Qualitative or quantitative defects of protein O-mannosyltransferase 2

Qualitative or quantitative defects of protein O-mannosyltransferase 2 (POMT2) refer to a group of rare congenital muscular dystrophy-dystroglycanopathy syndromes caused by mutations in the POMT2 gene. POMT2 encodes an enzyme essential for the O-mannosylation of alpha-dystroglycan, a key glycoprotein that links the intracellular cytoskeleton to the extracellular matrix in skeletal muscle, brain, and eye tissues. When POMT2 is deficient or dysfunctional, alpha-dystroglycan is hypoglycosylated, leading to impaired cellular adhesion and structural integrity in multiple organ systems. The clinical spectrum associated with POMT2 defects ranges from severe to milder phenotypes. The most severe form is Walker-Warburg syndrome (muscular dystrophy-dystroglycanopathy type A2), characterized by severe congenital muscular dystrophy, cobblestone lissencephaly and other structural brain malformations, hydrocephalus, profound intellectual disability, and eye abnormalities including microphthalmia and retinal detachment. Affected infants typically present at birth with severe hypotonia and rarely survive beyond early childhood. Intermediate forms (type B2) present with congenital muscular dystrophy, variable intellectual disability, and structural brain changes but without the full severity of Walker-Warburg syndrome. Milder limb-girdle muscular dystrophy (type C2) may present later in childhood or adolescence with progressive proximal muscle weakness and variable cognitive involvement. There is currently no cure or disease-specific treatment for POMT2-related dystroglycanopathies. Management is supportive and multidisciplinary, involving neurologists, ophthalmologists, orthopedic specialists, and rehabilitation therapists. Interventions focus on seizure management, nutritional support, respiratory care, physical therapy, and surgical correction of orthopedic or ophthalmologic complications as needed. Genetic counseling is recommended for affected families.

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