X-linked Opitz G/BBB syndrome

National Organization for Rare Disorders, Inc.

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It is possible that the main title of the report X-linked Opitz G/BBB syndrome is not the name you expected. Please check the synonyms listing to find the alternate name(s) and disorder subdivision(s) covered by this report.


  • XLOS
  • Opitz BBBG syndrome
  • Opitz-G syndrome
  • telecanthus-hypospadius syndrome (obsolete)
  • hypertelorism-hypospadius syndrome (obsolete)

Disorder Subdivisions

  • None

General Discussion

X-linked Opitz G/BBB syndrome is a rare genetic disorder characterized by facial anomalies, respiratory and genitourinary abnormalities and other midline defects as well as developmental delay or mental retardation. There is a wide variation in severity of this condition, even among members of the same family. X-linked Opitz G/BBB syndrome is an X-linked genetic condition associated with alterations (mutations) in the MID1 gene.


X-linked Opitz G/BBB syndrome is a rare genetic disorder mainly characterized by facial anomalies, respiratory and genitourinary abnormalities as well as developmental delay or mental retardation.

Facial anomalies may include widely spaced eyes (hypertelorism), a prominent forehead, widow's peak, broad nasal bridge, nostrils that are tipped forward, and cleft lip/palate.

Respiratory abnormalities can include laryngo-esophageal clefts that result in difficulty swallowing and breathing. Genitourinary problems can include abnormal placement of the urethra in the penis (hypospadias), undescended testes and sometimes kidney abnormalities. Anal defects may also be present and include absent or mis-positioned anal opening. Congenital heart defects such as ventral septal defects and atrial septal defects as well as brain defects such as agenesis or hypoplasia of the brain region that connects the two hemispheres (corpus callosum) and hypoplasia of the cerebellum also in the context of more complex defects such as Dandy-Walker malformation.

There is a wide variation in the presentation of the clinical signs and in the severity of this condition, even among members of the same family.

Approximately 50% of affected males have developmental delay or mental retardation. Carrier females usually have hypertelorism only.


X-linked Opitz G/BBB syndrome is inherited as an X-linked genetic condition. X-linked genetic disorders are conditions caused by an abnormal gene on the X chromosome and occur mostly in males. Males have one X chromosome that is inherited from their mother and if a male inherits an X chromosome that contains a disease gene he will develop the disease. Females that have a disease gene present on one of their X chromosomes are carriers for that disorder. Carrier females usually do not display clinical signs because females have two X chromosomes and one is inactivated so that the genes on that chromosome are nonfunctioning. It is usually the X chromosome with the abnormal gene that is inactivated.

Female carriers of an X-linked disorder have a 25% chance with each pregnancy to have a carrier daughter like themselves, a 25% chance to have a non-carrier daughter, a 25% chance to have a son affected with the disease and a 25% chance to have an unaffected son.

Males with X-linked disorders pass the disease gene to all of their daughters who will be carriers. A male cannot pass an X-linked gene to his sons because males always pass their Y chromosome to male offspring.

The MID1 gene is the only gene known to be associated with Opitz G/BBB syndrome.

Affected Populations

The prevalence of Opitz G/BBB syndrome is estimated to be 1/50,000-1/100,000 males.

Standard Therapies


The diagnosis of Opitz G/BBB syndrome is usually made by clinical findings. It is not possible to distinguish this condition from chromosome 22q11.2 deletion syndrome (autosomal dominant Opitz G/BBB syndrome) based on physical features alone. Diagnosis of X-linked Opitz Syndrome can be done by way of inheritance and by molecular genetic testing for mutations in the MID1 gene that is available (15%-45% of affected males have been found to have a mutation).

Widely spaced eyes and cleft lip and palate associated with this condition can sometimes be visualized with prenatal ultrasound.


X-linked Opitz G/BBB syndrome is treated by a team of specialists including surgeons, speech therapists, neuropsychologists and early intervention specialists. Regular assessment of hearing is recommended for affected children with cleft lip and palate.

Investigational Therapies

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. Government funding, and some supported by private industry, are posted on this government web site.

For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222

TTY: (866) 411-1010

Email: prpl@cc.nih.gov

For information about clinical trials sponsored by private sources, contact:




Opitz JM. GBBB Syndrome (Opitz Syndrome). In: The NORD Guide to Rare Disorders, Philadelphia: Lippincott, Williams and Wilkins, 2003:198-99.


Fontanella B, Russolillo G, Meroni G. MID1 mutations in patients with X-linked Opitz G/BBB Syndrome. Human Mutation, 2008 May; 29(5):584-94.

So J, Suckow V, Kijas Z, et al. Mild phenotypes in a series of patients with Opitz G/BBB syndrome with MID1 mutations. Am J Med Genet 2005;132A:1-7.

DeFalco F, Cainarca S, Andolfi G, et al. X-linked Opitz syndrome: novel mutations in the MID1 gene and redefinition of the clinical spectrum. Am J Med Genet. 2003;120A:222-228.

Cox TC, Allen LR, Cox LL, et al. New mutations in MID1 provide support for loss of function as the cause of X-linked Opitz syndrome. Hum. Mol. Genet. 2000;17: 2553-2562.

Robin NH, Opitz JM, Muenke M. Opitz G/BBB syndrome:clinical comparisons of families linked to Xp22 and 22q, and a review of the literature. Am J Med Genet 1996;62:305-317.

Robin NH, Feldman GJ, Aronson AL, et al. Opitz syndrome is genetically heterogeneous with one locus on Xp22 and a second locus on 22q11.2. Nature Genet. 1995;11:459-61.

Verloes A, David A, Odent S, et al. Opitz GBBB syndrome: chromosomal evidence of an X-linked form. Am J Med Genet. 1995;59:123-28.


Meroni G. (Updated 7/28/11). X-Linked Opitz G/BBB Syndrome. In GeneReviews at Genetests: Medical Genetics Information Resource (database online). Copyright, University of Washington, Seattle. 1997-2008. Available at http://www.genetests.org Accessed: January 12, 2012.

McKusick VA, ed. Online Mendelian Inheritance in Man (OMIM). Baltimore. MD: The Johns Hopkins University; Entry No:30000; Last Update: 10/31/08. http://omim.org/entry/300000 Accessed: January 12, 2012.


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For a Complete Report

This is an abstract of a report from the National Organization for Rare Disorders, Inc.® (NORD). Cigna members can access the complete report by logging into myCigna.com. For non-Cigna members, a copy of the complete report can be obtained for a small fee by visiting the NORD website. The complete report contains additional information including symptoms, causes, affected population, related disorders, standard and investigational treatments (if available), and references from medical literature. For a full-text version of this topic, see http://www.rarediseases.org/search/rdblist.html.