Opitz Syndrome Health Article

X-linked Opitz syndrome

Some people with the X-linked form of Opitz syndrome have a change (mutation) in a gene found on the X chromosome called the MID1 (midline1) gene. Changes in another X-linked gene called the MID2 gene may also cause Opitz syndrome in some cases. It is believed that the MID genes produce proteins involved in the development of midline organs. Changes in the MID gene prevent the production of enough normal protein for normal organ development.

The X-linked form of Opitz syndrome is inherited differently by men and woman. A woman with an X-linked form of Opitz syndrome has typically inherited a changed MID gene from her mother and a changed MID gene from her father. This occurs very infrequently. All of this woman's sons will have Opitz syndrome and all of her daughters will be carriers for Opitz syndrome. Only women can be carriers for Opitz syndrome since carriers possess one changed MID gene and one unchanged MID gene. Most carriers for the X-linked form of Opitz syndrome do not have symptoms since one normal MID gene is usually sufficient to promote normal development. Some carriers do have symptoms but they tend to be very mild. Daughters of carriers for Opitz syndrome have a 50% chance of being carriers and sons have a 50% chance of being affected with Opitz syndrome. A man with an X-linked form of Opitz syndrome will have normal sons but all of his daughters will be carriers.

Demographics

Opitz syndrome is a rare disorder that appears to affect all ethnic groups. The frequency of this disorder is unknown since people with this disorder exhibit a wide range of symptoms, making it difficult to diagnose and many possess mild or non-detectable symptoms.

Signs and symptoms

People with Opitz syndrome exhibit a wide range of medical problems and in some cases may not exhibit any detectable symptoms. This may be due in part to the genetic heterogeneity of this condition. Even people with Opitz syndrome who are from the same family can have different problems. This may mean there are other genetic and non-genetic factors that influence the development of symptoms in individuals who have inherited a changed or deleted Opitz gene. Most individuals with Opitz syndrome only have a few symptoms of the disorder such as wide set eyes and a broad prominent forehead. Opitz syndrome can, however, affect many of the organs and structures of the body and primarily affects the development of midline organs. The most common symptoms are: hypertelorism (wide-spaced eyes), broad prominent forehead, heart defects, hypospadias (urinary opening of the penis present on the underside of the penis instead of its normal location at the tip), undescended testicles, an abnormality of the anal opening, agenesis of the corpus callosum (absence of the tissue which connects the two sides of the brain), cleft lip, and clefts and abnormalities of the pharynx (throat) and larynx (voice-box), trachea (wind-pipe) and esophagus.

People with Opitz syndrome usually have a distinctive look to the face such as a broad prominent forehead, cleft lip, wide set eyes that may be crossed, wide noses with upturned nostrils, small chins or jaws, malformed ears, crowded, absent or misplaced teeth and hair that may form a "widow's peak." In many cases the head may appear large or small and out of proportion to the rest of the body.

Often people with Opitz syndrome have difficulties swallowing because of abnormalities in the pharynx, larynx, trachea, or esophagus. This can sometimes result in food entering the trachea instead of the esophagus, which can cause damage to the lungs and pneumonia, and can sometimes be fatal in small infants. Abnormalities in the trachea can sometimes make breathing difficult and may result in a hoarse or weak voice and wheezing.

Both males and females may have abnormal genitals and abnormalities in the anal opening. Males can have hypospadias and undescended testicles and girls may have minor malformation of their external genitalia. Heart defects are also often present and abnormalities of the kidney can be present as well. Intelligence is usually normal but mild mental retardation can sometimes be present. Twins appear more common in families affected with Opitz syndrome.

Males and females with the dominant form of Opitz syndrome are equally likely to have symptoms whereas carrier females with the X-linked form of Opitz syndrome are less likely to have symptoms then males with the condition. In general, males with the X-linked form of Opitz syndrome tend to be more severely affected than females and males with the autosomal dominant form of Opitz syndrome. People with X-linked Opitz syndrome and dominant Opitz syndrome generally appear to exhibit the same range of symptoms. The only known exceptions are upturned nostrils and clefts at the back of throat, which appear to only occur in people with X-linked Opitz syndrome.