FKTN-related dystrophies include three overlapping diseases that make up a continuum of severity, known as limb-girdle muscular dystrophy type 2M, Fukuyama congenital muscular dystrophy, and Walker-Warburg syndrome. All three diseases are inherited in an autosomal recessive manner and are caused by pathogenic variants in the gene FKTN. Limb-girdle muscular dystrophy type 2M is characterized by onset of muscle weakness in the limbs in infancy, which is slowly progressive. Patients will learn to walk, but will eventually lose the ability. Intellect is not affected. Fukuyama congenital muscular dystrophy is a more severe disorder characterized by brain malformations, hypotonia and muscle weakness. Affected infants may have joint contractures, developmental delay and intellectual disability, and seizures. Death often occurs in late childhood or early adolescence due to difficulty swallowing and cardiomyopathy. WalkerWarburg syndrome is characterized by severe brain malformations, muscle weakness, hypotonia, feeding difficulties, seizures, blindness, and male genital anomalies. Onset of WalkerWarburg syndrome is at birth, and patients have a life expectancy of less than 3 years. Many variants are associated with a particular FKTN-related dystrophy, although the severity of disease may not be able to be predicted based on genotype in all patients.
For information about carrier frequency and residual risk, please see the residual risk table.