This case report focuses on a 4-year-old boy who showed typical signs of Coffin-Siris syndrome. CSS is a rare developmental disorder often called “fifth-digit syndrome” because it frequently causes children to have underdeveloped or missing fingernails or toenails, particularly on their pinky fingers or toes. Children with CSS also usually have distinct facial features (like thick eyebrows and long eyelashes), excess body hair, shorter height, and developmental delays.
Through advanced genetic testing, doctors discovered that the boy had a specific mutation in a gene called ARID1A, which caused his CSS.
What made this case unique—and why the doctors wrote the paper—is that the boy also developed two health conditions that aren’t usually a standard part of CSS:
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An Underactive Thyroid (Subclinical Hypothyroidism): His body wasn’t producing quite enough thyroid hormone, which is crucial for energy and growth.
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High Cholesterol (Dyslipidemia): His blood lipid (fat) levels were unusually high.
When the doctors ran more genetic tests to figure out why his cholesterol was so high, they found a second, completely separate genetic mutation in a gene called LDLR. This second mutation causes Familial Hypercholesterolemia, an inherited condition that makes it hard for the body to clear “bad” cholesterol from the blood. Having two distinct, rare genetic conditions like this is known as a “dual molecular diagnosis.”
The medical team successfully treated his underactive thyroid with a standard hormone medication (levothyroxine) and managed his high cholesterol with diet and lifestyle changes. Initially, his growth caught up nicely, but it eventually slowed down again.
Testing confirmed that the boy also had a Growth Hormone Deficiency (his body wasn’t making enough hormone to help him grow taller). This created a difficult dilemma for the doctors:
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Normally, they would prescribe growth hormone injections to help him grow.
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However, because his specific type of CSS involves the ARID1A gene—which normally acts as a “tumor suppressor” to protect the body against cancer—the doctors were highly cautious. A mutation in this gene is known to carry a higher risk for a rare type of childhood liver cancer (hepatoblastoma).
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Because there isn’t enough medical data yet to prove that giving growth hormone is completely safe for a child with this specific genetic mutation, the doctors had to carefully weigh the risks before proceeding.
The authors published this case to remind other pediatricians that children with Coffin-Siris syndrome might need extra medical screening. Even if thyroid problems and high cholesterol aren’t standard symptoms of the syndrome, doctors should proactively test for them if a child isn’t growing well. It also highlights how advanced genetic testing can unearth overlapping conditions, helping doctors tailor very specific, individualized care for a child.