Variants in the ATP1A3 Gene Mutations within Severe Apnea Starting in Early Infancy: An Observational Study of Two Cases with a Possible Relation to Epileptic Activity

Niklas Holze; Andreas van Baalen; Ulrich Stephani; Ingo Helbig; Hiltrud Muhle

doi:10.1055/s-0038-1653978

Neuropediatrics, Inhaltsverzeichnis

Neuropediatrics 2018; 49(05): 342-346
DOI: 10.1055/s-0038-1653978

Short Communication

Georg Thieme Verlag KG Stuttgart · New York

Variants in the ATP1A3 Gene Mutations within Severe Apnea Starting in Early Infancy: An Observational Study of Two Cases with a Possible Relation to Epileptic Activity

Niklas Holze

¹Department of Neuropediatrics, University Medical Center Schleswig Holstein, Kiel, Germany

,

Andreas van Baalen

¹Department of Neuropediatrics, University Medical Center Schleswig Holstein, Kiel, Germany

,

Ulrich Stephani

¹Department of Neuropediatrics, University Medical Center Schleswig Holstein, Kiel, Germany

,

Ingo Helbig

¹Department of Neuropediatrics, University Medical Center Schleswig Holstein, Kiel, Germany

²Division of Neurology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States

,

Hiltrud Muhle

¹Department of Neuropediatrics, University Medical Center Schleswig Holstein, Kiel, Germany

› Institutsangaben

Abstract

Mutations in the ATP1A3 gene are known to cause alternating hemiplegia of childhood (AHC) and rapid-onset dystonia parkinsonism (RDP). Both conditions are childhood-onset neurological disorders with distinct symptoms and different times of onset. ATP1A3 has also been associated with CAPOS syndrome (cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss). Within the various ATP1A3-related neurological syndromes, a specific genotype–phenotype correlation is starting to emerge. Several mutations such as the relatively common p.E815K pathogenic variant have been shown to strongly correlate with AHC, while others may cause both AHC and RDP. A significant subset of patients with AHC and RDP are reported to have epileptic seizures. Even though detailed clinical descriptions of seizures in childhood are rare, seizures involving apneic events seem to be frequent in ATP1A3-related neurological disorders. Here, we describe two children with unexplained severe apnea beginning around the first year of life and pathogenic variants in ATP1A3. We hypothesize that the symptoms are early-onset autonomic seizures related to the underlying pathogenic ATP1A3 variants.

Keywords

apnea - epilepsy genetics - autonomic seizures - developmental delay

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Referenzen

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