What you should know about Rett syndrome, the condition that Richard Engel's son had

Richard Engel, chief foreign correspondent for NBC News, announced on Thursday that his 6-year-old son Henry, diagnosed with Rett syndrome as an infant, had died.

In a tweet posted on Aug. 18, Engel wrote: "Our beloved son Henry passed away. He had the softest blue eyes, an easy smile and a contagious giggle. We always surrounded him with love and he returned it, and so much more. "

Engel's tweet included a link to a page on the Texas Children's Hospital site, which explained Henry's medical journey and how he was diagnosed with Rett syndrome. The disorder is incredibly rare — particularly so for boys, said Dr. Tim Benke, a professor in pediatric neurology at the University of Colorado.

"It happens in about 1 in 20,000 to 1 in 10,000 female births. But it's so rare we don't know how often it happens in male births," Benke told NPR.

What is Rett syndrome?

Rett syndrome, as defined by the International Rett Syndrome Foundation, is a rare genetic neurological disorder that begins to show up between 6 and 18 months of age. Children start to miss developmental milestones or lose skills they'd once had.

A diagnosis is based on an array of factors, including difficulties with movement, the loss of hand and language abilities, and constant hand motions, "such as hand-wringing, squeezing, clapping or tapping, putting hands in the mouth, or washing and rubbing movements," according to the Mayo Clinic. These symptoms trigger clinicians to order specific testing to clarify the diagnosis by searching for a genetic misspelling in the MECP2 gene.

What do we know about the development of Rett syndrome?

The disorder occurs very rarely in males, and is typically more severe than with females. Many begin experiencing symptoms at or shortly after birth, with significant problems occurring very soon after. These patients require aggressive medical intervention.

"There's a lot that we don't fully understand yet," says Benke. "There is a discrepancy between male and female births, and we have some theories as to why. And we think that the answer is that the genetic misspelling happens around the time the egg and sperm come together. And it's more likely to happen in sperm than it is in eggs. It's so rare that we don't know how often it happens."

This has created a challenge for the medical community: Due to the rarity of this condition in males, it's difficult to find enough of them to participate in clinical trials for treatments.

While Rett syndrome may not be well-known among the general public, the foundation said that it is in the forefront of research happening across the globe.

Is there a cure for Rett syndrome?

"At the moment there is no cure for it," Benke told NPR. "It's a genetic disorder, you can't go back and fix that misspelling [in the genes]."

"All the treatments are systemic," he added. "You try and treat seizures, and you're trying to improve things like muscle tone, which in the case of Henry Engel was the most problematic for him."

At the moment, antiseizure drugs like oxcarbamazepine can be prescribed to help control seizures, and sedatives like clonidine can help reduce pain. Benke is hopeful that new therapies that are coming along will be beneficial to those with Rett syndrome, males and females.

A drug to treat symptoms of Rett syndrome in women completed phase three trials, he said. The drug, trofinetide, has been submitted to the FDA for approval, and researchers are hoping to hear back in 2023. If approved, there is a chance that this therapy could apply to males as well, Benke said.

"It's not a home run, but it's a therapy that's going to get us on first base that we think could be really helpful," he added.

Benke emphasized that there are support systems for people with Rett syndrome and their families. Local and national associations, such as the Rocky Mountain Rett Association and the International Rett Syndrome Foundation, are dedicated to connecting people with specialized care, he said. "It's important for people to know that it sounds hopeless, but there's hope there."

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