Opitz Syndrome Health Article

Definition

Opitz syndrome is a heterogeneous genetic condition characterized by a range of midline birth defects such as hypertelorism, clefts in the lips and larynx, heart defects, hypospadias and agenesis of the corpus callosum.

Description

Opitz syndrome or Opitz G/BBB syndrome, as it is sometimes called, includes G syndrome and BBB syndrome, which were originally thought to be two different syndromes. In 1969, Dr. John Opitz described two similar conditions that he called G syndrome and BBB syndrome. G syndrome was named after one family affected with this syndrome whose last name began with the initial G and BBB syndrome was named after the surname of three different families. Subsequent research suggested that these two conditions were one disorder but researchers could not agree on how this disorder was inherited. It wasn't until 1995 that Dr. Nathaniel Robin and his colleagues demonstrated that Opitz syndrome had both X-linked and autosomal dominant forms.

Opitz syndrome is a complex condition that has many symptoms, most of which affect organs along the midline of the body such as clefts in the lip and larynx, heart defects, hypospadias and agenesis of the corpus callosum. Opitz syndrome has variable expressivity, which means that different people with the disorder can have different symptoms. This condition also has decreased penetrance, which means that not all people who inherit this disorder will have symptoms.

Genetic profile

Opitz syndrome is a genetically heterogeneous condition. There appear to be at least two to three genes that can cause Opitz syndrome when changed (mutated) or deleted. Opitz syndrome can be caused by changes in genes found on the X chromosome (X-linked) and changes in or deletion of a gene found on chromosome 22 (autosomal dominant).

Chromosomes, genes and proteins

Each cell of the body, except for the egg and sperm cells, contains 23 pairs of chromosomes—46 chromosomes in total. The egg and sperm cells contain only one of each type of chromosome and therefore contain 23 chromosomes in total. Males and females have 22 pairs of chromosomes, called the autosomes, numbered one to twenty-two in order of decreasing size. The other pair of chromosomes, called the sex chromosomes, determines the sex of the individual. Women possess two identical chromosomes called the X chromosomes while men possess one X chromosome and one Y chromosome. Since every egg cell contains an X chromosome, women pass on the X chromosome to their daughters and sons. Some sperm cells contain an X chromosome and some sperm cells contain a Y chromosome. Men pass the X chromosome on to their daughters and the Y chromosome on to their sons. Each type of chromosome contains different genes that are found at specific locations along the chromosome. Men and women inherit two of each type of autosomal gene since they inherit two of each type of autosome. Women inherit two of each type of X-linked gene since they possess two X chromosomes. Men inherit only one of each X-linked gene since they posses only one X chromosome.

Each gene contains the instructions for the production of a particular protein. The proteins produced by genes have many functions and work together to create the traits of the human body such as hair and eye color and are involved in controlling the basic functions of the human body. Changes or deletions of genes can cause them to produce abnormal protein, less protein or no protein. This can prevent the protein from functioning normally.

Autosomal dominant Opitz syndrome

The gene responsible for the autosomal dominant form of Opitz syndrome has not been discovered yet, but it appears to result from a deletion in a segment of chromosome 22 containing the Opitz gene or a change in the gene responsible for Opitz syndrome. In some cases the deletion or gene change is inherited from either the mother or father who have the gene change or deletion in one chromosome 22 in their somatic cells. The other chromosome 22 found in each of their somatic cells is normal. Some of their egg or sperm cells contain the gene change or deletion in chromosome 22 and some contain a normal chromosome 22. In other cases the deletion has occurred spontaneously during conception or is only found in some of the egg or sperm cells of either parent but not found in the other cells of their body.

Parents who have had a child with an autosomal dominant form of Opitz syndrome may or may not be at increased risk for having other affected children. If one of the parents is diagnosed with Opitz syndrome then each of their children has a 50% chance of inheriting the condition. If neither parent has symptoms of Opitz syndrome nor possesses a deletion, then it becomes more difficult to assess their chances of having other affected children.

In many cases they would not be at increased risk since the gene alteration occurred spontaneously in the embryo during conception. It is possible, however, that one of the parents is a carrier, meaning they possess a change in the autosomal dominant Opitz gene but do not have any obvious symptoms. This parent's children would each have a 50% chance of inheriting the Opitz gene.