What is Schinzel-Giedion syndrome?

Schinzel-Giedion syndrome is a disease caused by mutations – or genetic changes – in the SETBP1 gene. It is characterized by severe developmental delays, a distinctive shape of the face, and multiple congenital anomalies, mainly of the skeleton, urogenital tract, kidneys, and heart. In addition, there is also an increased risk of various malignant diseases. Patients usually die within the first ten years of life.

How is Schinzel-Giedion syndrome diagnosed?

Clinical Diagnostic Criteria

The diagnosis of “Schinzel-Giedion syndrome” can be made on the basis of specific existing changes or anomalies. Its symptoms are classified as obligatory criteria, which need to be met to make the diagnosis, and additional criteria, of which only one needs to be met.

Obligatory Criteria:

  • Developmental delays (except in newborns)

  • Distinctive shape of the face

    • Prominent forehead
    • Sunken midface
    • Short upturned nose

In Addition, One of the Following Criteria:

  • Build-up of urine in the kidney (hydronephrosis)

  • Two of the following typical skeletal changes:

    • Hardened skull base
    • Wide-open cranial sutures
    • Increased density or thickness of the bone surface
    • Wide ribs

Genetic Diagnostics

Along with the clinical diagnosis, the diagnosis of “Schinzel-Giedion syndrome” is also confirmed by detection of a mutation – or genetic change – in the SETBP1 gene.

What is the risk of cancer?

Malignant tumors have been described in a few patients, e.g. germ cell tumors (usually tumors of the ovaries), primitive neuroectodermal tumors (tumors that develop from the precursor structures of the nervous system), one ependymoma (a tumor of the brain and spinal cord), one hepatoblastoma (liver tumor), and one malignant retroperitoneal tumor (located behind the abdominal cavity). While the risk of cancer is not yet known, it appears to be high and may be between 10% and 15%.

Along with the increased risk of cancer, it is possible for a wide variety of symptoms to manifest as part of Schinzel-Giedion syndrome as presented below:

Before Birth

Before birth, a child may exhibit a build-up of urine in the kidney (hydronephrosis) – usually on both sides and to different extent. In addition, there may be an excessively large amount of amniotic fluid.

Changes in the Face

The distinctive shape of the face consists of a sunken midface (present in all patients), a large frontal fontanel, a prominent bulging forehead, a short upturned nose, a large distance between the eyes, a broad mouth with a large tongue, a short neck, low-lying ears with malformations, and excessive hair. These different characteristics vary from patient to patient.

Organ Manifestations

A build-up of urine in the kidney can be found in over 90% of patients, ranging from mild stretching of the renal pelvis (pyelectasis) to a severe build-up of urine in the kidney (hydronephrosis).

The majority of patients (76%) exhibit genital anomalies, which generally present themselves as underdeveloped genitals and a displaced aperture of the urethra.

Heart anomalies can be found in nearly half of the patients, including heart valve defects, underdeveloped ventricles, defects of the cardiac septum, or the inappropriate persistence of a connection between the aorta and pulmonary artery.

In approximately one quarter of patients, the posterior nasal opening is closed or constricted.

Neurological Anomalies

Severe developmental delays can be detected in the majority of patients. In addition, cramping seizures are frequently described (70%) that are usually difficult to interrupt. Visual and hearing impairment may occur as well. Imaging of the head can reveal various anomalies. Around half of the patients exhibit a failure to thrive.

Manifestations in the Arms and Legs

The most commonly observed anomalies include shortened arms and legs, extremely curved nails, bow legs or knock knees, and a simian crease.

Anomalies of the Skeleton

In those affected, imaging frequently reveals wide ribs, a thickened, dense surface of the bones in the arms and legs, and underdeveloped tips of the hands and feet. It is also common for a hardened skull base and wide-open cranial sutures to be described.

What causes Schinzel-Giedion syndrome?

Schinzel-Giedion syndrome is caused by mutations – or genetic changes – in the SETBP1 gene. This gene encodes for the SET-binding protein, which is necessary for the amplification of DNA – or genetic material – in our body.

Now if the SETBP1 gene is altered, the SET-binding protein will not be produced properly and will no longer be able to perform its normal function. This can result in the defective development of various structures in our body.

Schinzel-Giedion syndrome occurs in approximately one in 1.000.000 people and can be passed on by parents to their children. In these cases, it is inherited as an autosomal dominant disease. However, nearly all cases involve a spontaneous or new mutation, called a de novo mutation.

Is there a treatment?

In light of the large number of potential manifestations, treatment should always be symptom-orientated and involve the collaboration of different specialist disciplines.

Surveillance Recommendations for the Early Detection of Cancer

Surveillance Recommendations

Patients and their families should be informed of the presumed high risk of developing cancer of 10-15%.

During basic diagnostics, the risk of congenital tumors should always be borne in mind. With regard to anomalies of the skeleton, nerves, and kidneys, such diagnostics should include imaging of the spine, abdomen, and pelvis.

In patients with severe symptoms, determining the level of the AFP and β-HCG tumor markers in blood may well be helpful in addition to a basic blood analysis.

For milder progressions, regularly determining AFP and β-HCG levels in the blood and conducting regular ultrasounds of the abdomen and pelvis should be considered as well.

Self-Care and Support

What should I pay special attention to?

You should see a doctor as soon as changes in urinating or back pain occur. Moreover, abdominal pain, weariness, or fatigue should be noted and reported to a doctor as well. You should likewise go to a doctor if new anomalies or complaints such as limitations or changes in vision or hearing develop.

Support Groups and Additional Information

Unfortunately, we are as yet unaware of any existing support groups for patients with Schinzel-Giedion syndrome. We will add new information as it becomes available.