles
- Cardiomyopathies common
- Intellectual impairment is not typically seen
- Women who are carriers usually do not exhibit symptoms but may be susceptible to cardiomyopathies
Diagnosis
- Relies on clinical features in combination with genetic testing
- Muscle biopsy is less frequently performed but is useful for assessment of dystrophin expression (Pediatr Clin North Am 2015;62:723)
Laboratory
- Creatine kinase (CK) is significantly elevated but not to the degree seen in DMD
- Peak CK levels are usually found around 10 - 15 years of age
- ALT / AST may be elevated
- Can see occasional myoglobinuria following strenuous activity (Pediatr Clin North Am 2015;62:723)
Prognostic factors
- Extremely variable prognosis
- Some patients have course similar to DMD, while others experience only mild muscle weakness without significant loss of function
Case reports
- 9 year old boy with Becker muscular dystrophy with epilepsy and dysgnosia induced by duplication mutation of Dystrophin gene (BMC Neurol 2016;16:255)
- 13 year old boy with a mutation in DMD causing Becker muscular dystrophy associated with intellectual disability (J Dev Behav Pediatr 2016;37:239)
- 18 year old man with a case of Becker muscular dystrophy with early manifestation of cardiomyopathy (Korean J Pediatr 2012;55:350)
- 26 year old man with a case of refractory heart failure in Becker muscular dystrophy improved with corticosteroid therapy (Int Heart J 2016;57:640)
Treatment
- No curative treatment
- Supportive therapy including intense physical therapy
- Corticosteroids may be used in severe cases of BMD to improve muscle function and strength and may reduce scoliosis and severe cardiorespiratory complications
- Numerous clinical trials for gene therapy are currently in progress
Microscopic (histologic) description
- Typically less severe histologic findings than those seen in DMD
- Variation in myofiber size with small, atrophic fibers and large, rounded fibers
- Myofiber splitting with necrosis, phagocytosis and regeneration
- Increased internal nuclei - nonspecific finding seen in a number of myopathic processes; healthy muscle typically shows no more than 3 - 5% of fibers with internal nuclei
- Endomysial fibrosis and fatty replacement of muscle later in disease course
- Inflammation (T cells, macrophages) may be seen in association with myofiber necrosis (Yachnis: Neuropathology - a Volume in the High Yield Pathology, 1st Edition, 2014)
Microscopic (histologic) images
Images hosted on PathOut server:
Images contributed by Wesley Hiser, M.D.
Myopathic features
Becker dystrophin IHC
​Intact dystrophin IHC
Spectrin control
Positive stains
- Three antibodies which recognize epitopes in different domains are used to assess dystrophin expression (N-terminus, C-terminus and central rod domain)
- Sarcolemmal expression of dystrophin will be altered or reduced in BMD
- Spectrin is used as a control for assessing sarcolemmal membrane integrity (Yachnis: Neuropathology - a Volume in the High Yield Pathology, 1st Edition, 2014)
- NADH and SDH oxidative stains may show nonspecific myofibrillar changes such as moth eaten or whorled fibers
Negative stains
- Altered dystrophin expression may lead to absent staining for one or two dystrophin domains
Molecular / cytogenetics description
- Mutation of the dystrophin (DMD) gene on chromosome Xp21
- Mutations are in frame and do not shift the reading frame, resulting in internal deletions and duplications
- Stop codon is not produced as in Duchenne muscular dystrophy, so dystrophin protein is still produced (Pediatr Clin North Am 2015;62:723)
- Clinical features correlate with the functionality and amount of dystrophin
Differential diagnosis
- Congenital myopathies:
central core disease,
centronuclear myopathy,
nemaline myopathy
- Frequently have earlier onset, characteristic histologic findings and staining patterns
- Duchenne muscular dystrophy
- Earlier onset, severe clinical presentation
- Limb girdle muscular dystrophy
- Heterogeneous group of inherited muscular dystrophies which can clinically present like BMD / DMD and may require molecular testing to differentiate
Additional references
Board review question #1
Mutations in what gene are responsible for Becker muscular dystrophy?
- BKR
- DMD
- MTM1
- NEB
- RYR1
Board review answer #1
B. DMD
Advertisement
