Facioscapulohumeral Dystrophy

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Background

Facioscapulohumeral dystrophy (FSHD) is one of the most common types of muscular dystrophy.3133 It has distinct regional involvement and progression. FSHD is an autosomal dominant disorder in as many as 90% of affected patients. Landouzy and Dejerine first described FSHD in 1884. Tyler and Stephens described an extensive family from Utah in which 6 generations were affected. Walton and Nattrass established FSHD as a distinct muscular dystrophy with specific diagnostic criteria.

Pathophysiology

It is an autosomal dominant disease in 70-90% of patients and is sporadic in the rest. One of the FSHD genes has been localized to chromosome band 4q35, but the gene or genes that are affected in FSHD are still unknown. Patients with FSHD have a shorter Eco RI digestion fragment detected by the chromosome-4qter DNA marker p13E-11. About 2% of FSHD patients are not linked to the locus at 4q35.[1]

The probe p13E-11 identifies 2 polymorphic loci at 4q35 and 10q26. The Eco R1 fragment of 4q is composed of repetitive DNA sequences that are 3.3-kilobase (kb) Kpn I tandem repeats identified as D4Z4. In control subjects, the D4Z4 repeat consists of 11-100 KpnI units, each 3.3 kb, whereas in FSHD this is shortened; the shortened Eco RI fragment in FSHD is 1-10 units. Diagnostic difficulties arise as these fragments also may come from chromosome 10, as already described. 4-Type units are resistant to Bln I and 10-type units are resistant to Xap I. The combined use of EcoRI, BlnI, and XapI in pulsed-field gel electrophoresis–based DNA separation techniques allows detection of 4q fragments.

Disease mechanisms

The actual genetic defect in FSHD is unknown. Possible disease mechanisms include the following:

Epidemiology

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Frequency

United States

FSHD is the third most common muscular dystrophy. Estimated prevalence of FSHD is 1 case in 20,000 persons.[5]

Mortality/Morbidity

Most of the patients have normal life expectancy.

Sex

Frequency is higher in males; however, asymptomatic cases are more common in females.

Age

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FSHD is considered one of the more common hereditary muscular disorders with a prevalence of ~1 in 8,000. It appears to affect males and females in relatively equal numbers. The estimated prevalence is between four and ten per 100,000 people.[6, 7]

Physical

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Laboratory Studies

Serum creatine kinase levels are elevated.

Imaging Studies

Imaging studies show a selective destructive process involving the anterior compartment muscles of the leg. Hypertrophy of the psoas muscles also is observed occasionally.[9, 10]

Other Tests

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Procedures

Muscle biopsy: If results of genetic testing for FSHD are negative, a muscle biopsy is strongly recommended to rule out other conditions that mimic FSHD.

Histologic Findings

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Medical Care

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Surgical Care

Scapulothoracic arthrodesis may be attempted in select patients with preserved deltoid function. An improved functional range of abduction can be achieved if the scapula is fixed in 15-20° of rotation. In a series by Bunch and Siegel, 11 of 12 patients improved with this procedure.[14]

Demirhan, using multifilament cable for scapulothoracic arthrodesis, provided satisfactory function (Level IV evidence) in 13 patients.[15]

Medication Summary

The goals of pharmacotherapy are to reduce morbidity and prevent complications.

Albuterol (Ventolin, Proventil)

Clinical Context:  Relaxes bronchial smooth muscle by action on beta2-receptors with little effect on cardiac muscle contractility.

Class Summary

By activating cyclic AMP, this agent stimulates the ATPase pump, thereby activating the beta-adrenergic pathway. Albuterol reportedly improves muscle strength in FSHD patients through its nonspecific anabolic properties.

Complications

See the list below:

Prognosis

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What is facioscapulohumeral dystrophy (FSHD)?What is the pathophysiology of facioscapulohumeral dystrophy (FSHD)?What causes facioscapulohumeral dystrophy (FSHD)?What is the prevalence of facioscapulohumeral dystrophy (FSHD) in the US?What is the mortality associated with facioscapulohumeral dystrophy (FSHD)?What are the sexual predilections of facioscapulohumeral dystrophy (FSHD)?At what age does facioscapulohumeral dystrophy (FSHD) typically present?What is the prevalence of facioscapulohumeral dystrophy (FSHD)?What are the signs and symptoms of facioscapulohumeral dystrophy (FSHD)?What are the differential diagnoses for Facioscapulohumeral Dystrophy?What is the role of lab tests in the workup of facioscapulohumeral dystrophy (FSHD)?What is the role of imaging studies in the workup of facioscapulohumeral dystrophy (FSHD)?What is the role of EMG in the workup of facioscapulohumeral dystrophy (FSHD)?What is the role of biopsy in the workup of facioscapulohumeral dystrophy (FSHD)?Which histologic findings are characteristic of facioscapulohumeral dystrophy (FSHD)?How is facioscapulohumeral dystrophy (FSHD) treated?What is the role of surgery in the treatment of facioscapulohumeral dystrophy (FSHD)?What is the role of medications in the treatment of facioscapulohumeral dystrophy (FSHD)?Which medications in the drug class Beta2-adrenergic agonists are used in the treatment of Facioscapulohumeral Dystrophy?What are the possible complications of facioscapulohumeral dystrophy (FSHD)?What is the prognosis of facioscapulohumeral dystrophy (FSHD)?

Author

Naganand Sripathi, MD, Director, Neuromuscular Clinic, Department of Neurology, Henry Ford Hospital

Disclosure: Nothing to disclose.

Specialty Editors

Francisco Talavera, PharmD, PhD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Kenneth J Mack, MD, PhD, Senior Associate Consultant, Department of Child and Adolescent Neurology, Mayo Clinic

Disclosure: Nothing to disclose.

Chief Editor

Amy Kao, MD, Attending Neurologist, Children's National Medical Center

Disclosure: Have stock (managed by a financial services company) in healthcare companies including Allergan, Cellectar Biosciences, CVS Health, Danaher Corp, Johnson & Johnson.

Additional Contributors

James J Riviello, Jr, MD, George Peterkin Endowed Chair in Pediatrics, Professor of Pediatrics, Section of Neurology and Developmental Neuroscience, Professor of Neurology, Peter Kellaway Section of Neurophysiology, Baylor College of Medicine; Chief of Neurophysiology, Director of the Epilepsy and Neurophysiology Program, Texas Children's Hospital

Disclosure: Partner received royalty from Up To Date for section editor.

References

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