NORD gratefully acknowledges Dr. Albert Schinzel, Professor Emeritus, Institute of Medical Genetics, Schlieren, Switzerland, for assistance in the preparation of this report.
Schinzel Giedion syndrome (SGS) is a very rare genetic disorder with characteristic facial features, skeletal abnormalities, and obstruction of the tube that carries urine from the kidney to the bladder (ureter). This obstruction may lead to enlarged and damaged kidneys (hydronephrosis). Symptoms characteristic of SGS also include excessive hair-growth (hypertrichosis), a flat midface (midface retraction), seizures, clubfeet, broad ribs, profound intellectual disability and short arms and legs. SGS is caused by a new mutation in the SETBP1 gene that is not inherited from the parents. SGS is a severe progressive syndrome and most affected individuals do not survive infancy.
Schinzel Giedion syndrome is characterized by an unusual facial appearance as well as abnormalities of the skeleton, kidney, hair and brain. Individuals with this disorder have an obstruction of the tube that carries urine from the kidney into the bladder (ureter). This causes the kidney to become swollen as urine accumulates (hydronephrosis).
Failure to grow and develop normally becomes apparent at an early age. Excessive growth of hair as well as widely spaced eyes, a flat midface, low-set ears, a short low-set nose, and a short and wide neck with an excess of skin are typical features of individuals with Schinzel Giedion syndrome.
Abnormalities of the skeleton include widely spaced openings between the bones of the skull (patent fontanelles), and short lower arms and legs. Other skeletal signs may include clubfoot and broad ribs. Typical and specific findings on X-ray are a dense pyramid bone and gap between the two segments of the occipital bone.
Sudden, aimless, uncontrollable discharge of electrical energy in the brain causing convulsions and/or loss of consciousness (epileptic seizures) has been found in most patients with this disorder.
Visual and hearing problems as well as intellectual disability are also found in patients with Schinzel Giedion syndrome. A sleep disorder in which there is cessation of breathing during sleep (sleep apnea) may also be present.
Other symptoms found in some patients with Schinzel Giedion syndrome may include a high forehead that protrudes outward, a large tongue (macroglossia), delayed eruption of teeth, a narrow passage between the nose and throat (choanal stenosis), underdeveloped nipples, abnormal nails of the fingers and toes, extra fingers and/or toes, a clubfoot, a short penis, failure of the testicles to descent into the scrotum (cryptorchidism), and/or a deep depression in the fold of skin at the opening of the vagina (interlabial sulcus).
A common form of heart disease characterized by an abnormal opening between the two atria chambers of the heart (atrial septal defect) has also been found in the majority of reported cases of Schinzel Giedion syndrome.
The main complications of Schinzel Giedion syndrome are feeding difficulties, respiratory failure, recurrent infections (e.g. pneumonia) and refractory seizures.
Schinzel Giedion syndrome is caused by a new spontaneous mutation of the SETBP1 gene. The disorder is not inherited from the parents. The SETBP1 gene is a cancer promoting gene, and affected children who survive past three years of age are at risk for different types of cancer.
Schinzel Giedion syndrome is a very rare disorder that affects males and females in equal numbers. The birth prevalence is unknown. There have been 50 cases reported worldwide.
A diagnosis is based on clinical findings, such as facial dysmorphism, the presence of hydronephrosis on the ultrasound and radiographic findings of skeletal malformation.
Hydronephrosis is detectable on prenatal ultrasound from week 18 to week 37.
Genetic testing for mutations in the SETBP1 gene is available to confirm the diagnosis. If a SETBP1 gene mutation is identified, it is important to confirm that the mutation is not present in in the parents.
SGS is a severe progressive syndrome and most affected individuals do not survive infancy. However, one child has been reported to live until 6 years of age and another to still be living at 15 years of age.
Treatment is based on symptoms and is more palliative or pain relieving care.
When hydronephrosis is present in patients with Schinzel Giedion syndrome, temporary drainage of the urine may be necessary. Surgery may be indicated when kidney function is compromised, pain and/or infection occur.
The definitive treatment for atrial septal defects is surgical. The hole in the septum is either sutured shut, or patched with a graft. The success rate is quite high. In ostim primum (endocardial cushion) defects, the atrioventricular valves may have to be repaired or replaced; the success rate is substantially lower in these more complex operations.
Anti-convulsant drugs such as carbamazepine, valproic acid, phenobarbital, clonazepam, ethusuximide, primidone, phenytoin, corticotropin, and corticosteroid drugs are being used to help prevent and control seizures associated with Epilepsy.
Genetic counseling may be of benefit for patients and their families. Other treatment is symptomatic and supportive.
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