Opitz G/BBB syndrome
Opitz G/BBB syndrome is a genetic condition characterized by abnormalities along the midline of the body, including wide-spaced eyes, throat defects, and genital abnormalities.
Overview
Opitz G/BBB syndrome is a genetic condition that causes several abnormalities along the midline of the body. The name "G/BBB" represents the first letters of the last names of the families first diagnosed with this disorder, while "Opitz" refers to the doctor who first described the signs and symptoms. There are two forms of the syndrome: X-linked Opitz G/BBB syndrome and autosomal dominant Opitz G/BBB syndrome. While their genetic causes and inheritance patterns differ, the signs and symptoms are generally the same.
Symptoms
Nearly everyone with Opitz G/BBB syndrome has wide-spaced eyes (hypertelorism). Other common features include:
- Throat abnormalities: Defects such as a laryngeal cleft (a gap between the trachea and esophagus) can cause difficulty swallowing or breathing, potentially leading to recurrent pneumonia or life-threatening breathing problems.
- Genital abnormalities (in males): These include the urethra opening on the underside of the penis (hypospadias), undescended testes (cryptorchidism), an underdeveloped scrotum, or a bifid scrotum.
- Developmental and cognitive issues: About 50 percent of affected individuals experience mild intellectual disability, developmental delay, delayed motor skills, speech delay, and learning difficulties. Some may exhibit features of autistic spectrum disorders.
- Clefting: About half of affected individuals have an opening in the lip (cleft lip) with or without an opening in the roof of the mouth (cleft palate).
- Distinct facial features: These may include a prominent forehead, flat nasal bridge, low-set ears, and other variations.
- Less common features: Minor heart defects, an obstruction of the anal opening (imperforate anus), and brain defects such as a small or absent connection between the left and right halves of the brain.
Causes & Risk Factors
X-linked Opitz G/BBB syndrome
This form is caused by mutations in the MID1 gene, which provides instructions for making the protein midline-1. This protein binds to microtubules, which are essential for cell shape, division, and migration. Mutations lead to decreased midline-1 function, preventing protein recycling and impairing microtubule function.
Autosomal dominant Opitz G/BBB syndrome
This form is caused by changes in chromosome 22 or mutations in the SPECC1L gene:
- Chromosome 22: Some individuals have a deletion of a small piece of chromosome 22 at the 22q11.2 region. This is often considered a form of 22q11.2 deletion syndrome.
- SPECC1L gene: This gene provides instructions for making the protein cytospin-A, which stabilizes microtubules and is necessary for cell migration, particularly during facial development. Mutations result in disorganized microtubules and impaired cell migration.
In some cases, the cause remains unknown.
Inheritance
- X-linked inheritance: Caused by MID1 gene mutations. In males, one mutated copy is sufficient to cause the condition. In females, one altered copy may lead to less severe features or no symptoms at all. Fathers cannot pass X-linked traits to their sons.
- Autosomal dominant inheritance: Caused by SPECC1L mutations or 22q11.2 deletions. One copy of the altered gene or chromosome deletion is sufficient to cause the disorder.
Affected individuals may inherit the genetic change from a parent, or the condition may result from a new mutation in people with no family history of the disorder.