Skip Navigation
Genetics Home Reference: your guide to understanding genetic conditions     A service of the U.S. National Library of Medicine®

Shprintzen-Goldberg syndrome

Reviewed February 2013

What is Shprintzen-Goldberg syndrome?

Shprintzen-Goldberg syndrome is a disorder that affects many parts of the body. Affected individuals have a combination of distinctive facial features and skeletal and neurological abnormalities.

A common feature in people with Shprintzen-Goldberg syndrome is craniosynostosis, which is the premature fusion of certain skull bones. This early fusion prevents the skull from growing normally. Affected individuals can also have distinctive facial features, including a long, narrow head; widely spaced eyes (hypertelorism); protruding eyes (exophthalmos); outside corners of the eyes that point downward (downslanting palpebral fissures); a high, narrow palate; a small lower jaw (micrognathia); and low-set ears that are rotated backward.

People with Shprintzen-Goldberg syndrome are often said to have a marfanoid habitus, because their bodies resemble those of people with a genetic condition called Marfan syndrome. For example, they may have long, slender fingers (arachnodactyly), unusually long limbs, a sunken chest (pectus excavatum) or protruding chest (pectus carinatum), and an abnormal side-to-side curvature of the spine (scoliosis). People with Shprintzen-Goldberg syndrome can have other skeletal abnormalities, such as one or more fingers that are permanently bent (camptodactyly) and an unusually large range of joint movement (hypermobility).

People with Shprintzen-Goldberg syndrome often have delayed development and mild to moderate intellectual disability.

Other common features of Shprintzen-Goldberg syndrome include heart or brain abnormalities, weak muscle tone (hypotonia) in infancy, and a soft out-pouching around the belly-button (umbilical hernia) or lower abdomen (inguinal hernia).

Shprintzen-Goldberg syndrome has signs and symptoms similar to those of Marfan syndrome and another genetic condition called Loeys-Dietz syndrome. However, intellectual disability is more likely to occur in Shprintzen-Goldberg syndrome than in the other two conditions. In addition, heart abnormalities are more common and usually more severe in Marfan syndrome and Loeys-Dietz syndrome.

How common is Shprintzen-Goldberg syndrome?

Shprintzen-Goldberg syndrome is a rare condition, although its prevalence is unknown. It is difficult to identify the number of affected individuals, because some cases diagnosed as Shprintzen-Goldberg syndrome may instead be Marfan syndrome or Loeys-Dietz syndrome, which have overlapping signs and symptoms.

What genes are related to Shprintzen-Goldberg syndrome?

Shprintzen-Goldberg syndrome is often caused by mutations in the SKI gene. This gene provides instructions for making a protein that regulates the transforming growth factor beta (TGF-β) signaling pathway. The TGF-β pathway regulates many processes, including cell growth and division (proliferation), the process by which cells mature to carry out special functions (differentiation), cell movement (motility), and the self-destruction of cells (apoptosis). By attaching to certain proteins in the pathway, the SKI protein blocks TGF-β signaling. The SKI protein is found in many cell types throughout the body and appears to play a role in the development of many tissues, including the skull, other bones, skin, and brain.

SKI gene mutations involved in Shprintzen-Goldberg syndrome alter the SKI protein. The altered protein is no longer able to attach to proteins in the TGF-β pathway and block signaling. As a result, the pathway is abnormally active. Excess TGF-β signaling changes the regulation of gene activity and likely disrupts development of many body systems, including the bones and brain, resulting in the wide range of signs and symptoms of Shprintzen-Goldberg syndrome.

Not all cases of Shprintzen-Goldberg syndrome are caused by mutations in the SKI gene. Other genes may be involved in this condition, and in some cases, the genetic cause is unknown.

Related Gene(s)

Changes in these genes are associated with Shprintzen-Goldberg syndrome.

  • FBN1
  • SKI

How do people inherit Shprintzen-Goldberg syndrome?

Shprintzen-Goldberg syndrome is described as autosomal dominant, which means one copy of the altered gene in each cell is sufficient to cause the disorder. The condition almost always results from new (de novo) gene mutations and occurs in people with no history of the disorder in their family. Very rarely, people with Shprintzen-Goldberg syndrome have inherited the altered gene from an unaffected parent who has a gene mutation only in their sperm or egg cells. When a mutation is present only in reproductive cells, it is known as germline mosaicism.

Where can I find information about diagnosis or management of Shprintzen-Goldberg syndrome?

These resources address the diagnosis or management of Shprintzen-Goldberg syndrome and may include treatment providers.

