Shprintzen-Goldberg syndrome

SGS is a very rare disease; its prevalence is unknown.

Shprintzen-Goldberg syndrome is inherited in an autosomal dominant manner.

Shprintzen-Goldberg syndrome is diagnosed primarily by molecular genetic testing; no consensus clinical criteria have been established. The clinical suspicion is raised by the characteristic combination of craniosynostosis, marfanoid skeletal habitus, mild-to-moderate intellectual disability, and cardiovascular involvement and is confirmed by detection of a heterozygous germline pathogenic variant in SKI.

Main differential diagnoses include:

• : tall stature and ectopia lentis are most commonly present; craniosynostosis and developmental delay are absent
• : widespread arterial tortuosity, aneurysms outside the aortic root, and early arterial dissection; developmental delay typically absent
• : dolichostenomelia and arachnodactyly with characteristic ‘crumpled’ upper helix of the external ear; craniosynostosis and intellectual disability absent

• Establishing the diagnosis: molecular genetic testing confirms the clinical suspicion and provides the basis for accurate diagnosis and genetic counselling of the affected individual and their family.
• Clinical management: identification of the underlying pathogenic variant can inform clinical follow-up and support management of cardiovascular, skeletal, and neurodevelopmental complications.
• Family member testing: once the familial pathogenic variant has been identified, predictive testing of at-risk relatives can clarify their genetic status and inform clinical follow-up and genetic counselling.

• Greally MT. Shprintzen-Goldberg syndrome. 2006 Jan 13 [updated 2020 Apr 9]. In: Adam MP, Bick S, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews^® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2026. PMID: .
• Gori I, George R, Purkiss AG, Strohbuecker S, Randall RA, Ogrodowicz R, et al. Mutations in SKI in Shprintzen-Goldberg syndrome lead to attenuated TGF-β responses through SKI stabilization. eLife. 2021;10. PMID: .
• Fusco C, Nardella G, Morlino S, Micale L, Tragni V, Agolini E, et al. Nucleotide substitutions at the p.Gly117 and p.Thr180 mutational hot-spots of SKI alter molecular dynamics and may affect cell cycle. J Hum Genet. 2024;69(1):53-58. PMID: .