The study reports on two siblings—a 10-year-old child and a 2-year-old child—who presented with unexplained developmental delays and physical features present since birth. Through genetic testing, researchers pinpointed the specific DNA variations causing their conditions.
Key Findings & Results
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Both Siblings Have Coffin–Siris Syndrome (CSS) resulting via a change in the SMARCB1 gene.
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Coffin–Siris syndrome is a rare genetic disorder characterized by overall developmental and speech delays, distinct physical or facial features, and underdeveloped or missing pinky fingernails or toenails.
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The Older Sibling Has a Second Rare Condition (Sialuria):
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The 10-year-old patient carries an additional mutation in the GNE gene, which causes autosomal dominant sialuria—an extremely rare metabolic error that causes excess free sialic acid to build up in the body.
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This was missing in the younger sibling, making the 10-year-old the first reported case of an individual having both Coffin–Siris syndrome and Sialuria simultaneously.
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Clinical Impact:
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The older sibling, who carries both genetic mutations, exhibited more severe cognitive and developmental impairments compared to the younger sibling, who only carries the SMARCB1 variant.
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Tests indicated moderate social and developmental delays, along with attention-deficit symptoms, but ruled out Autism Spectrum Disorder (ASD).
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By using advanced genomic testing, doctors were able to give the family an accurate diagnosis for previously unexplained childhood developmental challenges. The case highlights how multiple rare genetic variations can coexist in one person, compounding developmental delays and helping doctors better understand how different gene mutations interact.