What is Rett syndrome, the disease that took the life of NBC's Richard Engel's 6-year-old son Henry

NBC News Chief Foreign Correspondent Richard Engel announced on Thursday that his 6-year-old son, Henry, passed away after a long battle with Rett syndrome on August 9. In his heartfelt tweet, Engel said that his son had the "softest blue eyes, an easy smile and a contagious giggle." When Henry, born in September 2015, stopped meeting his developmental milestones as an infant, a genetic test revealed that he had something severe. "It’s life long, not treatable,” Engel had said about his son's diagnosis in a 2018 interview with TODAY adding, “It was the worst day of my life." 

After his parents discovered that Henry had Rett syndrome, he was brought to Texas Children's Hospital's Duncan Neurological Research Institute (Duncan NRI) in 2018. Dr. Huda Zoghbi, director of the Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital, worked with the Engel family during Henry's treatment.  

According to the National Institute of Neurological Disorders and Stroke, Rett syndrome "is characterized by normal early growth and development followed by a slowing of development, loss of purposeful use of the hands, distinctive hand movements, slowed brain and head growth, problems with walking, seizures, and intellectual disability." It is a unique genetic disorder caused by the MECP2 gene on the X chromosome not functioning perfectly due to a mutation on the gene in most cases.

Moreover, the condition "affects girls almost exclusively." According to Zoghbi, who discovered that MECP2 mutations cause Rett syndrome, Henry was the first person to have Rett syndrome of a particular kind. Zoghbi said, “We’ve learned so much from so many patients with Rett syndrome, but because (Henry’s) mutation was a little different, it allowed us to think slightly differently about other approaches.” 

"It’s more common in females because they have two X chromosomes; when it occurs in males, it’s more severe because they only have one X chromosome. That's because the non-affected X chromosome in females allows half their cells to have a normal copy of the MECP2 gene, whereas in males, all their cells are affected due to the mutation," Dr. Marc Patterson, a pediatric neurologist at the Mayo Clinic in Rochester, Minnesota, told TODAY.

“One of the earliest signs in a typical case is the growth of the head slows down, and that (is) classically seen before there’s any change in development,” said Patterson, asking parents of infants to ensure that at checkups their baby's head is measured regularly. He further explained that developing unusual movements of the hands "described as hand wringing, or hand knitting" is another characteristic of the condition. "Patients may also experience dystonia, where muscles contract involuntarily and the limbs or trunk are held stiffly in an unusual position," he added.

"Children who are able to acquire speech tend to lose that ... and there's quite a high frequency of autistic features," Patterson said. "Additionally, a number of children will get an unusual pattern of breathing and other problems, including heart rhythm problems."

“It’s not uncommon for boys ... to succumb to this illness within the first decade,” Patterson added. According to Dr. Sumit Parikh, a neurologist with the Center of Pediatric Neurosciences at the Cleveland Clinic, “The lifespan for typical Rett syndrome (in women) now is much better than it used to be, with individuals surviving into their 20s to 50s.” However, Parikh also clarified that the condition is not inherited. "It is a new change that happens in the baby's DNA right after conception. ... As far as we know, there's not a specific cause for it, and it seems to be random," he added.

Zoghbi's team of scientists is now using Henry's cells to further the research on Rett syndrome since he had a unique mutation, according to TODAY. Because Henry's mutation affected the function of the MECP2 gene in such a way that it caused an important protein for brain development to be produced at lower levels, researchers are inspired to think of ways to enhance the level of the protein made by this gene.

Remembering Henry, Zoghbi said, "Henry helped us make a very strong connection. You just can’t help it. His sweet smile, he’s so good. He just will smile and light up your day." She acknowledged the importance of the relationship between professionals and patients. "(Henry) became a driving force in the lab because the lab members met him and knew him and played with him," Zoghbi said. "This kind of relationship is very important because it reminds everybody in the lab that there are human beings at the end of the road who are waiting and may one day benefit from this work."