Bohring-Opitz syndrome is a rare condition that affects the development of many parts of the body.
People with Bohring-Opitz syndrome have abnormal development of the head. They often have a small head size (microcephaly) and a skull abnormality called trigonocephaly, which gives the forehead a pointed appearance. Brain abnormalities result in profound to severe intellectual disability and developmental delay in affected individuals. Many people with this condition experience seizures.
Characteristic eye problems occur in people with Bohring-Opitz syndrome. They may have protruding eyes (exophthalmos), eyes that do not point in the same direction (strabismus), widely spaced eyes (hypertelorism), or outside corners of the eyes that point upward (upslanting palpebral fissures). Affected individuals may have nearsightedness (myopia) or abnormalities in the light-sensitive tissue at the back of the eye (the retina) or the nerves that carry information from the eyes to the brain (optic nerves), which can impair vision.
Additional facial features of Bohring-Opitz syndrome can include a flat nasal bridge, nostrils that open to the front rather than downward (anteverted nares), a high arch or opening in the roof of the mouth (high arched or cleft palate), a small lower jaw (micrognathia), low-set ears that are rotated backward, a red birthmark called a port-wine stain on the forehead, and a low frontal hairline with excessive facial hair (hirsutism).
Individuals with Bohring-Opitz syndrome have poor growth before birth (intrauterine growth retardation). During infancy they experience a failure to gain weight and grow at the expected rate (failure to thrive) and often have feeding difficulties.
People with this condition often have characteristic positioning of the upper body, known as Bohring-Opitz syndrome posture. This posture consists of slouching shoulders, permanently bent elbows and wrists, and a hand deformity in which the wrist or all of the fingers are angled outward toward the fifth finger (ulnar deviation). Joint deformities called contractures in the knees, hips, or other joints that are apparent at birth and abnormal muscle tone may also occur in this condition. Affected individuals can have recurrent infections and heart, kidney, or genital abnormalities. In rare cases, a childhood form of kidney cancer known as Wilms tumor can develop.
Some individuals with Bohring-Opitz syndrome do not survive past early childhood, while others live into adolescence or early adulthood. The most common causes of death are recurrent episodes of an abnormally slow heartbeat (bradycardia), which eventually leads to a fatal lack of oxygen in the body's organs and tissues; abnormalities of the throat and airways that cause short pauses in breathing (obstructive apnea); and lung infections.
Bohring-Opitz syndrome is thought to be a rare condition, although its exact prevalence is unknown. More than 40 affected individuals have been described in the scientific literature.
Bohring-Opitz syndrome is caused by mutations in the ASXL1 gene. This gene provides instructions for making a protein that is involved in a process known as chromatin remodeling. Chromatin is the complex of DNA and proteins that packages DNA into chromosomes. The structure of chromatin can be changed (remodeled) to alter how tightly DNA is packaged. Through its role in chromatin remodeling, the ASXL1 gene regulates the activity (expression) of many genes, including a group of genes known as HOX genes, which play important roles in development before birth. The ASXL1 protein can turn on (activate) or turn off (repress) HOX genes depending on when they are needed.
It is unclear how ASXL1 gene mutations cause the signs and symptoms of Bohring-Opitz syndrome. ASXL1 gene mutations reduce the amount of functional ASXL1 protein available, which likely disrupts the regulation of the activity of HOX genes and other genes during development. Altered activity of these genes probably leads to the neurological and physical features of this condition.
Bohring-Opitz syndrome is considered an autosomal dominant condition, which means one copy of the altered gene in each cell is sufficient to cause the disorder.
Most cases of the condition result from new (de novo) mutations in the gene that occur during the formation of reproductive cells (eggs or sperm) or in early embryonic development. These cases occur in people with no history of the disorder in their family. Because the condition is so severe, no one with Bohring-Opitz syndrome has been known to have children.
- Bohring syndrome
- C-like syndrome
- Oberklaid-Danks syndrome
- Opitz trigonocephaly-like syndrome
- Boston Children's Hospital: Metopic Synostosis (Trigonocephaly) Symptoms & Causes
- Centers for Disease Control and Prevention: Facts About Developmental Disabilities
- Centers for Disease Control and Prevention: Facts About Microcephaly
- Disease InfoSearch: C-Like Syndrome
- Johns Hopkins Medicine: Failure to Thrive
- KidsHealth from Nemours: Failure to Thrive
- MalaCards: bohring-opitz syndrome
- Oregon Health Sciences University: Metopic Synostosis
- Orphanet: Bohring-Opitz syndrome