Clinical features of CAPOS syndrome caused by maternal ATP1A3 gene variation: a case report / 临床耳鼻咽喉头颈外科杂志

CAPOS syndrome is an autosomal dominant neurological disorder caused by mutations in the ATP1A3 gene. Initial symptoms, often fever-induced, include recurrent acute ataxic encephalopathy in childhood, featuring cerebellar ataxia, optic atrophy, areflflexia, sensorineural hearing loss, and in some cases, pes cavus. This report details a case of CAPOS syndrome resulting from a maternal ATP1A3 gene mutation. Both the child and her mother exhibited symptoms post-febrile induction,including severe sensorineural hearing loss in both ears, ataxia, areflexia, and decreased vision. Additionally, the patient's mother presented with pes cavus. Genetic testing revealed a c. 2452G>A（Glu818Lys） heterozygous mutation in theATP1A3 gene in the patient . This article aims to enhance clinicians' understanding of CAPOS syndrome, emphasizing the case's clinical characteristics, diagnostic process, treatment, and its correlation with genotypeic findings.

Cerebellar ataxia, areflexia, pes cavus, optic atrophy and sensorineural hearing loss syndrome: a case report and literature review / 中华神经科杂志

Objective To summarize the clinical characteristics of a patient with cerebellar ataxia,areflexia,pes cavus,optic atrophy and sensorineural hearing loss (CAPOS) syndrome,followed by relative literature review.Methods The medical history,physical examination and results of relative auxiliary examinations were collected from a CAPOS syndrome patient,who was definitely diagnosed by gene detection.Results The patient was a 20-year-old male,complaining of poor coordination for 19 years,impaired vision for 15 years and hearing loss for 13 years.When he was eleven months old,weakness of four limbs happened after diarrhea but recovered spontaneously a few days later.Then his poor coordination was discovered.His vision has decreased progressively since the age of five and he began to suffer from bilateral hearing loss after fever at the age of seven.Anti-infectious and immunoregulatory treatment was ineffective at that time.Physical examination showed that bilateral visual acuity decreased.Transient horizontal gaze-evoked nystagmus and bilateral hearing loss were detected.Obvious shaking was observed with closed eyes and toes together.Finger-to-nose,finger tracking,heel-knee-tibia and alternate motion tests were slightly inaccurate.Deep tendon reflexes disappeared and no pes cavus was observed.Pure tone audiometry revealed bilateral sensorineural hearing loss.Cranial magnetic resonance imaging indicated bilateral optic atrophy.ATP1A3 gene detection in the patient showed c.2452G＞A (p.Glu818Lys) heterozygous mutation while his parents were detected no such mutation in the same locus.Conclusions As for young patients who suffer from acute cerebellar ataxia after fever,disappeared tendon reflexes,atrophy of optic nerves or sensorineural hearing loss,they should be alerted to CAPOS syndrome when immunomodulating or anti-inflammatory therapy has been proved to be useless.Positive family history and ATP1A3 gene mutation would be beneficial to definite diagnosis.

Cerebellar ataxia, areflexia, pes cavus, optic atrophy and sensorineural hearing loss syndrome: a case report and literature review / 中华神经科杂志

