Shprintzen-Goldberg syndrome

Medical quality assurance by Dr. Albrecht Nonnenmacher, MD at July 27, 2016
StartDiseasesShprintzen-Goldberg syndrome

Shprintzen-Goldberg syndrome (SGS) is a rare genetic condition that was first identified in 1982. The condition is believed to be most often caused by a spontaneous mutation of the SKI gene, which regulates the formation of connective tissue. It’s sometimes called Marfanoid-craniosynostosis syndrome because it shares several key skeletal abnormalities in common with Marfan syndrome.

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Definition & Facts

Shprintzen-Goldberg Syndrome is a genetic disorder that is characterized by profound craniofacial, neurological, skeletal, cardiovascular and connective tissue abnormalities. Individuals with Shprintzen-Goldberg syndrome are typically affected by craniosynostosis, facial abnormalities, abnormalities of the skeletal system and central nervous system, and developmental delays.

However, while SGS is frequently associated with mild to moderate neurologic abnormalities, including hydrocephalus, Marfan syndrome is not. Additionally, whereas Marfan syndrome occurs in as many as one out of every 5,000 individuals, SGS is extremely rare.

Shprintzen-Goldberg syndrome was first recognized as a distinct clinical entity by R.J. Shprintzen and R. Goldberg who published the results of their investigations in an article that appeared in 1982 in “The Journal of Craniofacial Genetics and Developmental Biology.” The article was entitled “A recurrent pattern syndrome of craniosynostosis associated with arachnodactyly and abdominal hernias."

Symptoms & Complaints

Shprintzen-Goldberg syndrome is characterized by a set of distinctive signs and symptoms that show some variation from affected individual to affected individual. The most common of these symptoms is craniostenosis.

At birth, a normal infant’s skull is comprised of seven bones separated by sutures that do not fuse until the child is approximately 24 months old; this gives the infant's brain the opportunity to grow.

In individuals with SGS, however, cranial sutures fuse prematurely, which can lead to problems with brain growth and intellectual disability. Other physical signs and symptoms associated with Shprintzen-Goldberg syndrome include:

Causes

Scientists believe that Shprintzen-Goldberg syndrome is linked to mutations of the SKI gene, a chromosomal locus that encodes a protein that regulates the TGF-β (transforming growth factor beta) signaling pathway. SKI mutations affect SKI proteins so that SKI proteins are no longer able to attach to TGF-β proteins. This promotes abnormally high levels of TGF-β signaling, which leads to the disruption of normal development within many different systems throughout the body but most noticeably affects the bones and the brain.

In rare instances, SGS may also be associated with malformations in the FBN1 gene. FBN1 genetic mutations are also linked to Marfan syndrome.

Family history does not play a role in having this condition; that is Shrprintzen-Goldberg syndrome arises from a de novo mutation in which the mutation occurs for the first time. Shrprintzen-Goldberg syndrome can also be idiopathic, meaning that the cause is unknown.

Diagnosis & Tests

Diagnosis of Shprintzen-Goldberg syndrome follows a thorough physical examination that confirms the specific craniofacial, neurological, skeletal and cardiovascular abnormalities that are associated with this condition. As noted, the disorder is extremely rare, and it also presents variably with degrees of severity that differ from affected individual to affected individual, so SGS is usually diagnosed only after other conditions have been ruled out.

The diagnosis is frequently made in infancy and involves X-rays, computed tomography (CT) scans and other imaging studies to confirm the degree of craniosynostosis that’s involved. Genetic testing can also identify those mutations in the SKI gene that are most frequently associated with Shprintzen-Goldberg syndrome. It’s important to remember, though, that SGS is not always associated with mutations of the SKI gene.

Treatment & Therapy

Once a diagnosis of Shprintzen-Goldberg syndrome is confirmed, the affected individual will be monitored medically with frequent imaging studies and echocardiograms. SGS is not associated with a shortened lifespan, so affected individuals will require ongoing support throughout their lives and may need repeated medical and surgical interventions over many years.

Therapy will be managed on a system-by-system basis depending upon the severity and presentation of each individual set of symptoms. These symptoms and their respective treatments can include:

Prevention & Prophylaxis

Since Shprintzen-Goldberg syndrome, in most instances, is believed to arise as the result of a spontaneous mutation rather than as an inherited condition, prevention as such is not a realistic goal.