Schinzel Giedion syndrome

Alternate names

Schinzel Giedion midface-retraction syndrome; SGS; Schinzel-Giedion syndrome

Definition

Schinzel-Giedion syndrome is a severe condition that is apparent at birth and affects many body systems. Signs and symptoms of this condition include distinctive facial features, neurological problems, and organ and bone abnormalities. Because of their serious health problems, most affected individuals do not survive past childhood.

Epidemiology

Schinzel-Giedion syndrome is very rare, although the exact prevalence is unknown. At least 50 cases of the condition have been reported in the scientific literature.

Cause

• Schinzel-Giedion syndrome is caused by mutations in the SETBP1 gene.
• This gene provides instructions for making a protein that attaches (binds) to certain regions of DNA to increase gene activity (expression).
• The SETBP1 protein is found throughout the body, but protein levels are highest during brain development before birth.
• During this time, nerve cells grow and divide (proliferate) and move (migrate) to their proper location in the brain.
• The SETBP1 protein is thought to control the activity of genes involved in these developmental processes.

Gene mutations

• The SETBP1 gene mutations that have been identified in Schinzel-Giedion syndrome are described as "gain-of-function" mutations because they increase the activity of the SETBP1 protein.
• Increased SETBP1 activity likely alters the expression of other genes, particularly genes involved in development before birth.
• Researchers are working to understand how mutations in the SETBP1 gene cause the signs and symptoms of Schinzel-Giedion syndrome.

Inheritance

• Schinzel-Giedion syndrome results from new mutations in the SETBP1 gene and occurs in people with no history of the disorder in their family.
• One copy of the altered gene in each cell is sufficient to cause the disorder.

Signs and symptoms

• The signs and symptoms of Schinzel Giedion syndrome (SGS) are present from birth (congenital).
• The specific features can vary among affected children, but are generally severe.
• Recurrent infections and respiratory failure are common, and most children with SGS do not live beyond a few years after birth.

Features in children with SGS may include:

• a distinctive facial appearance including a prominent forehead; "flatness" of the middle part of the face (midface retraction); and a short upturned nose
• hydronephrosis
• severe developmental delay and intellectual disability
• skeletal (bone) malformations such as short limbs; valgus or varus foot deformity (the foot is twisted outward or inward, respectively); skull abnormalities; or broad ribs
• genitourinary abnormalities such as undescended testicle(s); abnormally small penis; hypospadias; small uterus; underdeveloped inner and outer labia (folds) of the vagina; or displaced anus
• heart defects such as septal defects (affecting the dividing walls of the heart); valve abnormalities; hypoplastic ventricles (underdeveloped bottom chambers of the heart) or patent ductus arteriosus
• seizures
• visual or hearing impairment
• increased risk of tumors
• excessive hair growth (hypertrichosis)
• nail abnormalities

Diagnosis

Diagnostic criteria for the syndrome consisting of a mandatory facial phenotype involving prominent forehead, midface retraction, and short, upturned nose; developmental delay (excepting neonates); and either hydronephrosis or 2 of the 4 typical skeletal malformations, i.e., sclerotic skull base, wide occipital synchondrosis, increased cortical density or thickness, or broad ribs.

Treatment

Treatment is based on symptoms and consists of palliative care.

NIH genetic and rare disease info

• NIH info on Schinzel Giedion syndrome

Schinzel Giedion syndrome is a rare disease.