  • Gene Review: Shprintzen-Goldberg Syndrome (
  • Genetic Testing Registry: Shprintzen-Goldberg syndrome (
  • Johns Hopkins Medicine: Diagnosis of Craniosynostosis (
  • MedlinePlus Encyclopedia: Craniosynostosis (

You might also find information on the diagnosis or management of Shprintzen-Goldberg syndrome in Educational resources and Patient support.

General information about the diagnosis ( and management ( of genetic conditions is available in the Handbook. Read more about genetic testing (, particularly the difference between clinical tests and research tests (

To locate a healthcare provider, see How can I find a genetics professional in my area? ( in the Handbook.

Where can I find additional information about Shprintzen-Goldberg syndrome?

You may find the following resources about Shprintzen-Goldberg syndrome helpful. These materials are written for the general public.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

What other names do people use for Shprintzen-Goldberg syndrome?

  • Marfanoid-craniosynostosis syndrome
  • Shprintzen-Goldberg craniosynostosis syndrome

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines ( and How are genetic conditions and genes named? ( in the Handbook.

What if I still have specific questions about Shprintzen-Goldberg syndrome?

Ask the Genetic and Rare Diseases Information Center (

What glossary definitions help with understanding Shprintzen-Goldberg syndrome?

apoptosis ; arachnodactyly ; autosomal ; autosomal dominant ; camptodactyly ; cell ; craniosynostosis ; differentiation ; disability ; egg ; exophthalmos ; gene ; germline ; germline mosaicism ; growth factor ; hernia ; hypermobility ; hypertelorism ; hypotonia ; inguinal ; inherited ; joint ; lower jaw ; micrognathia ; mosaicism ; muscle tone ; mutation ; neurological ; palate ; pectus excavatum ; prevalence ; proliferation ; protein ; reproductive cells ; scoliosis ; sperm ; syndrome

You may find definitions for these and many other terms in the Genetics Home Reference Glossary.


  • Carmignac V, Thevenon J, Adès L, Callewaert B, Julia S, Thauvin-Robinet C, Gueneau L, Courcet JB, Lopez E, Holman K, Renard M, Plauchu H, Plessis G, De Backer J, Child A, Arno G, Duplomb L, Callier P, Aral B, Vabres P, Gigot N, Arbustini E, Grasso M, Robinson PN, Goizet C, Baumann C, Di Rocco M, Sanchez Del Pozo J, Huet F, Jondeau G, Collod-Beroud G, Beroud C, Amiel J, Cormier-Daire V, Rivière JB, Boileau C, De Paepe A, Faivre L. In-frame mutations in exon 1 of SKI cause dominant Shprintzen-Goldberg syndrome. Am J Hum Genet. 2012 Nov 2;91(5):950-7. doi: 10.1016/j.ajhg.2012.10.002. Epub 2012 Oct 25. (
  • Doyle AJ, Doyle JJ, Bessling SL, Maragh S, Lindsay ME, Schepers D, Gillis E, Mortier G, Homfray T, Sauls K, Norris RA, Huso ND, Leahy D, Mohr DW, Caulfield MJ, Scott AF, Destrée A, Hennekam RC, Arn PH, Curry CJ, Van Laer L, McCallion AS, Loeys BL, Dietz HC. Mutations in the TGF-β repressor SKI cause Shprintzen-Goldberg syndrome with aortic aneurysm. Nat Genet. 2012 Nov;44(11):1249-54. doi: 10.1038/ng.2421. Epub 2012 Sep 30. (
  • Gene Review: Shprintzen-Goldberg Syndrome (
  • Kosaki K, Takahashi D, Udaka T, Kosaki R, Matsumoto M, Ibe S, Isobe T, Tanaka Y, Takahashi T. Molecular pathology of Shprintzen-Goldberg syndrome. Am J Med Genet A. 2006 Jan 1;140(1):104-8; author reply 109-10. (
  • Robinson PN, Neumann LM, Demuth S, Enders H, Jung U, König R, Mitulla B, Müller D, Muschke P, Pfeiffer L, Prager B, Somer M, Tinschert S. Shprintzen-Goldberg syndrome: fourteen new patients and a clinical analysis. Am J Med Genet A. 2005 Jun 15;135(3):251-62. (
  • Shanske AL, Goodrich JT, Ala-Kokko L, Baker S, Frederick B, Levy B. Germline mosacism in Shprintzen-Goldberg syndrome. Am J Med Genet A. 2012 Jul;158A(7):1574-8. doi: 10.1002/ajmg.a.35388. Epub 2012 May 25. (
  • Sood S, Eldadah ZA, Krause WL, McIntosh I, Dietz HC. Mutation in fibrillin-1 and the Marfanoid-craniosynostosis (Shprintzen-Goldberg) syndrome. Nat Genet. 1996 Feb;12(2):209-11. (


The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? ( in the Handbook.

Reviewed: February 2013
Published: February 1, 2016