Polymorphism of clinical manifestations of orphan diseases in children with ARID1A and ARID1B gene mutations





neurodevelopmental disorders, epilepsy, genetic syndrome, Coffin-Siris syndrome, ARID-dependent disorders, subependymal giant cell astrocytoma


The Department of Psychoneurology for Children with Perinatal Pathology and Orphan Diseases at the SI “Institute of Pediatrics, Obstetrics and Gynecology named after academician O.M. Lukyanova of the NAMS of Ukraine” has a multidisciplinary team which provides care to children with orphan diseases from all over Ukraine. Thanks to modern methods of clinical, instrumental and genetic diagnostics, it is possible to establish a definitive diagnosis.

Aim - to provide a literature review and a clinical case of a child with pathogenic variants of the ARID family genes, which, in particular, lead to the development of Coffin-Circe syndrome (CCS), autism spectrum disorder and intellectual disability, as well as the development of nervous system tumors in children.

The article presents a clinical case of a child with a rare disease - CCS, which is part of the ARID gene mutation spectrum. The general clinical and neurological examination, electroencephalographic sleep monitoring, magnetic resonance imaging, whole-exome sequencing, and pathological examination were performed. The difficulty of diagnosis was that a child with skin manifestations of phacomatosis was diagnosed with subependymal giant cell astrocytoma (SGСA) by magnetic resonance imaging, but there were no mutations characteristic of tuberous sclerosis (TSC1, TSC2). Pathologically, the patient was confirmed to have grade I SGСA according to the World Health Organization classification. Two pathogenic mutations of the ARID1A gene in the compound heterozygous state were detected by whole-exome sequencing. After combining the combined clinical and instrumental signs, the diagnosis of CCS with grade I SGСA was established.

Conclusions. The disorders caused by ARID1A and ARID1B mutations belong to a spectrum that includes syndromic and non-syndromic cases of intellectual disability, autism spectrum disorder, and CCS with or without a variety of somatic and neurological symptoms, and are grouped under the general term “ARID-related disorders”. Only a thorough medical history, clinical examination, and modern methods of instrumental and genetic diagnostics can make a diagnosis.

The research was carried out in accordance with the principles of the Declaration of Helsinki. Informed consent of the women was obtained for the research.

No conflict of interests was declared by the authors.


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