Until an ultrasound scan at 20 weeks, Samantha Anderson’s second pregnancy had been going according to plan. That scan revealed that her baby had some excess fluid in their skull. The physician wasn’t too concerned, but he asked Anderson and her husband Mike, who live in Merced, California, to come in for another ultrasound in the third trimester, just to be safe.
It was at that next appointment that Mike Anderson remembers getting worried. “The ultrasound tech started getting quieter and quieter as she measured and remeasured,” he says. The physician couldn’t make an official diagnosis, but she suspected that Anderson’s baby might have a type of dwarfism. Mike remembers feeling overwhelmed by the uncertainty. He and Samantha had discussed so many what-ifs. This was not one of them.
After the baby, named Liberty, was born, physicians took a sample of umbilical cord blood and sent it for genetic testing. Liberty has achondroplasia — the most common form of dwarfism — which affects about 250,000 people worldwide. It arises from a mutation in a single gene that plays a crucial part in bone growth, and that results in an average adult height of 124–132 centimeters. Parents can pass the condition on to their children, but in most cases, the mutation arises spontaneously. Eighty percent of people with achondroplasia, like Liberty, are born to parents of average height.
The treatments have been controversial. Their approvals hinge on the drugs’ ability to make children grow taller, and faster. And although a few extra centimeters might make it easier for people with dwarfism to manage in a world built for taller people, “height is not a medical problem”, says Andrea, a genetic counselor at the Skeletal Dysplasia Program at NC Health in Wilmington, Delaware, who works with people who have achondroplasia and has the condition herself.
Many dwarfism advocates and families of children with achondroplasia are eager to know whether the drugs improve health by addressing the complications that can accompany the disorder and are sometimes life-threatening. These include sleep apnea, ear infections, pinched spinal cords, and the build-up of fluid in the skull. Answering that question, however, could take years, or even decades.
In the meantime, many people around the world are clamoring for access to the new treatments. Disability advocates worry that parents of average height, such as the Anderson's, will make a treatment decision out of fear, without understanding what it means to live with achondroplasia. Liberty, who is 4 years old and shorter than her 18-month-old sister, could be eligible to begin Voxzogo as early as October, when the FDA might allow younger children to take it. “For an average-height parent, this may be the first person with dwarfism they’ve ever known — their own kid,” says Kara Ayers, associate director of the University of Cincinnati Center for Excellence in Developmental Disabilities in Ohio, who has a form of dwarfism called oogenesis imperfect.
Parents are left with a tough choice that they must make on behalf of their children, and on the basis of incomplete data. “It’s more nuanced, I think, than a lot of people realize,” Ayers says.
Open tap
Dwarfism is a catch-all term for short stature caused by one of more than 300 genetic conditions. Scientists uncovered the genetic cause of achondroplasia in 1994. In nearly all cases, it is the same variant, a single nucleotide substitution in the gene that encodes a protein called fibroblast growth factor receptor 3 (FGFR3).
FGFR3 restricts the growth of many bones. When functioning normally, it binds to proteins called growth factors and curbs the proliferation and differentiation of chondrocytes, cells that accumulate near the ends of bones and create cartilage that eventually gets replaced by bone. The variant that causes achondroplasia keeps the receptor active most of the time. Ravi Savarirayan, a clinical geneticist and researcher at Murdoch Children’s Research Institute in Melbourne, Australia, likes to use the analogy of a garden hose. “It’s like a tap being left on,” he says — it floods the garden and hampers growth.
The most apparent effect of this overactive tap is on height. But there are other features. People with achondroplasia tend to have large heads with prominent foreheads. The condition also causes disproportionately short arms and legs, because the long bones in the limbs are where the growth differences are most marked.
Achondroplasia also comes with many potential medical challenges. One of the most serious involves the opening at the base of the skull, called the foramen magnum. In young children with achondroplasia, this hole tends to be smaller than average. That creates a pinch point at which the brain stem and spinal cord might start to get squeezed. It can be fatal, says Janet Leger, a skeletal dysplasia expert at the Waksman Center at the University of Wisconsin–Madison. Without screening, the risk of sudden death in children under the age of 5 with achondroplasia can be almost 50 times greater than it is for the general population.
About 20% of children with achondroplasia require surgery for this condition, which involves removing a portion of the skull and shaving off the bone to widen the opening. These takes pressure off the brain stem and spinal cord.
Jade and Chris found out that their son Archie needed this surgery in May 2022, when he was six months old. He didn’t have any symptoms, but a magnetic resonance imaging scan revealed that the opening was already so narrow that spinal fluid wasn’t flowing as expected. Jade remembers reading the surgical consent form and bursting into tears when she saw the dangers involved. “It’s either the operation, or you risk his life,” she remembers the neurosurgeon saying.
For Archie, the surgery was a success. But there is a chance he will need to have the opening enlarged again, as happens in 10% of children with achondroplasia who have this surgery. Or surgeons might have to operate on another pinch point lower down his back.
There are other health issues, too. FGFR3’s effects on cartilage tend to flatten the nasal bridge. Less space behind the nose and mouth increases the risk of sleep apnea, breathing problems, and ear infections. Children with achondroplasia can also have poor muscle tone, which means that it typically takes them longer than average to hit developmental milestones such as standing and walking. Archie started walking at 19 months old.
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