ACTB gene mutation in combined Dystonia-Deafness syndrome with parkinsonism: Expanding the phenotype and highlighting the long-term GPi DBS outcome.

We report a Dystonia-Deafness syndrome patient treated by pallidal Deep Brain Stimulation with significant long-term benefits. Our study expands and confirms the complex phenotypic spectrum of ACTB gene-related disorders and supports the effectiveness of pallidal stimulation on motor outcomes and quality of life in dystonia due to ACTB p.Arg183Trp heterozygosity.

Identifying and Managing Hearing and Vision Loss in Older People in Care Homes: A Scoping Review of the Evidence.

BACKGROUND AND OBJECTIVES: Poor identification of sensory impairments in care homes can be due to multiple factors. This scoping review identifies and synthesizes the literature into the detection of hearing and vision loss in the care home environment, and the management of these sensory losses once identified. RESEARCH DESIGN AND METHODS: A scoping review methodology was used to identify primary research of any design published from 1985 to September 2018. Six electronic databases were searched, and articles were also sourced from reference lists, relevant charity organizations and published experts. RESULTS: Six electronic databases and multiple gray literature sources identified 51 articles for inclusion. The evidence confirmed that lack of knowledge in care home staff, poor management of assistive aids, unsuitable environment, lack of connections with optometrists and audiologists, underuse of effective screening tools, and the added complexity of assisting those with dementia are all barriers to effective practice. Conversely, flexible training programs, availability of a variety of assistive aids, simple screening tools, and adaptions to the environment are effective facilitators. DISCUSSION AND IMPLICATION: This review acknowledges that the barriers to identification and management of hearing and vision loss in care homes are multifaceted and that collaboration of multiple stakeholders is required to implement change and improve the residents' ear and eye care. Recommendations are offered to support more effective service provision tailored to meet the needs of people with sensory impairments living in care homes, and this could subsequently improve best practice.

Bilateral Globus Pallidus Internus Deep Brain Stimulation in a Case of Progressive Dystonia in Mohr-Tranebjaerg Syndrome with Bilateral Cochlear Implants.

INTRODUCTION: A 28-year-old man presented with a history of sensorineural deafness since early childhood treated with bilateral cochlear implants (CIs). He showed signs of debilitating dystonia that had been present since puberty. Dystonic symptoms, especially a protrusion of the tongue and bilateral hand tremor, had not responded to botulinum toxin therapy. We diagnosed Mohr-Tranebjaerg syndrome (MTS). METHODS AND MATERIAL: Deep brain stimulation (DBS) of the bilateral globus pallidus internus was performed predominantly with stereotaxic computed tomography angiography guidance under general anesthesia. Electrophysiology was used to identify the target regions and to guide DBS electrode placement. RESULTS: In the immediate postoperative course and stimulation, the patient showed marked improvement of facial, extremity, and cervical dystonia. More than 2 years after implantation, his dystonic symptoms had dramatically improved by 82%. DISCUSSION: MTS is a rare genetic disorder leading to sensorineural deafness, dystonia, and other symptoms. The use of DBS for the dystonia in MTS was previously described but not in the presence of bilateral CIs. CONCLUSION: DBS in MTS may be a viable option to treat debilitating dystonic symptoms. We describe successful DBS surgery, despite the presence of bilateral CIs, and stimulation therapy over 2 years.

Dystonia-deafness syndrome caused by ACTB p.Arg183Trp heterozygosity shows striatal dopaminergic dysfunction and response to pallidal stimulation.

BACKGROUND: Dystonia-deafness syndrome is a well-known clinical entity, with sensorineural deafness typically manifesting earlier than dystonia. ACTB p.Arg183Trp heterozygosity has been reported in six patients to cause combined infant-onset deafness and dystonia manifesting in adolescence or young adulthood. Three of these have received beneficial pallidal stimulation. Brain imaging to assess striatal function has not been reported previously, however. Nor has a comprehensive hypothesis been presented for how the pleiotropic manifestations of this specific beta-actin gene mutation originate developmentally. CASE PRESENTATION: A 19-year-old girl with congenital mild dysmorphic facial features, cochlear implants for infant-onset deafness, and mild cognitive and emotional disability, presented with an adolescent-onset, severe generalized dystonia. Brain MRI and multiple single gene sequencing were inconclusive. Due to life-threatening dystonia, we implanted a neurostimulation device, targeting the postero-ventral internal pallidum bilaterally. The Burke-Fahn-Marsden Dystonia Rating Scale motor/disability scores improved from 87/25 to 21/13 at 2.5 months postoperatively, 26/14 at 3 years, and 30/14 at 4 years. Subsequent whole exome sequencing identified heterozygosity for the ACTB p.Arg183Trp variant. Brain imaging included 123I-ioflupane single photon emission computed tomography (Dopamine Transporter-SPECT), SPECT with 123I-epidepride (binds to dopamine type 2-receptors) and 18 Fluoro-Deoxy-Glucose (FDG)-PET. Both Epidepride-SPECT and FDG-PET showed reduced tracer uptake in the striatum bilaterally, particularly in the putamen. DaT-SPECT was slightly abnormal. CONCLUSIONS: In this patient with dystonia-deafness syndrome caused by ACTB p.Arg183Trp heterozygosity, unprecedented brain imaging findings strongly indicate striatal neuronal/dopaminergic dysfunction as the underlying cause of the dystonia. Pallidal stimulation provided a substantial improvement of the severe generalized dystonia, which is largely sustained at 4-year follow-up, and we advise this treatment to be considered in such patients. We hypothesize that the pleiotropic manifestations of the dystonia-deafness syndrome caused by this mutation derive from diverse developmental functions of beta-actin in neural crest migration and proliferation (facial dysmorphogenesis), hair cell stereocilia function (infant-onset deafness), and altered synaptic activity patterns associated with pubertal changes in striatal function (adolescent-onset dystonia). The temporal differences in developmental onset are likely due to varying degrees of susceptibility and of compensatory upregulation of other actin variants in the affected structures.

