Based on the provided case report, here is a summary of the abstract and clinical findings for this patient with Coffin-Siris syndrome (CSS).
Overview
The report describes a 9-year-old Japanese female born as an extremely low birth weight (ELBW) infant (752 g). While her early phenotype was nonspecific and obscured by her complex neonatal course, she was eventually diagnosed with CSS through genetic analysis. This case is significant as the first detailed clinical description of a patient harboring the specific ARID1B nonsense variant (p.Trp1195Ter).
Clinical Presentation and Results
The patient’s condition evolved from nonspecific neonatal distress to a recognizable (though atypical) CSS profile:
-
Neurodevelopmental Impact: The patient experienced severe intellectual and motor developmental delays. At 9 years old, she was unable to speak meaningful words and was diagnosed with Autism Spectrum Disorder (ASD) and focal epilepsy.
-
Physical Features: As she aged, characteristic facial features emerged, including long eyelashes, bushy eyebrows, a broad nasal tip, and a large mouth.
-
Atypical Findings: Notably, she lacked the “hallmark” CSS feature of hypoplasia (underdevelopment) of the fifth fingernail and toenail. Radiographic exams also showed no abnormalities in the phalanges (finger bones).
-
Internal Anomalies: Brain MRI revealed agenesis of the corpus callosum (the absence of the structure connecting the two brain hemispheres).
Genetic Analysis
Because the clinical presentation was atypical—particularly the absence of fifth-digit nail issues—the diagnosis relied on targeted exome sequencing.
-
Mutation: A de novo (spontaneous, not inherited) heterozygous nonsense variant in the ARID1B gene was identified.
-
Significance: ARID1B is the most common gene associated with CSS, appearing in over 60% of cases. This specific variant was reclassified from “likely pathogenic” to “pathogenic” following this clinical report.
Conclusion
The authors conclude that genetic analysis is a vital tool for diagnosing CSS when clinical features are subtle or evolving, especially in infants with complex medical histories like those born with ELBW.