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Hereditary Myopathy with Early Respiratory Failure.

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GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2017.
2014 Feb 27.

Author information

1
Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom
2
Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom

Excerpt

CLINICAL CHARACTERISTICS:

Hereditary myopathy with early respiratory failure (HMERF) is a slowly progressive myopathy that typically begins in the third to fifth decades of life. The usual presenting findings are gait disturbance relating to distal leg weakness or nocturnal respiratory symptoms due to respiratory muscle weakness. Weakness eventually generalizes and affects both proximal and distal muscles. Most affected individuals require walking aids within a few years of onset; some progress to wheelchair dependence and require nocturnal noninvasive ventilatory support. The disease course varies even among individuals within the same family: some remain ambulant until their 70s whereas others may require ventilator support in their 40s.

DIAGNOSIS/TESTING:

The diagnosis of HMERF is suspected based on clinical findings, usually mildly elevated serum creatine kinase (CK), and a typical (but not specific) pattern of fatty infiltration of the semitendinosus muscle and anterior compartment muscles of the lower leg noted on MRI. The diagnosis is established by the presence of a pathogenic variant in the region of TTN that encodes the 119th fibronectin-3 domain of titin.

MANAGEMENT:

Treatment of manifestations: Management is supportive. For distal leg weakness, use of ankle-foot orthoses can optimize independent ambulation early in the disease course; later in the disease course other mobility aids (canes, walkers, or wheelchairs) may be required. Noninvasive ventilation with bilevel positive airway pressure (BiPAP) or continuous positive airway pressure (CPAP) may be indicated for nocturnal hypoventilation initially, followed by mechanical ventilatory support as needed. Occupational therapy and social service support are important. Surveillance: Pulmonary function testing at intervals of six to 12 months, or guided by patient findings; reassessment of muscle strength and clinical status annually by a neurologist. Pregnancy management: Although the onset of symptoms usually occurs after the age of childbearing, a pregnant woman with early manifestations of HMERF or at risk for HMERF should be considered high risk because of the associated respiratory muscle weakness and the increased physiologic demands of pregnancy. Consultation with a high-risk maternal-fetal medicine specialist is recommended when possible.

GENETIC COUNSELING:

HMERF is inherited in an autosomal dominant manner. Most individuals diagnosed with HMERF have an affected parent; however, the proportion of cases caused by a de novo pathogenic variant is unknown. Each child of an individual with HMERF has a 50% chance of inheriting the pathogenic variant. If the pathogenic variant has been identified in an affected family member, prenatal testing for pregnancies at increased risk is possible.

Copyright © 1993-2017, University of Washington, Seattle. GeneReviews is a registered trademark of the University of Washington, Seattle. All rights reserved.

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