Objective@#To summarize the clinical characteristics of a patient with cerebellar ataxia, areflexia, pes cavus, optic atrophy and sensorineural hearing loss (CAPOS) syndrome, followed by relative literature review.@*Methods@#The medical history, physical examination and results of relative auxiliary examinations were collected from a CAPOS syndrome patient, who was definitely diagnosed by gene detection.@*Results@#The patient was a 20-year-old male, complaining of poor coordination for 19 years, impaired vision for 15 years and hearing loss for 13 years. When he was eleven months old, weakness of four limbs happened after diarrhea but recovered spontaneously a few days later. Then his poor coordination was discovered. His vision has decreased progressively since the age of five and he began to suffer from bilateral hearing loss after fever at the age of seven. Anti-infectious and immunoregulatory treatment was ineffective at that time. Physical examination showed that bilateral visual acuity decreased. Transient horizontal gaze-evoked nystagmus and bilateral hearing loss were detected. Obvious shaking was observed with closed eyes and toes together. Finger-to-nose, finger tracking, heel-knee-tibia and alternate motion tests were slightly inaccurate. Deep tendon reflexes disappeared and no pes cavus was observed. Pure tone audiometry revealed bilateral sensorineural hearing loss. Cranial magnetic resonance imaging indicated bilateral optic atrophy. ATP1A3 gene detection in the patient showed c. 2452G>A (p. Glu818Lys) heterozygous mutation while his parents were detected no such mutation in the same locus.@*Conclusions@#As for young patients who suffer from acute cerebellar ataxia after fever, disappeared tendon reflexes, atrophy of optic nerves or sensorineural hearing loss, they should be alerted to CAPOS syndrome when immunomodulating or anti-inflammatory therapy has been proved to be useless. Positive family history and ATP1A3 gene mutation would be beneficial to definite diagnosis.

Clinical and Genetic Spectrum of ATP1A3-Related Disorders in a Korean Pediatric Population

Phenotypic and genotypic characteristics of fever-induced paroxysmal weakness and encephalopathy caused by ATP1A3 pathogenic variants / 中华儿科杂志

Objective@#To characterize fever-induced paroxysmal weakness and encephalopathy (FIPWE) caused by ATP1A3 gene pathogenic variant.@*Methods@#Phenotypic and genotypic characteristics of 4 FIPWE patients (3 boys and 1 girl), who were ascertained from October 2016 to March 2018 in Beijing Children's Hospital due to ATP1A3 heterozygous variants, were retrospectively analyzed. The whole exsome sequencing was used for genetic testing.@*Results@#The onset ages of 4 patients were 2 years and 9 months, 2 years and 4 months, 8 months, 2 years and 5 months respectively. The episode ranged from 1 to 3 times, and at 3 months to 2 years and 10 months intervals. All 4 patients had symptoms of limb weakness and encephalopathy, accompanied with mild to severe ataxia or athetosis. The tendon reflex was absent in all patients, and the Babinski's sign was positive. Three patients had dysphagia and 3 patients had slurred speech. Three patients had abnormal eye movements, including strabismus and opsoclonus. None of the 4 patients exhibited visual impairment, auditory impairment or talipes cavus. The duration of acute phase ranged from 1 week to 3 months. In 3 relapsing patients, symptoms became progressively worse, with relapses occurring frequently and recovery being more difficult, and various sequelae were found after the last relapse. All patients carried heterozygous variant in ATP1A3 gene. The missense variants result in the substitution of an arginine residue at position 756. Three variants were identified, including C. 2267G > T (p. R756L) (1 case), C. 2266C > T (p. R756C) (2 cases), and C. 2267G > A (p. R756H) (1 case). Three were de novo and one inherited from his father, but the grandparents did not carry the variant. All variants were reported as pathogenic.@*Conclusions@#FIPWE is one of new clinical phenotypes of ATP1A3 spectrum disease and most cases are sporadic. The missense variants result in the substitution of an arginine residue at position 756. This report provided insights into the phenotype-genotype association in patients with FIPWE caused by pathogenic variants of ATP1A3.

Clinical manifestations and advances in hereditary research of alternating hemiplegia of childhood / 国际儿科学杂志

Alternating hemiplegia of childhood(AHC) is a hereditary disease characterized by hemiplegia spells,abnormal eye movements,dystonia and cognitive impairment.There are three phases of the disease.Each phase has its unique clinical symptoms:phase 1-abnormal eye movements and dystonia;phase 2-hemiplegia spells; phase 3-permanent cognitive impairment.The severity of cognitive impairment depends on the time of onset of hemiplegia spells:the earlier the onset is,the worse outcome will be.No effective treatment has been established.Thetreatments currently include:avoiding predisposing factors and taking drugs such as flunarizine to prevent hemiplegia attacks,in the inter-ictal stage;and sedation during hemiplegia attacks.According to the latest research,AHC is caused by the de novo mutation of gene ATP1A3.