Shprintzen-Goldberg syndrome

Shprintzen-Goldberg syndrome (SGS), also known as Shprintzen-Goldberg craniosynostosis syndrome, is an extremely rare connective tissue disorder characterized by craniosynostosis (premature fusion of skull bones), distinctive craniofacial features, skeletal abnormalities, and variable degrees of intellectual disability. The condition shares significant clinical overlap with Marfan syndrome and Loeys-Dietz syndrome but is distinguished by the presence of craniosynostosis and more prominent neurodevelopmental involvement. SGS is caused by pathogenic variants in the SKI gene (located on chromosome 1p36.33), which encodes a protein involved in TGF-beta signaling regulation. The syndrome affects multiple body systems. Craniofacial features include dolichocephaly, hypertelorism, downslanting palpebral fissures, maxillary and mandibular hypoplasia, and a high arched palate. Skeletal manifestations resemble those of Marfan syndrome and include arachnodactyly, camptodactyly, pectus deformity (excavatum or carinatum), scoliosis, joint hypermobility, and tall stature with marfanoid habitus. Cardiovascular involvement may include mitral valve prolapse, aortic root dilation, and other cardiac anomalies, though aortic dissection appears to be less common than in Loeys-Dietz syndrome. Neurological features include intellectual disability of variable severity, hypotonia, and brain anomalies such as hydrocephalus or Chiari malformation in some cases. Abdominal wall defects, including hernias, may also occur. There is currently no cure for Shprintzen-Goldberg syndrome, and management is supportive and multidisciplinary. Treatment involves surgical correction of craniosynostosis when indicated, orthopedic management of skeletal deformities, cardiac surveillance with echocardiography to monitor for aortic root dilation and valvular abnormalities, and developmental support including speech therapy, physical therapy, and educational interventions. Regular monitoring by a team including geneticists, cardiologists, orthopedic surgeons, and neurodevelopmental specialists is recommended. Beta-blockers or angiotensin receptor blockers may be considered for aortic root dilation, following protocols similar to those used in Marfan syndrome.

Common questions about Shprintzen-Goldberg syndrome