A case report in Frontiers in Genetics highlights that Coffin-Siris syndrome type 4 can present with atypical features, emphasizing the importance of expanded genetic testing and personalised care strategies.
A new case report in Frontiers in Genetics adds to evidence that Coffin-Siris syndrome type 4 can look far less typical than doctors may expect. The study centres on a 3-year-old girl in China who had significant language delay, broader developmental problems and autistic traits, yet did not have the classic fifth-finger abnormalities often linked with Coffin-Siris syndrome. Whole-exome sequencing found a previously unreported de novo frameshift duplication in SMARCA4, the gene behind this form of the condition, and the authors classified it as pathogenic.
The report places the child within a wider pattern of clinical variation that has become increasingly clear in recent years. Review data cited by the authors found 40 genetically confirmed SMARCA4-related cases, including the new patient, and showed that intellectual disability was present in every case, while autistic features appeared in 42.5%. Fifth-digit hypoplasia, long treated as a hallmark sign, was seen in only 55% of patients. GeneReviews and MedlinePlus both note that Coffin-Siris syndrome is genetically diverse and that SMARCA4 is one of several genes that can cause it, with presentation varying widely from one child to another.
The girl’s exam also showed some features that fit the syndrome and others that did not. She had thick eyebrows, long eyelashes and a flat nasal bridge, along with low growth measurements and delayed development, but her hands and feet were normal. Brain imaging showed thinning of the corpus callosum, an area that connects the two sides of the brain, while her eye examination found no structural abnormality. That matters because prior reports have linked SMARCA4 variants not only with developmental delay and autism but also with eye malformations in some patients, including those with loss-of-function variants.
The authors argue that the case strengthens the case for broader genetic testing in children with developmental delay, autism and distinctive facial features, even when the expected limb findings are absent. They also note that truncating SMARCA4 variants may carry tumour-related risk, although the true level of risk remains uncertain and formal surveillance guidance is still lacking. In the meantime, they say families should receive balanced counselling and care should be tailored to the child rather than to a single textbook description of Coffin-Siris syndrome.
Disclaimer: This content is for informational purposes only and is not intended to be a substitute for professional medical judgment, advice, diagnosis, or treatment.
