Marinesco-Sjögren syndrome

Marinesco-Sjögren syndrome (MSS) is a rare autosomal recessive multisystem disorder characterized by the classic triad of cerebellar ataxia, congenital cataracts, and intellectual disability. The condition was first described independently by Marinesco and Sjögren in the early-to-mid 20th century. MSS is caused in most cases by biallelic mutations in the SIL1 gene (also known as BAP), which encodes a co-chaperone involved in protein folding in the endoplasmic reticulum. Loss of SIL1 function leads to endoplasmic reticulum stress and impaired protein quality control, particularly affecting the cerebellum, lens, skeletal muscle, and developing brain. The neurological features include progressive cerebellar ataxia due to cerebellar atrophy, with onset typically in infancy or early childhood. Bilateral cataracts are usually present at birth or develop in early infancy and often require surgical removal. Intellectual disability ranges from mild to severe. Additional features commonly include progressive myopathy with elevated creatine kinase levels, short stature, skeletal abnormalities (such as scoliosis and pes planus), hypergonadotropic hypogonadism, and delayed motor milestones. Muscle biopsy may show characteristic rimmed vacuoles and autophagic changes. There is currently no cure or disease-modifying treatment for Marinesco-Sjögren syndrome. Management is supportive and multidisciplinary, including early cataract surgery to optimize vision, physical and occupational therapy for motor difficulties, speech therapy, educational support for intellectual disability, and orthopedic management for skeletal complications. Regular monitoring by neurology, ophthalmology, endocrinology, and rehabilitation specialists is recommended. Prognosis varies, but many individuals survive into adulthood with appropriate supportive care, though progressive cerebellar and muscular involvement may lead to significant disability over time.

Common questions about Marinesco-Sjögren syndrome