"Schinzel-Giedion Syndrome" – What Is It?
Schinzel-Giedion syndrome (SGS) is a disease caused by mutations, i.e., genetic changes in the SETBP1 gene. It is characterized by severe developmental delay, a characteristic facial appearance, and several congenital anomalies, mainly affecting the skeleton, the urogenital tract, the kidneys, and the heart. There is also an increased risk of various cancers. Patients usually die within the first ten years of life.
How Is "Schinzel-Giedion Syndrome" Diagnosed?
Clinical Diagnostic Criteria
Schinzel-Giedion syndrome can be diagnosed based on specific existing changes or abnormalities. The symptoms are divided into mandatory criteria, which must be fulfilled for the diagnosis, and additional criteria, which must be fulfilled.
Mandatory Criteria:
- Developmental delay (except newborns)
- Characteristic shape of the face
- Prominent forehead
- Sunken midface
- Short, upturned nose
Additionally One of the Following Criteria:
- Urinary stasis kidney (water-sac kidney)
- 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
In addition to the clinical diagnosis, the diagnosis of Schinzel-Giedion syndrome is confirmed by detecting a mutation, i.e., a genetic change in the SETBP1 gene.
What Is the Risk of Cancer?
Malignant tumors have been described in individual patients. These include germ cell tumors (mostly tumors of the ovaries), primitive neuroectodermal tumors (tumors that develop from the precursor structures of the nervous system), an ependymoma (tumor of the brain and spinal cord), a hepatoblastoma (liver tumor) and a malignant retroperitoneal tumor (located behind the abdominal cavity). The risk of cancer is not yet known but appears to be high and may be between 10% and 15%.
In addition to the increased risk of cancer, Schinzel-Giedion syndrome can manifest itself with a variety of symptoms, which are described below:
Prenatal
Before birth, the child may have a urinary stasis kidney (water-sac kidney), which is usually present on both sides and varies in severity. There may also be an above-average amount of amniotic fluid.
Changes to the Face
The characteristic face shape consists of a sunken midface (present in all patients), large anterior fontanel, prominent bulging forehead, short and upturned nose, wide eye distance, wide mouth with large tongue, short neck, low-set ears with deformities, and conspicuously thick hair. The various features vary in intensity from patient to patient.
Organ Manifestations
In more than 90% of patients, a urinary stasis kidney is found, ranging from mild dilatation of the renal pelvis to severe urinary stasis kidney.
The majority of patients (76%) have genital anomalies, which usually manifest as underdeveloped genital organs and malformed urethral orifices.
Just under half of patients have heart anomalies. These can include heart valve defects, underdeveloped heart chambers, defects in the cardiac septum, or an incorrectly maintained connection between the aorta and pulmonary artery after birth.
Around a quarter of patients have an obstruction or narrowing of the posterior nasal opening.
Neurological Abnormalities
Severe developmental delay is present in the majority of patients. In addition, seizures are frequently described (70%), which are usually difficult to break through. Visual and hearing impairments may also occur. Imaging of the head may reveal various abnormalities. About half of the patients fail to thrive.
Manifestations on Arms and Legs
Frequently observed abnormalities include shortened arms and legs, severely curved nails, bow legs or knock-knees, and a four-fingered groove.
Abnormalities of the Skeleton
Imaging often shows broad ribs, a thickened, dense bone surface on the bones of the arms and legs, and underdeveloped extremities on the hands and feet. In addition, a hardened skull base and wide open cranial sutures are frequently described.
What Is Known About the Development of "Schinzel-Giedion Syndrome "?
Schinzel-Giedion syndrome is caused by mutations, i.e., genetic changes in the SETBP1 gene. This gene codes for the SET-binding protein-1, which is necessary for the replication of DNA, i.e., the genetic material, in our body.
If the SETBP1 gene is present in an altered form, the SET-binding protein-1 is also not produced correctly and can no longer fulfill its actual function. This can lead to the incorrect development of various structures in our body.
Schinzel-Giedion syndrome occurs in less than one in 1,000,000 live births and can be passed on from parents to their children. The inheritance is autosomal dominant. In almost all cases, however, it is a spontaneous or new mutation known as a de novo mutation.
Is There Any Form of Treatment Available?
Given the many possible manifestations, treatment should always be symptom-oriented and carried out in collaboration with various specialist disciplines.
Diagnosis of " Schinzel-Giedion Syndrome" What's Next?
If you have been diagnosed with this cancer predisposition syndrome, it is important to see a specialist. The following section explains whether cancer screening tests or other measures are needed and how they should be carried out. We also give you some valuable tips on what you can do yourself. If you have any questions, please do not hesitate to contact us or your doctor.
Diagnosis of " Schinzel-Giedion Syndrome" What's Next?
If you have been diagnosed with this cancer predisposition syndrome, it is important to see a specialist. The following section explains whether cancer screening tests or other measures are needed and how they should be carried out. We also give you some valuable tips on what you can do yourself. If you have any questions, please do not hesitate to contact us or your doctor.
Medical Measures for Early Detection
Patients and their families should be made aware of the presumably high cancer risk of 10%-15%.
During basic diagnostics, special attention should be paid to the risk of congenital tumors. For skeletal, neurological, and renal abnormalities, this diagnosis should include imaging of the spine, abdomen, and pelvis.
In patients with severe symptoms, determining the tumor markers AFP and β-HCG in the blood can be helpful in addition to a basic blood test.
In milder cases, regular determination of AFP and β-HCG in the blood and regular ultrasound examinations of the abdomen and pelvis should also be considered.
Schinzel-Giedion Syndrome – What You Can Do Yourself
You Should Pay Attention to This
You should consult a doctor as soon as changes in urination or back pain occur. Abdominal pain, fatigue, or tiredness should also be noticed and reported to a doctor. You should also consult a doctor if you notice any other new abnormalities or complaints, such as impaired vision or changes in hearing.
Further Information
Unfortunately, we are not yet aware of any self-help groups for patients with Schinzel-Giedion syndrome. As soon as we have new information, we will add it here. However, patients can also register for the CPS registry at any time or have this done by their doctors in charge.
Any further questions?
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