Shprintzen-Goldberg syndrome is often caused by defects (mutations) in the SKI gene. This gene provides instructions for making a protein that cause too much TGFbeta activity, which alters its function in tissue development and maintenance. The TGF-β signaling 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)
  • The self-destruction of cells (apoptosis)
​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. In Shprintzen-Goldberg syndrome, the SKI gene mutation prevents the TGF-β signaling pathway from carrying out its many functions in these areas.

Facial features of Shprintzen-Goldberg syndrome include:
  • A long, narrow head (dolichochephaly)
  • High prominent forehead
  • Widely spaced eyes (hypertelorism)
  • Protruding or bulging eyes (exophthalmos, ocular proptosis)
  • Wandering eye (strabismus) 
  • Outside corners of the eyes point downward (down-slanting palpebral fissures)
  • A high, narrow palate (roof of the mouth)
  • Under-developed jaw bones (maxillary hypoplasia)
  • Small lower jaw (micrognathia)
  • Low-set ears that are rotated backward
  • Increased angle of the eyelids (telecanthus)
  • Craniosynostosis ( early fusion of skull bones )
  • Hypertelorism
  • Molar Hypoplasia ( flat cheek bones )
  • Broad or Split Uvula
  • Cleft palate
  • Proptosis
  • Adnormal head shape
  • Blue sclerae ( blue tinge of the white of the eyes )

Skeletal Features:
  • C1/2 Spine malformation/ Instability
  • Usually large range of joint movement ( Joint Hypermobility )
  • Flat feet ( Pes Planus )
  • Petcus deformity ( Petcus carinatum outward chest or Petcus excavatum sunken in chest )
  • Scoliosis 
  • Kyphosis
  • Lordosis
  • Spondylolisthesis/ Anterolistheses
  • Dural Ectasia
  • Arachnodactyly
  • Camptodactyly
  • Hammer Toes
  • Club foot
  • Joint Contractures
  • Marfanoid Habitus: long arms and legs for the size of the trunk; low body weight
  • Winged Scapula 
  • Osteoprosis or Osteopenia :mild or severe problem with bone density)
  • Joint dislocations
  • Valgus foot deformities 
  • Joint inflamation
  • Osteoarthritis (Joint Inflammation)

​​​​​Features related to the heart and blood vessels include:
  • Valve prolapse
  • Valve regurgitation
  • Aortic root enlargement/ Aneurysm ​
Brain abnormalities include:
  • Brain anomalies, including hydrocephalus (water on the brain) 
  • Dilatation (enlargement) of the lateral ventricles
  • Chiari 1 malformation (brain tissue protrudes into the spinal canal)
  • Mild to moderate intelectual disability
Other characteristics include:
  • Soft or velvety skin 
  • Translucent skin ( your able to see lots of veins ) 
  • Weak muscle tone (hypotonia) 
  • A soft out-pouching around the belly-button ( Hernias)
  • ​Adnormal or wide scarring 
  • Developmental Delay 
  • Gastrointestinal Issues
  • Constipation
  • Low body fat
  • Easy brusing

​How is Shprintzen-Goldberg syndrome managed?

Management of Shprintzen-Goldberg syndrome depends on the extent of the features. To evaluate severity, the following tests are recommended:
  • ​ Skeletal survey, including skull series
  •  Brain MRI
  •  Echocardiogram by a cardiologist 
  •  CT/MRI of the vascular system
  • Surgical evaluation for hernia repair, if a hernia is suspected
  • Eye evaluation by an ophthalmologist
  • Cervical spine flexion and extentsion x-ray
  • Pulmonary function test
  • Sleep Apnea test
  • GERDS testing if acid reflux is suspected

Treatments may include:
  • Surgical repair of aneurysms/disections
  • Surgical repair/replacement of heart valves
  • Surgical correction of craniofacial or chest problems 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 (water on the brain)
  • Occupational Therapy
  • Physical Therapy
  • Bracing for feet and spine
  • Glasses 
  • Jaw surgery
  • Braces on the teeth
  • Surgical fusion of C1 and C2
  • Medications
  • Pediasure/ Insure for weight gain
  • Feeding tube
    Surgical intervention for constipation
    (Chait Trapdoor Cecostomy)​

    It is now recommended that Shprintzen-Goldberg patients have an ​​​computed tomography angiography (CTA) or a magnetic resonance anigograhpy (MRA) from the head to pelvic every 2 years.​ 

    ​Echocardiograms should be performed annually.

    Patients who have any aortic growth should be put on beta-blockers Atenolol or Losartan  angiotensin receptor blocker.​​

    X-Ray of neck and spine should be done annually as changes can occur quickly.​​

    Eye exams should be done by a opthamologist ​​who specializes in connective tissue disease annually.

    Anyone who has been diagnosed with Shprintzen-Goldberg Syndrome should have a Bone Density Scan performed. ​​