[The Usher Syndrome, a Human Ciliopathy]. / Das Usher-Syndrom, eine Ziliopathie des Menschen.

The human Usher syndrome (USH) is a complex, rare disease manifesting in its most common form of inherited deaf-blindness. Due to the heterogeneous manifestation of the clinical symptoms, three clinical types (USH1-3) are distinguished according to the severity of the disease pattern. For a correct diagnosis, in addition to the auditory tests in early newborn screening, ophthalmological examinations and molecular genetic analysis are important. Ten known USH genes encode proteins, which are from heterogeneous protein families, interact in functional protein networks. In the eye and in the ear, USH proteins are expressed primarily in the mechano-sensitive hair cells and the rod and cone photoreceptor cells, respectively. In the hair cells, the USH protein networks are essential for the correct differentiation of the hair bundles as well as for the function of the mechano-electrical transduction complex in the matured cell. In the photoreceptor cells, USH proteins are located in the ciliary region and participate in intracellular transport processes. In addition, a USH protein network is present in the so-called calyceal processes. The lack of calyceal processes and the absence of a prominent visual phenotype in the mouse disqualifies mice as models for studies on the ophthalmic component of USH. While hearing impairments can be compensated with hearing aids and cochlear implants, there is no practical therapy for USH in the eye. Currently, gene-based therapy concepts, such as gene addition, applications of antisense oligonucleotides and TRIDs ("translational readthrough inducing drugs") for the readthrough of nonsense mutations are preclinically evaluated. For USH1B/MYO7A the UshStat gene therapy clinical trial is ongoing.

Progressive deafness-dystonia due to SERAC1 mutations: A study of 67 cases.

OBJECTIVE: 3-Methylglutaconic aciduria, dystonia-deafness, hepatopathy, encephalopathy, Leigh-like syndrome (MEGDHEL) syndrome is caused by biallelic variants in SERAC1. METHODS: This multicenter study addressed the course of disease for each organ system. Metabolic, neuroradiological, and genetic findings are reported. RESULTS: Sixty-seven individuals (39 previously unreported) from 59 families were included (age range = 5 days-33.4 years, median age = 9 years). A total of 41 different SERAC1 variants were identified, including 20 that have not been reported before. With the exception of 2 families with a milder phenotype, all affected individuals showed a strikingly homogeneous phenotype and time course. Severe, reversible neonatal liver dysfunction and hypoglycemia were seen in >40% of all cases. Starting at a median age of 6 months, muscular hypotonia (91%) was seen, followed by progressive spasticity (82%, median onset = 15 months) and dystonia (82%, 18 months). The majority of affected individuals never learned to walk (68%). Seventy-nine percent suffered hearing loss, 58% never learned to speak, and nearly all had significant intellectual disability (88%). Magnetic resonance imaging features were accordingly homogenous, with bilateral basal ganglia involvement (98%); the characteristic "putaminal eye" was seen in 53%. The urinary marker 3-methylglutaconic aciduria was present in virtually all patients (98%). Supportive treatment focused on spasticity and drooling, and was effective in the individuals treated; hearing aids or cochlear implants did not improve communication skills. INTERPRETATION: MEGDHEL syndrome is a progressive deafness-dystonia syndrome with frequent and reversible neonatal liver involvement and a strikingly homogenous course of disease. Ann Neurol 2017;82:1004-1015.

Experiences of deafblind people about health care. / Experiencias de las personas sordociegas sobre la atención sanitaria.

