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World J Clin Cases. Jul 6, 2026; 14(19): 120716
Published online Jul 6, 2026. doi: 10.12998/wjcc.120716
De novo ARID1A Coffin-Siris syndrome with hypothyroidism and dyslipidemia: A case report and literature review
Kyriaki Tsiroukidou, Dimitrios G Goulis, Charalampos Antachopoulos, Panagiota Zissiadis, Ioannis Taiganidis, Parthena Savvidou, Maria G Grammatikopoulou, Ilektra Toulia, Michael N Fragos
Michael N Fragos, Ilektra Toulia, Ioannis Taiganidis, Panagiota Zissiadis, Kyriaki Tsiroukidou, Pediatric Endocrinology Unit, 3rd Department of Pediatrics, Hippokration General Hospital of Thessaloniki, Aristotle University of Thessaloniki, Thessaloniki GR-54642, Kentrikí Makedonía, Greece
Maria G Grammatikopoulou, Immunonutrition Unit, Department of Rheumatology and Clinical Immunology, Larissa University General Hospital, Medical School, Faculty of Health Sciences, University of Thessaly, Larissa GR-41223, Greece
Parthena Savvidou, Endocrine Unit, 3rd Department of Pediatric, Hippokration General Hospital, Aristotle University of Thessaloniki, Thessaloniki GR-54642, Kentrikí Makedonía, Greece
Charalampos Antachopoulos, 3rd Department of Pediatrics, Hippokration General Hospital, Aristotle University of Thessaloniki, Thessaloniki GR-54642, Kentrikí Makedonía, Greece
Dimitrios G Goulis, Unit of Reproductive Endocrinology, 1st Department of Obstetrics and Gynecology, Faculty of Health Sciences, Medical School, Aristotle University of Thessaloniki, Thessaloniki GR-54124, Greece
Co-first authors: Michael N Fragos and Ilektra Toulia.
Author contributions: Toulia I, Taiganidis I, Zissiadis P, Savvidou P, and Tsiroukidou K performed clinical assessments and examinations, contributing to data collection; Fragos MN, Toulia I, and Grammatikopoulou MG contributed to writing, reviewing and editing the manuscript; Tsiroukidou K, Grammatikopoulou MG, Antachopoulos C, and Goulis DG contributed to interpretation; Tsiroukidou K contributed to the conceptualization and methodology; Tsiroukidou K and Grammatikopoulou MG supervised the work; and all authors have read and approved the final version to be published.
AI contribution statement: No AI tool was involved in the generation of research data, interpretation of results, or formulation of conclusions.
Informed consent statement: Written informed consent was obtained from the patient and his parents for publication of this report and any accompanying images.
Conflict-of-interest statement: The authors declare that they have no conflict of interest to disclose.
CARE Checklist (2016) statement: The authors have read the CARE Checklist (2016), and the manuscript was prepared and revised according to the CARE Checklist (2016).
Corresponding author: Maria G Grammatikopoulou, PhD, Assistant Professor, Immunonutrition Unit, Department of Rheumatology and Clinical Immunology, Larissa University General Hospital, Medical School, Faculty of Health Sciences, University of Thessaly, Biopolis Cam
pus, Larissa GR-41223, Greece.
mgrammat@uth.gr
Received: March 6, 2026
Revised: May 15, 2026
Accepted: June 5, 2026
Published online: July 6, 2026
Processing time: 118 Days and 14.6 Hours
BACKGROUND
Coffin-Siris syndrome (CSS) is a rare BRG1/BRM-associated factor (BAF) - SWI/SNF (SWItch/Sucrose non-fermentable) - related neurodevelopmental disorder. Endocrine manifestations primarily involve growth disturbances, whereas thyroid dysfunction and dyslipidemia are not considered recurrent syndromic features.
CASE SUMMARY
A 4-year and 4-month-old boy with typical CSS features (coarse facies with long eyelashes, fifth-digit distal phalanx/nail hypoplasia/aplasia, dorsal hypertrichosis, developmental delay/intellectual disability) and short stature developed subclinical hypothyroidism at the age of 4 years and 2 months old, while also exhibiting hypercholesterolemia. Whole-exome sequencing identified a pathogenic ARID1A variant (c.4102-1G>A) consistent with CSS and a heterozygous likely pathogenic LDLR variant (c.251C>T), consistent with familial hypercholesterolemia. Levothyroxine treatment achieved biochemical euthyroidism, and along with lifestyle interventions, was followed by transient improvement in growth velocity. Dyslipidemia was managed conservatively. Subsequent decline in growth velocity and low insulin-like growth factor 1 concentrations prompted growth hormone (GH) stimulation testing, which proved to be pathological. Consideration of recombinant GH therapy raised concerns due to the reported increased hepatoblastoma risk in ARID1A-related CSS and insufficient clinical evidence and recommendations.
CONCLUSION
Although not typical for CSS, this proband highlights that thyroid and lipid abnormalities may coexist, and supports selective thyroid-stimulating hormone/free T4 (thyroxine) and lipid screening in CSS when clinically indicated, while attributing hypercholesterolemia primarily to LDLR-mediated familial hypercholesterolemia. Individualized endocrine surveillance and follow-up are essential for the optimal management of CSS in children.
Core Tip: Coffin-Siris syndrome (CSS) is a rare neurodevelopmental disorder involving the BRG1/BRM-associated factor (SWI/SNF) chromatin-remodeling complex, characterized by coarse facial features, distal phalanx hypoplasia/aplasia, developmental delay, and multisystem involvement. We report a child with CSS, subclinical hypothyroidism, and familial hypercholesterolemia caused by a heterozygous LDLR variant. Lifestyle changes and levothyroxine initially improved growth (7.6 cm/year), but growth velocity subsequently declined (4.2 cm/year) in parallel to insulin-like growth factor 1 levels. A glucagon stimulation test confirmed growth hormone (GH) deficiency. Recombinant GH therapy in ARID1A-related CSS should be individualized because impaired tumor suppression and possible hepatocyte damage may increase hepatoblastoma risk.
