The group of characteristics referred to as Pitt-Hopkins syndrome results when one of the two copies of the TCF4 gene is non-functional. One copy of the TCF4 gene is made non-functional when there is a genetic mutation in the gene or when a part or all of the gene has been deleted. This type of genetic change is new to the person with Pitt-Hopkins and is not inherited from a parent. In addition to the TCF4 deletion, some individuals with Pitt-Hopkins syndrome have other deleted adjacent genes. These individuals can then have features of 18q- in addition to the features of Pitt-Hopkins.

Most individuals with Pitt-Hopkins syndrome have no, or limited, speech and have no, or limited, ability to walk making them markedly different from most individuals with 18q- whose deletion does not include the TCF4 gene.

A recently published paper highlighted a potentially lethal complication for individuals with Pitt-Hopkins syndrome. The paper reported on two women in their 20’s with Pitt-Hopkins who reportedly died from gastrointestinal complications. Both women had chronic issues with constipation and severe abdominal bloating. They were aggressively managed for both conditions with oral laxatives. One woman had daily antegrade enemas through a tube placed through the abdominal wall and into the colon which was flushed daily. This procedure also allowed deflation of the colon thereby reducing her abdominal bloating. In both cases, the bloating was thought to be due to abnormal swallowing of air.

The fatal turn of events began with abdominal bloating that could not be resolved. Though both women were nonverbal, they were thought to be in pain which led to the medical consultation. Imaging studies were consistent with a malrotation of the bowel. Malrotation is a twist in the bowel that cuts off the blood flow to that section of the gut and obstructs movement of bowel contents. The lack of blood flow leads to the death of the affected bowel segment, and if not corrected quickly, it can also lead to bowel rupture, overwhelming sepsis, rapid blood loss and death. Emergency surgery was offered and declined by the families. Autopsies were declined thereby preventing a more detailed analysis and diagnosis which would have been helpful to future families with children with Pitt-Hopkins syndrome.

Even with this lack of conclusive insight into the cause of death, these cases highlight the need for awareness of this potential problem for people with Pitt-Hopkins syndrome.