Auditory Neuropathy as the Initial Phenotype for Patients With ATP1A3 c.2452 G > A: Genotype–Phenotype Study and CI Management

Objective: The objective of this study is to analyze the genotype–phenotype correlation of patients with auditory neuropathy (AN), which is a clinical condition featuring normal cochlear responses and abnormal neural responses, and ATP1A3 c.2452 G > A (p.E818K), which has been generally recognized as a genetic cause of cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss (CAPOS) syndrome.Methods: Four patients diagnosed as AN by clinical evaluation and otoacoustic emission and auditory brainstem responses were recruited and analyzed by next-generation sequencing to identify candidate disease-causing variants. Sanger sequencing was performed on the patients and their parents to verify the results, and short tandem repeat-based testing was conducted to confirm the biological relationship between the parents and the patients. Furthermore, cochlear implantation (CI) was performed in one AN patient to reconstruct hearing.Results: Four subjects with AN were identified to share a de novo variant, p.E818K in the ATP1A3 gene. Except for the AN phenotype, patients 1 and 2 exhibited varying degrees of neurological symptoms, implying that they can be diagnosed as CAPOS syndrome. During the 15 years follow-up of patient 1, we observed delayed neurological events and progressive bilateral sensorineural hearing loss in pure tone threshold (pure tone audiometry, PTA). Patient 2 underwent CI on his left ear, and the result was poor. The other two patients (patient 3 and patient 4, who were 8 and 6 years old, respectively) denied any neurological symptoms.Conclusion:ATP1A3 p.E818K has rarely been documented in the Chinese AN population. Our study confirms that p.E818K in the ATP1A3 gene is a multiethnic cause of AN in Chinese individuals. Our study further demonstrates the significance of genetic testing for this specific mutation for identifying the special subtype of AN with somewhat favorable CI outcome and offers a more accurate genetic counseling about the specific de novo mutation.

Impact of structured physical therapy intervention on functional recovery in a patient with CAPOS syndrome: a case report

Background CAPOS syndrome (cerebellar ataxia, areflexia, pescavus, optic atrophy, and sensorineural hearing loss) is a rare congenital autosomal dominant disorder. The resulting neurological sequelae of impairments are progressive in nature and may interfere with functional independence, performing activities of daily living (ADL’s), and subsequently, affecting the quality of life (QOL). Since it is an extremely rare disorder, there is a severe dearth in the literature about how specific physiotherapy interventions may affect their functional status. Therefore, our objective was to investigate the effects of proprioceptive neuromuscular facilitation (PNF) and Frenkel’s coordination exercises on functional recovery in a patient with CAPOS syndrome. Case presentation We herein present a case of a 25-year-old Indian male with complaints of generalized body weakness, difficulty visualizing distant objects, nystagmus, progressive sensorineural deafness, and ataxia. He was rehabilitated with a structured/customized physiotherapy protocol consisting of PNF approach and coordination exercises for 4 weeks, 6 days/week, 60 min daily. An improvement in overall functional performance of patient as per post-intervention scores of manual muscle testing, trunk control measurement scale, functional independence measure (components of self-care, transfers, and locomotion), and decline in severity of ataxia on scale for assessment and rating of ataxia scale was observed. Conclusion PNF and Frenkel’s exercises resulted in an improvement in overall functional performance of the patient. Improvement was observed in post-test scores of Manual Muscle Testing (MMT), Trunk Control Measurement Scale (TCMS), and Functional Independence Measure (FIM) for the components of self-care, transfers, and locomotion. Additionally, results also showed a decline in severity of ataxia on post-test scores of scale for the assessment and rating of ataxia (SARA) scale (i.e., from severe to moderate).