FKTN-related disorders encompass a spectrum of conditions causing muscle weakness due to a deficiency in the fukutin protein.

The severity of symptoms varies widely, even within the same family. The disorders range from the most severe, Walker-Warburg Syndrome (WWS), characterized by significant muscle weakness, vision problems, brain structural changes, and severe intellectual disabilities. Impaired vision can result from various eye issues, and brain changes often lead to abnormal folding or fluid buildup. Children with WWS are typically unable to sit or walk independently and often experience seizures.

Fukuyama Congenital Muscular Dystrophy (FCMD) and Muscle-Eye-Brain Disease (MEB) share overlapping symptoms with WWS but tend to be less severe. Muscle weakness, brain structural alterations, and eye abnormalities are present, although some individuals with FCMD or MEB may learn to walk and speak a few words at later stages.

Limb Girdle Muscular Dystrophy Type 2M (LGMD2M) represents the mildest form of FKTN-related disorders, characterized by weakness in muscles near the body’s center, particularly in shoulders, upper arms, pelvic area, and thighs. Heart conditions like dilated cardiomyopathy are rare in this presentation, and the brain and eyes remain unaffected. Currently, there is no cure for these disorders. Treatment focuses on managing symptoms, which may involve seizure medications, brain fluid reduction surgery, feeding tube placement, and physical and occupational therapy for more severe cases. Management for LGMD2M mainly includes physical therapy, assistive devices, and monitoring for heart and breathing complications.

These conditions are caused by pathogenic (disease-causing) variants in the FKTN gene and exhibits autosomal recessive inheritance. This means that both parents must be carriers to have a 25% chance to have a child with the condition. The risk of being a carrier is based on a person’s ancestry or ethnic background. For example, individuals of Ashkenazi Jewish descent have a 1 in 80 chance to be a carrier. Carriers typically do not experience any symptoms. 

Other names for this condition include Walker-Warburg syndrome, limb girdle muscular dystrophy type 2M, Fukuyama congenital muscular dystrophy/muscle-eye-brain disease, and FKTN-related dystrophies. 

Resources:  

Limb Girdle Awareness Foundation

National Organization for Rare Disorders (NORD)

Revised October 2023