Becker muscular dystrophy

Muscle
Muscular dystrophies
Becker muscular dystrophy

Authors: Wesley Hiser, M.D., Jesse L. Kresak, M.D.

Topic Completed: 1 January 2018

Revised: 13 December 2019

Copyright: 2002-2018, PathologyOutlines.com, Inc.

PubMed Search: Becker muscular dystrophy [title] "loattrfree full text"[sb]

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Table of Contents

Cite this page: Hiser W. Becker muscular dystrophy. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/musclebeckermusculardystrophy.html. Accessed January 26th, 2020.

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 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

Pediatrics 2015;135:513, Neuromuscul Disord 2014;24:482, J Child Neurol 2001;16:870, Tidsskr Nor Laegeforen 2014;134:1361

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