Patient experiences of receiving a diagnosis of hypermobile Ehlers-Danlos syndrome.

Hypermobile Ehlers-Danlos syndrome (hEDS) presents with a wide range of clinical symptoms and comorbidities that impact quality of life. The diagnosis is challenging and often delayed due to the heterogeneity of the disease and lack of diagnostic biomarkers, which adds to the disease burden by affecting patients' psychosocial adaptation and overall well-being. Previous studies have revealed that healthcare professionals and the public have a limited understanding and familiarity with the condition, which leads to disapproval and skepticism that greatly impact patients' social spheres and welfare.

Very-Long-Chain Acyl-CoA Dehydrogenase Deficiency: Family Impact and Perspectives.

Very-Long-Chain Acyl-CoA Dehydrogenase Deficiency (VLCADD) is a fatty acid oxidation disorder characterized by the decreased ability of the enzyme very-long-chain acyl-CoA dehydrogenase to break down fatty acids with 14 to 20-long carbon chains. The resulting clinical manifestations are variable in severity and include hypoketotic hypoglycemia, rhabdomyolysis, and cardiomyopathy. Treatment can consist of limiting the dietary intake of long-chain fatty acids, the prevention of fasting, and the supplementation of medium-chain fats.

Validation of a suspicion index to identify patients at risk for hereditary angioedema.

Background: Hereditary angioedema (HAE) is a genetic condition characterized by dysregulation of the contact (kallikrein-bradykinin) pathway, leading to recurrent episodes of angioedema.

Objective: This project sought to determine whether a suspicion index screening tool using electronic health record (EHR) data can identify patients with an increased likelihood of a diagnosis of HAE.

Methods: A suspicion index screening tool for HAE was created and validated by using known patients with HAE from the medical literature as well as positive and negative controls from HAE-focused centers.

Thyroid disease in cervical dystonia.

There are many possible etiologies for cervical dystonia (CD), but a cause cannot be identified in most cases. Most recent attention has focused on genetic causes, although a few prior studies have highlighted autoimmune mechanisms instead. Because autoimmune disorders frequently co-exist, the current study evaluated the hypothesis that autoimmune disorders might be more common in CD than neurological controls.

Genetic Referral Patterns and Responses to Clinical Scenarios: A Survey of Primary Care Providers and Clinical Geneticists.

Introduction: Primary care physicians (PCPs) are considered the gatekeepers of genetic services, but they often underutilize or inappropriately utilize such services, leading to lack of early treatment, incorrect diagnoses, and unnecessary procedures. This study aims to delineate PCP referral patterns, including the frequency of, motivators for, and barriers to genetic referrals and testing in the present landscape of genomics.

Methods: A 34-item online survey was distributed to PCPs in the United States (US).

Spinocerebellar Ataxia Patient Perceptions Regarding Reproductive Options.

Background: In vitro fertilization with preimplantation genetic testing is a growing reproductive option for people who want to avoid passing a single-gene condition on to their offspring. The spinocerebellar ataxias are a group of rare, autosomal-dominant neurodegenerative disorders which are strong candidates for the use of this technology.

Objectives: This study aimed to assess knowledge of genetic risk and perceptions of reproductive options in individuals with a diagnosis of spinocerebellar ataxia.

The Changing Age of Individuals Seeking Presymptomatic Genetic Testing for Huntington Disease.

Huntington disease (HD) is a progressive neurodegenerative disorder. Presymptomatic genetic testing allows at-risk individuals to clarify their risk status. Understanding the characteristics and motivations of individuals seeking HD presymptomatic genetic testing better equips genetic counselors and other healthcare professionals to provide comprehensive and personalized care.

Clinical and demographic characteristics related to onset site and spread of cervical dystonia.

Background: Clinical characteristics of isolated idiopathic cervical dystonia such as onset site and spread to and from additional body regions have been addressed in single-site studies with limited data and incomplete or variable dissociation of focal and segmental subtypes. The objectives of this study were to characterize the clinical characteristics and demographics of isolated idiopathic cervical dystonia in the largest standardized multicenter cohort.

Methods: The Dystonia Coalition, through a consortium of 37 recruiting sites in North America, Europe, and Australia, recruited 1477 participants with focal (60.

Clinical and genetic features of cervical dystonia in a large multicenter cohort.

Objective: To characterize the clinical and genetic features of cervical dystonia (CD).

Methods: Participants enrolled in the Dystonia Coalition biorepository (NCT01373424) with initial manifestation as CD were included in this study (n = 1,000). Data intake included demographics, family history, and the Global Dystonia Rating Scale.

