SHPRINTZEN-GOLDBERG SYNDROME (SGS)

Shprintzen-Goldberg syndrome (SGS) is characterized by craniofacial anomalies, skeletal abnormalities, CNS abnormalities and learning disabilities, although cardiovascular disease such as mitral valve prolapse and aortic regurgitation may also occur. It shows phenotypic similarities with Marfan syndrome and Loeys-Dietz syndrome, but has additional symptoms such as mental retardation and hypotonia of the skeletal muscles. It is caused by pathogenic variants in the SKI gene, which codes for the proto-oncoprotein SKI.

Also called

• Marfanoid-craniosynostosis syndrome
• Shprintzen-Goldberg craniosynostosis syndrome
• Craniosynostosis with arachnodactyly and abdominal hernias
• Marfanoid disorder with craniosynostosis type 1
• Shprintzen-Goldberg marfanoid syndrome

Symptoms

Characteristic clinical symptoms of Shprintzen-Goldberg syndrome are:

• Craniofacial anomalies (craniosynostosis, characteristic facial dysmorphism)
• Skeletal anomalies (dolichostenomelia, arachnodactyly, camptodactyly, pes planus, pectus excavatum or carinatum, scoliosis, hypermobile joints or contractures and C1/C2 malformations of the spine)
• CNS abnormalities (hydrocephalus, dilatation of the lateral ventricles, Chiari 1 malformation)
• Learning disability

Cardiovascular involvement may include mitral valve prolapse, mitral valve regurgitation, aortic regurgitation and aortic root dilatation.

Causes

SGS is caused by heterozygous, pathogenic variants in the SKI gene, which codes for the SKI proto-oncoprotein. The SKI proto-oncoprotein family proteins are negative regulators of SMAD-dependent TGF-β signaling. All pathogenic variants described so far in the SKI gene affect exon 1 and are localized within two N-terminal regions of the protein. To date, only one genomic deletion has been described in the form of a 576 kb microdeletion in the 1p36.33-p36.32 region, which includes the SKI gene and leads to a clinical phenotype with rib malformation, heart defects, epilepsy and developmental delay.

Differential Diagnosis

Syndromes with similar symptoms include Marfan syndrome, Loeys-Dietz syndrome and congenital contractural arachnodactyly.