POMGNT1-related disorders, a group of muscular dystrophy-dystroglycanopathies (MDDG) vary in severity and impact several different parts of the body.
Muscular Dystrophy-Dystroglycanopathy Type A3 (MDDGA3): This includes Walker-Warburg syndrome (WWS) and muscle-eye-brain disease (MEB). It causes significant muscle weakness, vision problems, brain changes, and severe intellectual disabilities. Children may feel floppy in infancy and struggle with motor skills in childhood. Eye issues like near-sightedness and glaucoma are common. Brain abnormalities include fluid buildup and underdeveloped brainstem. Seizures and intellectual disability are expected, with varying severity. Most individuals have severe effects, leading to shortened lifespans.
Muscular Dystrophy-Dystroglycanopathy Type B3 (MDDGB3): Also known as Fukuyama congenital muscular dystrophy (FCMD), it causes significant and progressive muscle weakness, generally less severe than MDDGA3. Some children may eventually walk. Eye problems are variable but milder than MDDGA3. Developmental delays, moderate intellectual disability, seizures, and brain changes are common.
Muscular Dystrophy-Dystroglycanopathy Type C3 (MDDGC3): Referred to as limb-girdle muscular dystrophy (LGMD) type 20, it is the mildest of POMGNT1-related disorders. Symptoms include weakness in muscles close to the body’s center, affecting shoulders, upper arms, pelvic area, and thighs. The weakness is progressive but may vary. The brain and eyes are not affected, and intelligence and lifespan are typically normal.
There is no cure for these disorders. Treatments focus on symptom management, including physical and occupational therapy, vision services, glasses, and medication for seizures.
This group of conditions is caused by pathogenic (disease-causing) variants in the POMGNT1 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.