What is the relationship between Four-and-a-half LIM domains 1 (FHL1) and muscular dystrophy?

From the Guidelines

FHL1 gene mutations are a significant cause of muscular dystrophy, particularly X-linked myopathy with postural muscle atrophy (XMPMA), reducing body myopathy, and scapuloperoneal myopathy, characterized by progressive muscle weakness and cardiac involvement 1. When considering the management of patients with FHL1-related muscular dystrophies, it is crucial to prioritize a multidisciplinary approach to address the progressive nature of the disease and its impact on quality of life.

• Key aspects of management include:
  • Physical therapy to maintain muscle strength and range of motion
  • Occupational therapy to adapt to functional limitations
  • Respiratory support when breathing muscles are affected
  • Regular cardiac monitoring due to the high risk of cardiac involvement
• Genetic counseling is also essential for affected individuals and their families to understand the inheritance patterns of FHL1 mutations, which are located on the X chromosome, leading to more severe effects in males while females may be carriers or exhibit milder symptoms 1. The role of the FHL1 protein in muscle development and function underscores the importance of early diagnosis and intervention to potentially slow the progression of muscle degeneration and weakness associated with these muscular dystrophies.
• Recent studies, such as the one published in Circulation in 2017 1, highlight the expanding list of genes linked to myofibrillar myopathy, including FHL1, and emphasize the need for comprehensive care to address the multifaceted nature of these conditions.

From the Research

FHL1 and Muscular Dystrophy

• FHL1 mutations have been associated with various muscular dystrophies, including Emery-Dreifuss muscular dystrophy (EDMD) 2, reducing body myopathy (RBM) 3, and X-linked myopathy with postural muscle atrophy (XMPMA) 4, 5.
• The clinical features of FHL1-related muscular dystrophies include scapuloperoneal muscle weakness, rigid spine, cardiac involvement, and cytoplasmic bodies in muscle biopsies 3, 4, 5.
• FHL1 mutations can cause a range of phenotypes, from severe and fatal to mild and late-onset 6, 5.
• The FHL1 gene is located on the X chromosome, and mutations can be inherited in an X-linked recessive or dominant pattern 2, 4.

Emery-Dreifuss Muscular Dystrophy

• FHL1 mutations have been identified as a cause of X-linked recessive Emery-Dreifuss muscular dystrophy (EDMD) 2, 6.
• The clinical features of FHL1-related EDMD include early-onset joint contractures, progressive muscle weakness, and cardiac involvement 2, 6.
• FHL1 mutations can cause a mild phenotype of EDMD, with late-onset muscle symptoms and prominent cardiac involvement 6.

Reducing Body Myopathy

• FHL1 mutations have been associated with reducing body myopathy (RBM), a rare muscular dystrophy characterized by the presence of reducing bodies in muscle biopsies 3, 4.
• The clinical features of FHL1-related RBM include scapuloperoneal muscle weakness, rigid spine, and cardiac involvement 3, 4.
• FHL1 mutations can cause a range of phenotypes in RBM, from severe and fatal to mild and late-onset 3, 4.

Diagnosis and Screening

• Screening for FHL1 mutations should be considered in patients with muscular dystrophy and possible X-linked inheritance, particularly those with scapuloperoneal muscle weakness, rigid spine, and cardiac involvement 5.
• Muscle biopsies can be used to diagnose FHL1-related muscular dystrophies, with characteristic features including cytoplasmic bodies and reducing bodies 3, 4.