Fever-related ataxia: a case report of CAPOS syndrome

Abstract

Background CAPOS ( C erebellar ataxia, A reflexia, P es cavus, O ptic atrophy and S ensorineural hearing loss) syndrome is caused by the heterozygous mutation, c.2452G > A, in the ATP1A3 gene. Other mutations in this gene can cause a spectrum of overlapping phenotypes including alternating hemiplegia of childhood, rapid onset dystonia parkinsonism, early infantile epileptic encephalopathy and fever induced paroxysmal weakness and encephalopathy. The phenotype is still mistaken for mitochondrial/metabolic disorders and follow up studies are scare. Case presentation We report a 20 year old Norwegian male with ataxia, sensorineural deafness and visual loss. Before the age of five he experienced three fever related episodes of acute neurological deterioration when he temporarily lost his acquired motor skills and developed persistent gait and limb ataxia. In childhood, he developed bilateral optic atrophy and bilateral sensorineural hearing loss. Motor skills improved and at age 20 the patient showed a mild ataxia, hearing loss and reduced vision. A c.2452G > A mutation in the ATP1A3 gene was identified and CAPOS syndrome was confirmed. Conclusions This is the first Norwegian patient reported with CAPOS syndrome. Our patient had a de novo , previously identified ATP1A3 mutation. The combination of recurrent episodes of fever related ataxia, loss of motor skills in early childhood, and early onset hearing and vision loss is typical of CAPOS syndrome. Previous reports suggest a gradual progression of the disease after the initial episodes, while this patient showed a good outcome with improvement of motor skills from adolescence long after the last deterioration episode. Electronic supplementary material The online version of this article (10.1186/s40673-019-0096-3) contains supplementary material, which is available to authorized users.

CAPOS Syndrome with Fluctuating Symptoms

“…3 18 Animal studies have demonstrated that increased temperature leads to more leakage of Na + /K+ ions through the Na + /K + ATPase, providing a possible mechanism for febrile illness triggering CAPOS episodes. 19 Consistent with this mechanism, the patient's spells were easily triggered by overheating either from ambient temperature elevations or from fevers.…”

Genetically altered animal models forATP1A3-related disorders

“…AHC, alternating hemiplegia of childhood; ASD, autism spectrum disorder; CAPOS, cerebellar ataxia, areflexia, pes cavus, optic atrophy and sensorineural hearing loss; COS, childhood-onset schizophrenia; CRA, childhood rapid-onset ataxia; D-DEMØ, dystonia, dysmorphism of the face, encephalopathy with developmental delay, brain MRI abnormalities always including cerebellar hypoplasia, no hemiplegia (Ø); NKA, Na + ,K + -ATPase; PMG, polymicrogyria; RDP, rapid-onset dystonia-parkinsonism; RECA, relapsing encephalopathy with cerebellar ataxia. G947R Bourgeois et al, 1993;Heinzen et al, 2012;Ito et al, 2018;Jasien et al, 2019;Panagiotakaki et al, 2010;Rosewich et al, 2012;Schirinzi et al, 2018a;Severino et al, 2020 Demos et al, 2014;Duat Rodriguez et al, 2017;Heimer et al, 2015;Maas et al, 2016;Potic et al, 2015;Rosewich et al, 2014c;Stenshorne et al, 2019 Brashear et al, 2012a;Cook et al, 2014;de Carvalho Aguiar et al, 2004;Dobyns et al, 1993;Haq et al, 2019;…”

“…In CAPOS patients, cochlear outer hair cell activity is preserved, but auditory brainstem responses are grossly abnormal ( Tranebjærg et al, 2018 ). All of the reported cases of CAPOS, to date, are heterozygous for a single recurrent missense mutation, E818K ( Demos et al, 2014 ; Duat Rodriguez et al, 2017 ; Han et al, 2017 ; Heimer et al, 2015 ; Maas et al, 2016 ; Potic et al, 2015 ; Rosewich et al, 2014c ; Stenshorne et al, 2019 ). Some CAPOS patients exhibit mild symptoms, resulting in recovery with minimal residual ataxia ( Demos et al, 2014 ), although one subject with a de novo E818K mutation exhibited only sensorineural hearing loss that began when she was a teenager ( Han et al, 2017 ).…”

Cerebellar Ataxia with Progressive Optic Atrophy and Deafness (CAPOS Syndrome): A Rare Case Report

“…CAPOS syndrome, which is derived from the acronym of symptoms like cerebellar ataxia, areflexia, pes cavus, optic atrophy, sensory neural hearing loss, is a very rare disorder; first described in three patients by Nicolaides et al in 1996 1 . Since the original description, about forty patients have been reported and causal association with specific genetic mutation has been established 2 . A missense mutation of the ATP1A3 gene, inherited as autosomal dominant traits with variable expressivity, causes the allelic disorders namely: CAPOS syndrome, rapid -onset dystoniaparkinsonism (RDP) in DYT12 and alternating hemiplegia of childhood (AHC) 3 .…”