Shprintzen-Goldberg craniosynostosis syndrome

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Shprintzen-Goldberg craniosynostosis syndrome


Shprintzen-Goldberg craniosynostosis syndrome (SGS) is a disorder of the connective tissue, featuring craniosynostosis and marfanoid body type.


SGS, also known as marfanoid craniosynostosis syndrome, is one of a group of disorders characterized by craniosynostosis and marfanoid body type. It is a condition that involves craniofacial, skeletal, and other abnormalities. SGS is caused by genetic mutations (changes affecting the structure and function of the gene ) in a gene that contributes to the formation of connective tissue.

Genetic profile

SGS is associated with abnormalities of the elastic fibers of connective tissue. Elastic fibers are complex in structure and are composed of at least 19 different proteins. Mutations in three of the genes that encode the majority of these 19 proteins cause abnormalities in several body systems, including the skeletal system, blood vessels, and eye.

SGS shares characteristics with the Marfan syndrome , which is an inherited genetic disorder of the connective tissue which involves the eye, heart, aorta, and skeletal system. Marfan syndrome is caused by mutations in the fibrillin-1 (FBN1) gene, which is located on chromosome 15. Since SGS is similar in many ways to Marfan syndrome, studies of the FBN1 gene were conducted on SGS patients to see if they also had mutations in this gene. There were indeed abnormalities found in the FBN1 genes of persons with SGS. Researchers think that these mutations predispose a person to develop SGS, but that other factors are required in addition to the mutation in the gene to develop the disease. The other factors may be genetic mutations, environmental influences, or a combination of these, but they are not well-understood at this time.

The mutations appear to be sporadic in nature (not inherited), and are autosomal dominant (only one mutation is necessary to be predisposed to the disease). Sporadic genetic mutations in the sperm occur (in any gene, not just FBN1) at a higher rate in older men (over 45 years) and there is in fact one case report of a child with SGS in which the father was 49 years old. The father of another child with SGS reportedly had chemotherapy and radiation treatment prior to conception of the child. The recurrence risk for siblings is probably low, although such data is not available.


There are 15 reported cases as of 2000, with the first case being described in 1981. The ratio of females to males is 10:5, making females affected twice as often as males. Ethnicities would be expected to be affected equally with sporadic mutations, although data regarding SGS specifically is limited.

Signs and symptoms

Findings in SGS include skeletal abnormalities, hydrocephalus , and mental retardation. Most babies have been born well-nourished and had a relatively long birth length. The most frequently described craniofacial features of SGS include abnormal head shape (dolichocephaly), a high, prominent forehead, bulging eyes (ocular proptosis), wide spaced eyes (hypertelorism), downslanting eyes, strabismus (wandering eye), small jaw (maxillary hypoplasia), high narrow palate (roof of the mouth), and low-set ears.

The main skeletal findings in persons with SGS include long, thin fingers (arachnodactyly—or spider-like fingers), flat feet (pes planus), "bird" chest deformity (pectus deformity), scoliosis (curvature of the spine), and joint hypermobility (loose joints).

Other features can include clubfoot , enlarged aortic root, mitral valve prolapse (floppy heart valve which allows flow of blood back into the chamber of the heart that it came from), low muscle tone (hypotonia), developmental delay, mental retardation, very little body fat, and small penis in males. Myopia (near-sightedness) and abdominal wall defects (developmental problem that occurs during formation of the fetus where parts of the intestine or other organs can protrude outside of the body; usually surgically correctable) can also occur.

Radiologic findings include hydrocephalus (water on the brain), certain brain malformations (Chiari-I malformation or dilatation of the lateral ventricles), abnormalities in the first and second cervical vertebrae (vertebrae in the neck), square shaped vertebrae, thin ribs, thinning of the bones, and craniofacial abnormalities.


There are more than 75 syndromes associated with craniosynostosis. There are also a number of different syndromes associated with both craniosynostosis and marfanoid body type. X-ray evaluation can be helpful in determining whether a person has SGS, as they tend to have abnormal first and second cervical vertebrae, hydrocephalus (water on the brain), and certain brain malformations.

SGS must be differentiated from other syndromes with craniosynostosis and marfaniod body type. Two such syndromes include Idaho syndrome II and Antley-Bixler syndrome. Idaho syndrome II has less severe craniofacial problems than SGS and has abnormal leg bones and absent patellae (knee caps). Antley-Bixler syndrome is an inherited syndrome with craniofacial abnormalities, abnormal arm and leg bones, and fractures in the femurs (thigh bones). These characteristics are different from SGS. A clinical geneticist is a physician who has special training in recognizing and diagnosing rare genetic conditions and is a good resource for differentiating among these complicated and similar conditions.

Treatment and management

Cardiology evaluation is important since several children have been reported to have severe cardiac disease with SGS. Aortic root must be evaluated and measured routinely to minimize the risk for rupture. Enlarged aortic roots may need to be surgically repaired.

Patients should have an opthalmalogic evaluation, since mutations in the FBR1 gene are associated with abnormalities in the eyes.

Surgical correction of craniofacial problems or pectus are sometimes necessary or desirable. Shunting (surgical placement of a shunt to drain the accumulated fluid in the brain to the abdominal cavity to relieve pressure) may be required for patients with hydrocephalus. Orthopedic devices may be required for scoliosis or other bone abnormalities.

Special education for mentally retarded individuals or individuals with developmental delay is recommended.

Genetic counseling is recommended for persons with relatives diagnosed with SGS.


SGS does not alter lifespan, although complications from associated abnormalities such as mental retardation or respiratory problems can cause problems.



Gorlin, R.J., M.M. Cohen, and L.S. Levin. "Marfaniod Features and Craniosynostosis (including Shprintzen-Goldberg Syndrome)." In Syndromes of the Head and Neck. New York: Oxford University Press, 1990.


Furlong, J., T.W. Kurczynski, and J.R. Hennessy. "New Marfanoid Syndrome with Craniosynostosis." American Journal of Medical Genetics 26 (1987): 599-604.

Greally, M.T., et al. "Shprintzen-Goldberg Syndrome: A Clinical Analysis." American Journal of Medical Genetics 76 (1998): 202-212.

Lee, Y.C., et al. "Marfanoid Habitus, Dysmorphic Features, and Web Neck." Southerna Medical Journal 93 (2000): 1197-1200


Coalition for Heritable Disorders of Connective Tissue (CHDCT). 382 Main Street, Port Washington, NY 11050. (516) 883-8712. <>.

Hydrocephalus Association. 870 Market St. Suite 705, San Francisco, CA 94102. (415) 732-7040 or (888) 598-3789. Fax: (415) 732-7044. [email protected]. <>.


National Organization for Rare Diseases (NORD). <>.

"Shprintzen-Goldberg Craniosynostosis Syndrome." OnlineMendelian inheritance in Man (OMIM).<>.

Amy Vance, MS, CGC