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.
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
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:
- Facial abnormalities such as an elongated head, a high forehead and eyes that protrude and are widely spaced
- Brain abnormalities such as hydrocephalus and the enlargement of the lateral ventricles
- An abnormally high, narrow palate and an under-developed jaw
- Cardiac abnormalities including mitral valve regurgitation and aortic valve regurgitation, and mitral valve prolapse
- Arachnodactyly – long and thin fingers.
- Flaccid musculature, particularly in infancy
- Contractures (shortening) of some joints and joint hypermobility
- Umbilical hernias and inguinal hernias
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.
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:
- Hydrocephalus may be managed by surgically placing shunts that will drain excess fluid in the brain into the abdominal cavity, which can reduce pressure within the brain cavity (intracranial pressure). The fluid that will drain is cerebrospinal fluid. Occupational therapy may be required to address any cognitive impairment or disability that results.
- Craniofacial deformities may need to be corrected surgically. In many cases, this will require the efforts of a multidisciplinary team that could include neurosurgeons, orthodontists, otolaryngologists and plastic surgeons.
- Scoliosis may need to be managed with orthopedic devices such as back braces or in severe cases, with spinal surgeries such as vertebral fusions and bone grafts.
- Cardiovascular symptoms. Mitral and aortic valve abnormalities may require medications as well as surgical repairs or replacements of the affected valves (mitral valve replacements and aortic valve replacements).
- Joint contractures may need to be treated with physical therapy which could include passive and active range of motion exercises as well as with braces (orthotics) and other compensatory strategies designed to keep contractures from worsening.
- Umbilical and inguinal hernias. Depending upon the severity of symptoms and the potential for the development of secondary conditions like strangulated bowels, abdominal hernias may need to be surgically repaired or reduced. Hernia repair may involve open surgery or laparoscopic surgery.
Prevention & Prophylaxis