Same Gene, Different Journeys : Four Faces of Coffin-Siris Syndrome
Contributors
- 1. Department of Pediatrics, Child Development Centre, Pushpagiri Institute of Medical Sciences and Research Centre, Thiruvalla, Kerala, India
Description
Background: Coffin–Siris syndrome (CSS) is a rare neurodevelopmental
disorder caused by pathogenic variants in genes of the BAF chromatinremodelling
complex, most commonly ARID1B. It is characterized by
developmental delay, dysmorphic features, seizures, feeding difficulties,
and variable fifth-digit anomalies. Marked phenotypic heterogeneity often
leads to delayed recognition, particularly in resource-limited settings.
Methods: We report a case series of four genetically confirmed children with
6q25.3–q27 deletions involving ARID1B, evaluated at a tertiary care centre. Clinical,
neurological, radiological, audiological, and molecular findings were analyzed.
Results: All four children presented in infancy with global developmental delay,
recurrent seizures, and significant feeding difficulties requiring nutritional
support. Dysmorphic facial features were present in all cases; however, classical
fifth-digit hypoplasia was observed in only one child. Neuroimaging revealed
structural brain abnormalities in all patients, including corpus callosum
thinning, cerebellar vermis hypoplasia, hydrocephalus, and periventricular
leukomalacia. Electroencephalography showed generalized background
slowing in each case. Hearing impairment was identified in three children.
Muscle tone varied, with hypotonia in three cases and hypertonia in one,
highlighting phenotypic diversity despite a shared molecular basis. Wholeexome
sequencing confirmed de novo deletions involving ARID1B in all patients.
Conclusion: This case series underscores the broad clinical spectrum of
ARID1B-related CSS and demonstrates significant genotype–phenotype
variability even among patients with similar chromosomal deletions. Limb
anomalies may be absent, and neurological manifestations predominate.
Early genetic evaluation in infants with unexplained developmental delay
and dysmorphism facilitates timely diagnosis, multidisciplinary management,
and genetic counselling. Increased awareness and integration of molecular
testing are essential to improve recognition of CSS in developing countries.
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Additional details
Dates
- Accepted
-
2026-05-31
References
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