What is Schaaf-Yang Syndrome?
Where to start with this one. Well, Schaaf-Yang Syndrome (SYS) is an “ultra-rare” genetic disorder caused by a mutation on the MAGEL2 gene on chromosome 15. It’s named after the doctors that discovered the unique mutation, Dr Christian Schaaf and Dr Yaping Yang of Baylor Medical College in 2013. Currently there are at least 250 people diagnosed with Schaaf-Yang Syndrome in the world. Yes, in the world. Clinically, it can look a lot like Prader-Willi syndrome as there are some overlaps and Prader-Willi syndrome is also caused by several mutations on chromosome 15.
How do you get Schaaf-Yang Syndrome?
Well, you’re born with it. The magic happens while your dna is building your tiny little body. And you can develop it one of two ways: either genetically passed down from your father or through a random mutation.
Genetically, you get one copy of each chromosome from your mother and one copy from your father. Then your dna building blocks decide which copy gets “turned on”…kind of like a series of light switches. Schaaf-Yang Syndrome can happen when the father’s chromosome carries it. On the Magel2 gene, the chromosomes that are “turned on” come from the father’s side. So the father’s copy of that chromosome is flipped up (on) and the mother’s copy is flipped down (off). You can have a perfectly normal one from your mother but this particular chromosome is paternal. If the mother’s chromosome carries it, it can be passed on but won’t be turned on in that generation. For example, if a mom has the chromosome and passes it to a son, he won’t have the mutation (because he gets a perfect copy from his dad that is turned on) but will still have it stored in his DNA. He can then pass it to his children who would then have the mutation. If the mom passes it to a daughter, it won’t show up again until there’s a son born down the line that then has a child because it’s on the paternal (male) side of the DNA.
With a random mutation, anyone can develop it. (This is how Charlie’s body developed it.) Every human has AT LEAST 100 random mutations to their DNA. It’s what makes every one of us unique. It’s also why you can have a child with red hair born to parents with black hair. Or a lefty born into a family of righties. For Charlie, instead of getting red hair or coming out left handed, he developed a Magel2 gene mutation on chromosome 15 as one of his 100+ mutations. (He really IS a mutant! And a darn cute one!)
What are the symptoms?
Well first off, the spectrum of SYS symptoms is really wide. Some have been diagnosed with it and they only have high functioning autism. Others, like Charlie, have many different systems affected. It depends which part of the gene is mutated and which proteins/amino acids are affected.
At birth, there are some physical symptoms you may notice. Charlie had joint contractions in his fingers, an inability to suck, an inability to swallow food (he was protecting his airway), high muscle tone in his arms and legs, low muscle tone in his body core, undescended testicles, and micropenis. As he grew it became clear he was also developmentally, intellectually, and physically challenged.
What does SYS look like on Charlie?
90% of SYS people have autism. Charlie is no exception. In addition, he also has the mentality of about a 4 month old. He can’t really take direction and we don’t know if he understands a whole lot.
He has a very high pain threshold. In fact, he’s had three femur breaks during diaper changes due to osteoporosis in his bones and he never cried. He’s had double hip surgery. No crying. He gets IV’s during multiple hospital stays for gastric issues (Mallory tears causing internal bleeding) or respiratory issues (pneumonia and collapsed left lung) and no crying. It’s not that he’s never cried. He has. We THINK he cries when he has really really bad gas bubbles. So it’s very far and few between, thankfully. But he never cries due to hunger, thirst, being wet, being cold or hot, being uncomfortable, or from what most people would consider something painful like a dislocated thumb, a burn on his leg from a cord, hip surgery, or a broken femur.
Charlie has a laryngeal cleft, he aspirates 50% of the time as he swallows, has lazy eye, delayed gag reflex, delayed safety reflexes (so he doesn’t stop himself from falling over), joint contractures, and a feeding tube. Of all the issues he faces, the kyphosis is probably the most devastating. Kyphosis is hunchback. Charlie’s rib cage is rotating to the right and has caused his right rib cage to deform considerably. That causes pressure on the lungs, in particular the left lung. But Charlie is strong. He is so super strong. He defies his doctors’ expectations all the time.
What does the future hold for Charlie and people like him?
This syndrome doesn’t come with a map. We don’t know the path forward. The oldest person with Schaaf-Yang Syndrome is 37 years old. Most of the babies or fetuses with SYS pass away before being born…or right afterwards. Charlie’s path is a little more written out due to the kyphosis. It’s not expected that he will make it to middle age. We’re hoping he makes it to adult.
Is there a cure?
This is a trick question, right? No, there isn’t a cure. And because there is a very, very small number of people who have been diagnosed, there isn’t a whole lot of research going on to find one. Dr Schaaf does continue to seek answers and they’ve managed to learn more about genes themselves just researching the link between SYS and Prader-Willi Syndrome.
There is some research into whether oxytocin (yes, the love hormone) can “rescue” some of the symptoms of SYS…as well as Prader-Willi and autism. Most of the research has been on mice and is very promising. Charlie DID try intranasal (nasal spray) of oxytocin when he was about 20 months old. It DID rescue some social cues. He started looking around and his eyes could focus. (Before they would bounce if he tried turning his head) He started looking at faces and doing some mimicking. He started anticipating. For example, being tickled. We did the same gesture to him every time before we tickled him and he started remembering when we did that gesture, he was going to get tickled. Then he’d either pull both of his arms in to cover his body or try to keep our hands away. Smiles came later, much later, but they did eventually come.
Is there somewhere I can go to read more about Schaaf-Yang Syndrome and the research?
My friend, Google is a thing…..I’m just kidding. I’m being sarcastic is more like it. But yes, yes, yes there is. And I’m more than happy to throw you a few links.
First up is Foundation for Prader-Willi Research. Because SYS and Prader-Willi are “sister” disorders, the Prader-Willi foundation has kindly provided some information about the crossovers and SYS alone.
Next is the National Institutes of Health most recent oxytocin/Magel2/autism studies. They’re getting closeerrrrrr. Yay!
Here’s an early research paper on oxytocin rescuing social interactions in mice affected with Magel2 disruptions before Magel2 was named Schaaf-Yang Syndrome. It’s from the Oxford Journal in 2010.
A great research paper describing the impact SYS has had on the people diagnosed with it and their families/caregivers.
Let’s not forget the hard workers and “out of the box” thinkers who are putting a name to this very rare disorder- Dr Christian Schaaf and Dr Yaping Yang. (Scroll all the way down. She’s at the bottom.)
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