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Opitz G/BBB syndrome is a genetic condition that affects several structures along the midline of the body. The most common features of this condition are wide-spaced eyes (hypertelorism); defects of the larynx, trachea, and/or esophagus causing breathing problems and difficulty swallowing (dysphagia); and in males, the urethra opening on the underside of the penis (hypospadias).
Mild intellectual disability occurs in fewer than 50 percent of people with Opitz G/BBB syndrome, most likely caused by structural defects in the brain. About half of affected individuals also have cleft lip with or without a cleft palate (an opening in the roof of the mouth). Some have cleft palate alone. Heart defects, an obstruction of the anal opening (imperforate anus), and brain defects such as an absence of the tissue connecting the left and right halves of the brain (corpus callosum) occur in less than 50 percent of those affected. Facial abnormalities that may be seen in this disorder include a flat nasal bridge, thin upper lip, and low set ears. These features vary among affected individuals, even within the same family.
There are two forms of Opitz G/BBB syndrome, which are distinguished by their genetic causes and patterns of inheritance. The X-linked form of Opitz G/BBB syndrome is caused by a mutation in a specific gene, MID1, on the X chromosome. Autosomal dominant Opitz G/BBB syndrome is caused by a mutation in an as-yet unidentified gene on chromosome 22.
The signs and symptoms of the autosomal dominant form of the condition are comparable to those seen in the X-linked form. The X-linked form of Opitz G/BBB syndrome tends to include cleft lip with or without cleft palate, while cleft palate alone is more common in the autosomal dominant form. Females with X-linked Opitz G/BBB syndrome are usually mildly affected, as hypertelorism may be the only sign of the disorder.
X-linked Opitz G/BBB syndrome is thought to affect 1 in 50,000 to 100,000 males.
The incidence of autosomal dominant Opitz G/BBB syndrome is unknown. It is part of a larger condition known as 22q11.2 deletion syndrome, which is estimated to affect 1 in 4,000 people.
Opitz G/BBB syndrome is related to chromosome 22.
Mutations in the MID1 gene cause Opitz G/BBB syndrome.
The X-linked form of Opitz G/BBB syndrome is caused by mutations in the MID1 gene. The MID1 gene provides instructions for making a protein called midin. This protein helps regulate the function of microtubules, which are rigid, hollow fibers that make up the cell's structural framework (the cytoskeleton). Microtubules help cells maintain their shape, assist in the process of cell division, and are essential for the transport of materials within cells.
The MID1 gene is a member of a group of genes called the TRIM (tripartite motif) family. The proteins produced from this large family of genes are involved in many cellular activities. Primarily, TRIM proteins play a role in the cell machinery that breaks down (degrades) unwanted proteins.
As part of its protein degrading function, midin is responsible for the breakdown of an enzyme called protein phosphatase 2A (PP2A). This enzyme regulates a number of microtubule-associated proteins, as well as other proteins involved in critical cellular processes such as cell division. When a mutation causes midin to malfunction, PP2A accumulates in the cell and alters the function of the microtubule-associated proteins. These changes disrupt microtubule function, and cells can have difficulty dividing properly. Nonfunctional midin binds with itself (aggregates) and forms protein clumps in the cells. It is unclear how these changes disrupt normal development and cause the birth defects associated with Opitz G/BBB syndrome.
Some people who have a family history of X-linked Opitz G/BBB syndrome have no detectable MID1 mutation. The reason for this is not yet known, although some researchers have suggested the involvement of other unknown genes.
The autosomal dominant form of Opitz G/BBB syndrome is caused by a deletion of a small piece of chromosome 22, specifically 22q11.2, which is why researchers consider this condition to be part of 22q11.2 deletion syndrome. It is not yet known which deleted gene(s) cause the signs and symptoms of Opitz G/BBB syndrome.
Changes involving this chromosome are associated with Opitz G/BBB syndrome.
Changes in this gene are associated with Opitz G/BBB syndrome.
Opitz G/BBB syndrome often has an X-linked dominant pattern of inheritance, which means one copy of an altered gene in each cell is sufficient to cause the disorder. A condition is considered X-linked if the mutated gene that causes the disorder is located on the X chromosome, one of the two sex chromosomes. In most cases, males experience more severe symptoms of the disorder than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons. In some cases, an affected person inherits a MID1 mutation from an affected parent. Other cases may result from new mutations in this gene. These cases occur in people with no history of the disorder in their family.
Researchers have also described an autosomal dominant form of Opitz G/BBB syndrome caused by a deletion in one copy of chromosome 22 in each cell. In some cases, an affected person inherits the chromosome with a deleted segment from a parent. Other cases result from a deletion that occurs during the formation of reproductive cells (eggs and sperm) or in early fetal development. These cases occur in people with no history of the disorder in their family. Males and females with the autosomal dominant form of Opitz G/BBB syndrome usually have the same severity of symptoms.
These resources address the diagnosis or management of Opitz G/BBB syndrome and may include treatment providers.
You might also find information on the diagnosis or management of Opitz G/BBB syndrome in Educational resources (http://www.ghr.nlm.nih.gov/condition/opitz-g-bbb-syndrome/show/Educational+resources) and Patient support (http://www.ghr.nlm.nih.gov/condition/opitz-g-bbb-syndrome/show/Patient+support).
General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).
To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.
You may find the following resources about Opitz G/BBB syndrome helpful. These materials are written for the general public.
You may also be interested in these resources, which are designed for healthcare professionals and researchers.
For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.
Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).
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You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).
The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.