Cleidocranial dysplasia

In the Netflix series “Stranger Things”, the character Dustin’s missing a few teeth, and he says [“I’ve told you a million times!

My teeth are coming in! It’s called cleidocranial dysplasia!”], he’s then asked to [“do the arm thing...CRACK—GROANS”].

Both Dustin and his real-life counterpart—Gaten Matarazzo—have a rare genetic condition—cleidocranial dysplasia or sometimes cleidocranial dysostosis.

“Cleido-” means “clavicle”, which is the collarbone, and “-cranial” refers to the skull, “dys-” means abnormal, and “-plasia” means formation.

So people with cleidocranial dysplasia usually have underdeveloped or missing collarbones, which gives them a wide range of shoulder movement, as well as abnormalities in other bones, especially the skull bones including the jaw, which can result in delayed eruption of the teeth.

Now cleidocranial dysplasia, or CCD, is a rare congenital disorder—meaning present since birth—and it’s caused by a mutation in a gene on chromosome 6, located at 6p21, which means chromosome 6, the short arm, or P, region 2, band 1.

The gene’s called CBFA1 or RUNX2, so let’s just go with RUNX2. RUNX2 mutations are inherited in an autosomal dominant pattern, meaning if one parent has the disorder and one doesn’t, 50% of their offspring will inherit the disorder and 50% won’t.

Those that inherit the disorder end up with one chromosome that has the mutation and one normal chromosome in every cell, and having just one chromosome with the mutation is enough to cause the disorder.

Sometimes, though, the mutation might be sporadic, meaning it wasn’t inherited from the parents, but it’s a new mutation that just pops up in one of the children.

This RUNX2 gene encodes for a specific RUNX2 protein that acts as a transcription factor. Transcription factors help control the activity of other genes, and it’s thought that RUNX2 helps regulate genes involved in the differentiation of stem cells into osteoblasts, or bone-forming cells, as well as potentially chondrocytes, cells that help form cartilage.

With CCD, if even one chromosome in each cell has a mutation in the RUNX2 gene, fewer functional RUNX2 protein will be produced overall, meaning fewer functional osteoblasts and chondrocytes will be produced, and so there’ll end up being delayed ossification, or delayed formation of bone.

In about a third of the cases of CCD, there doesn’t seem to be any mutation in the RUNX2 gene; meaning that there’s probably some other mechanism that’s involved.

In any case, as a result of these bone-forming cell abnormalities, people with cleidocranial dysplasia often have either underdeveloped or missing clavicles—or collarbones—which can give them increased range of shoulder movement.

CCD’s also commonly characterized by delayed or failed closure of the fontanelles, or soft spots in the skull. Other features might include supernumerary teeth, which are extra teeth that might appear in addition to regular 32 teeth in the adult mouth, failure to shed the primary or baby teeth, as well as failed eruption of permanent teeth.

Also, a shorter stature and a number of other bone abnormalities have been observed in some people with CCD. As far as treatment goes, since it’s a genetic mutation there’s no cure for cleidocranial dysplasia, although someone with CCD might benefit from surgical correction depending on the bone abnormality.

Alright, as a quick recap, cleidocranial dysplasia or dysostosis is an autosomal dominant disorder that usually involves the RUNX2 gene, which helps control the differentiation of osteoblasts, which results in abnormal formation of various bone structures like the clavicle, the fontanelles, and the teeth.

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