Facioscapulohumeral Dystrophy

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Background

Facioscapulohumeral dystrophy (FSHD) is one of the most common types of muscular dystrophy. 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.

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

Frequency

United States

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

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

Physical

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.

Other Tests

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

Medical Care

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.[7]

Demirhan, using multifilament cable for scapulothoracic arthrodesis, provided satisfactory function (Level IV evidence) in 13 patients.[8]

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

Prognosis

Author

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

Disclosure: Nothing to disclose.

Specialty Editors

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: Up To Date Royalty Section Editor

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

Disclosure: Medscape Salary Employment

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: Nothing to disclose.

References

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