Variant in the ATP1A3 gene: a review of current literature and the development of CAPOS syndrome in a preterm infant – a clinical case report

• Irina V. Nikitina
• Ivan M. Amelin
• Lyubov’ V. Ushakova
• Alina A. Dokshukina
• Anna A. Lenyushkina
• Victor V. Zubkov

Abstract

The integration of modern molecular genetic methods, particularly Next-Generation Sequencing (NGS), into clinical practice has expanded diagnostic capabilities for children from the neonatal period onward. Early genetic disease detection is a promising avenue for advancing neonatology and pediatrics. It enables timely treatment selection and adjustment, prognosis determination, and genetic counseling for affected families.

Hereditary nervous system disorders often manifest in the neonatal period as convulsive syndromes mimicking perinatal complications. Their etiology is frequently diagnosed much later, delaying pathogenetic therapy initiation and contributing to early disability in affected children.

Various authors estimate the average age for diagnostics of genetically-caused nervous system developmental disorders as 3–6 years.

Pathogenic ATP1A3 mutations are the primary cause of several rare neurological disorders in infants and children with overlapping phenotypes. These include Alternating Hemiplegia of Childhood 2 (AHC2), Rapid-Onset Dystonia-Parkinsonism (DYT12 or RDP), CAPOS syndrome (Cerebellar ataxia, Areflexia, Pes cavus, Optic atrophy, and Sensorineural hearing loss), Developmental and Epileptic Encephalopathy 99 (DEE99), and Childhood-Onset Schizophrenia (COS).

The prevalence of ATP1A3-related disorders remains unclear due to rarity, diverse clinical manifestations and gradual development of characteristic symptom complexes.

Aim. This clinical observation describes a very premature infant with a variant in the ATR1A3 gene, highlighting the distinctive features and stages of the differential diagnostic search during the neonatal period. The case study focuses on the formation of geno-phenotypic correlations typical of CAPOS syndrome and the degree of their manifestation in the presented patient.

This article presents a clinical case of a severely premature infant diagnosed with an ATP1A3 gene variant. It also reviews current literature on ATP1A3 variant phenotypes, pathogenesis, clinical features, diagnostic approaches and rehabilitation potential.

Keywords: premature newborn; CAPOS syndrome; ATP1A3 gene; mutation; whole exome sequencing; congenital cataract; hearing loss

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