Schinzel-Giedion syndrome - SETBP1 gene.
Schinzel-Giedion syndrome or Schinzel-Giedion middle face retraction syndrome, is a serious condition that manifests at birth and affects many body systems including distinctive facial features, neurological problems and abnormalities in organs and bones.
Signs related to this process generally include distinctive facial features such as retraction of the middle face, wide or bulky forehead, ocular hypertelorism, a short and upward nose and, a wide mouth with macroglossia; broader fontanel at birth; short neck; low implant ears; alacrimia; hypertrichosis; severe developmental delay; severe feeding problems; seizures; visual or hearing impairment; and sleeping apnea. Other signs of Schinzel-Giedion syndrome are abnormalities of the organs, such as the heart (problems with the heart valves, ventricles or septum), the kidneys (hydronephrosis) or the genitals (hypoplasia or hypospadias in men). Bone abnormalities generally include sclerotic bones or occipital synchondrosis at the base of the skull, wide ribs, abnormal clavicles, feet that turn inward and upward, shortened bones in the arms or legs, or hypoplastic distal phalanges. In addition, individuals with Schinzel-Giedion syndrome have an increased risk of developing neuroepithelial tumors.
Schinzel-Giedion syndrome is due to mutations in the SETBP1 (SET binding protein 1) gene, located on the long arm of chromosome 18 (18q12.3), which encodes the SET 1 binding protein (SETBP1). This protein is found in cells throughout the body where it binds to certain regions of DNA to increase gene expression and regulate protein production. It is believed that the SETBP1 protein controls the genes that participate in brain development before birth.
At least 16 mutations in the SETBP1 gene have been identified in children with Schinzel-Giedion syndrome. The identified mutations generally occur in the gene exon 4 and consist of aminoacid changes in the SETBP1 protein. Although the exact mechanism that causes this condition is still unclear, these mutations increase the activity of the SETBP1 protein, which alters the expression of other genes, particularly the genes involved in development before birth.
Schinzel-Giedion syndrome is due to mutations in the SETBP1 gene that occur in people with no history of the process in their family. A copy of the altered gene in each cell is sufficient to cause the alteration.
Tests performed in IVAMI: in IVAMI we detect mutations associated with Schinzel-Giedion syndrome, by complete PCR amplification of exons of the SETBP1 gene, and subsequent sequencing.
Recommended samples: blood taken with EDTA for separation of blood leukocytes, or card impregnated with dried blood sample (IVAMI can mail the card to deposit the blood sample).