Deafblindness is a disability resulting from the combination of visual and auditory sensory impairments, which can manifest in different levels causing special communication problems. Deafblind people have special needs that derive from difficulties in sensing, understanding, attention and a lack of the skills required to function effectively in society. Deafblindness requires specialized services, personnel specifically trained in its care and special methods for communication. OBJECTIVE: The main objective of this study is to explore the experiences of deafblind people in relation to health care throughout their lives. This study was developed at the St. Angela de la Cruz Centre, belonging to the Association of Parents of Deafblind People in Spain. METHOD: Phenomenological qualitative study, through semi-structured interviews with deafblind people at the St. Ángela de la Cruz Centre, Salteras (Seville), carried out in 2015, with the help of interpreters in Spanish sign language. Topics covered in the interviews refer to facilities, human resources, time waiting and health care. RESULTS: Coinciding statements were obtained, where the participants point out architectural and educational barriers in health care and stand out better if the professionals know sign language. CONCLUSIONS: It can be highlighted that healthcare professionals lack knowledge of all aspects of deafblindness, sign language in particular, and there is a shortage of signs and information for the deafblind. Moreover, alternatives are required to reduce waiting times and improve direct communication with health professionals.

Dystonia-deafness syndrome caused by a ß-actin gene mutation and response to deep brain stimulation.

INTRODUCTION: Dystonia-deafness syndrome is a distinct clinical presentation within the dystonia-spectrum. Although several genetic and acquired causes have been reported, etiology remains unknown in the majority of patients. OBJECTIVES: To describe two patients with dystonia-deafness syndrome due to a beta-actin gene mutation. METHODS: We report on disease course, genetic testing, and management of 2 patients, mother and daughter, presenting with dystonia-deafness syndrome. RESULTS: After exclusion of known dystonia-deafness syndrome causes, whole-exome sequencing revealed a beta-actin gene mutation (p.Arg183Trp) in both patients. Although beta-actin gene mutations are generally associated with developmental Baraitser-Winter syndrome, dystonia-deafness syndrome has been reported once in identical twin brothers. Bilateral GPi-DBS led to a significant decrease of dystonia and regain of independency in our patients. CONCLUSION: The p.Arg183Trp mutation in the beta-actin gene is associated with the clinical presentation of dystonia-deafness syndrome, even with only minimal or no developmental abnormalities of Baraitser-Winter syndrome. GPi-DBS should be considered to ameliorate the invalidating dystonia in these patients. © 2016 International Parkinson and Movement Disorder Society.

An Overview of Transition Planning for Students Who Are Deafblind.

Children who are deafblind are one of the lowest-incidence yet most diverse groups receiving services mandated by the Individuals With Disabilities Education Improvement Act. Despite this population's diversity, the development of communication skills is critical for all children who are deafblind, and is the foundation on which good transition planning can be built. The authors describe key research findings and other professional literature on transition planning and services guided by the quality of life principle. The role of the individualized education program and case law in transition planning is discussed. Through a person-centered approach to transition planning, a coordinated set of activities designed to support the young adult in moving from school to postschool settings and activities is identified. The authors conclude that effective transition efforts will involve extensive collaboration among school and agency professionals, families, and the young adult who is deafblind.

Toward a Comprehensive System of Personnel Development in Deafblind Education.

Students who are deafblind are a unique population with unique needs for learning, communication, and environmental access. Two roles have been identified as important to their education: teacher of the deafblind and intervener. However, these roles are not officially recognized in most states. Because of this lack of recognition and the low incidence of deafblindness, it is difficult to sustain systems that prepare highly qualified personnel with advanced training and knowledge in educational strategies for children and youth who are deafblind. The authors propose a comprehensive system of personnel development (CSPD) for deafblind education. The components of this system are standards, preservice training, in-service/professional development, leadership development, research, and, finally, planning coordination, and evaluation. The authors describe elements of the model that are being implemented and provide suggestions to support the future development of a comprehensive system.

Arts syndrome with a novel missense mutation in the PRPS1 gene: A case report.

Arts syndrome is characterized by early-onset hypotonia, ataxia, intellectual disability, sensorineural hearing impairment, progressive optic atrophy, and a tendency to develop infections. Arts syndrome is an X-linked disorder caused by a loss-of-function mutation in the PRPS1 gene, which encodes phosphoribosylpyrophosphate synthetase 1. Only three families have been reported. Here, we report another family with Arts syndrome. The initial symptoms of the 1-year-old proband were hypotonia and ataxia, worsening recurrent infection-triggered muscle weakness, motor and intellectual developmental delay, and hearing loss. Both central nervous system involvement and peripheral neuropathy were demonstrated. His three maternal uncles had died before the age of 3years. A genetic analysis of PRPS1 revealed a novel missense mutation, c.367C>G (p.His123Asp). PRPS enzymatic activity was markedly reduced in the patient. His mother was supposed to be an asymptomatic carrier. Arts syndrome should be included in the differential diagnosis of infantile hypotonia and weakness aggravated by recurrent infection with a family history of X-linked inheritance.

A Young Man With Progressive Vision and Hearing Loss.

A 37-year-old man with a history of progressive bilateral sensorineural hearing loss presented to a neuro-ophthalmology clinic with an acute left homonymous hemianopsia. In this article, we discuss the clinical approach and differential diagnosis of progressive combined vision and hearing loss and guide the reader to discover the patient's ultimate diagnosis.