Botulinum toxin treatment failures in cervical dystonia: causes, management, and outcomes.

Botulinum toxin (BoNT) is highly effective in the treatment of cervical dystonia (CD), yet a significant proportion of patients report low levels of satisfaction following treatment and fail to follow up for repeated treatments. The goal of this study was to determine the reasons that some patients have unsatisfactory responses. A total of 35 subjects who came to our center requesting alternative treatments due to unsatisfactory responses following BoNT treatment for CD were evaluated.

Development of the Comprehensive Cervical Dystonia Rating Scale: Methodology.

We present the methodology utilized for development and clinimetric testing of the Comprehensive Cervical Dystonia (CD) Rating scale, or CCDRS. The CCDRS includes a revision of the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS-2), a newly developed psychiatric screening tool (TWSTRS-PSYCH), and the previously validated Cervical Dystonia Impact Profile (CDIP-58). For the revision of the TWSTRS, the original TWSTRS was examined by a committee of dystonia experts at a dystonia rating scales workshop organized by the Dystonia Medical Research Foundation.

Clinimetric testing of the comprehensive cervical dystonia rating scale.

Introduction: The aim of this study was to test the clinimetric properties of the Comprehensive Cervical Dystonia Rating Scale. This is a modular scale with modifications of the Toronto Western Spasmodic Torticollis Rating Scale (composed of three subscales assessing motor severity, disability, and pain) now referred to as the revised Toronto Western Spasmodic Torticollis Scale-2; a newly developed psychiatric screening instrument; and the Cervical Dystonia Impact Profile-58 as a quality of life measure.

Methods: Ten dystonia experts rated subjects with cervical dystonia using the comprehensive scale.

Potential mechanisms for low uric acid in Parkinson disease.

Several epidemiologic studies have described an association between low serum uric acid (UA) and Parkinson disease (PD). Uric acid is a known antioxidant, and one proposed mechanism of neurodegeneration in PD is oxidative damage of dopamine neurons. However, other complex metabolic pathways may contribute.

Diagnostic Delays in Spasmodic Dysphonia: A Call for Clinician Education.

Purpose: Spasmodic dysphonia (SD) is a rare but often debilitating disease. Due to lack of awareness among practitioners and lack of well-defined diagnostic criteria, it can be difficult for patients with SD to receive a diagnosis and subsequent treatment. There is currently no literature documenting the efficacy of the medical community in recognizing and diagnosing this disorder.

A multiancestral genome-wide exome array study of Alzheimer disease, frontotemporal dementia, and progressive supranuclear palsy.

Importance: Previous studies have indicated a heritable component of the etiology of neurodegenerative diseases such as Alzheimer disease (AD), frontotemporal dementia (FTD), and progressive supranuclear palsy (PSP). However, few have examined the contribution of low-frequency coding variants on a genome-wide level.

Objective: To identify low-frequency coding variants that affect susceptibility to AD, FTD, and PSP.

Secured web-based video repository for multicenter studies.

Background: We developed a novel secured web-based dystonia video repository for the Dystonia Coalition, part of the Rare Disease Clinical Research network funded by the Office of Rare Diseases Research and the National Institute of Neurological Disorders and Stroke. A critical component of phenotypic data collection for all projects of the Dystonia Coalition includes a standardized video of each participant. We now describe our method for collecting, serving and securing these videos that is widely applicable to other studies.

How long does it take to diagnose cervical dystonia?

Background: Dystonia is a neurological disorder characterized by involuntary twisting movements and postures. The neck is among the most commonly affected regions, and diagnosis can be made readily through a simple clinical evaluation. The goal of this study was to explore how long it took patients to receive a diagnosis of cervical dystonia after symptom onset.

The focal dystonias: current views and challenges for future research.

The most common forms of dystonia are those that develop in adults and affect a relatively isolated region of the body. Although these adult-onset focal dystonias are most prevalent, knowledge of their etiologies and pathogenesis has lagged behind some of the rarer generalized dystonias, in which the identification of genetic defects has facilitated both basic and clinical research. This summary provides a brief review of the clinical manifestations of the adult-onset focal dystonias, focusing attention on less well understood clinical manifestations that need further study.

Disease-related and genetic correlates of psychotic symptoms in Parkinson's disease.

Our aim was to examine disease-related and genetic correlates of the development of psychotic symptoms in a large population of patients with Parkinson's disease. We studied 500 patients with Parkinson's disease from the NeuroGenetics Research Consortium using logistic regression models. Predictors were demographic, clinical (motor/nonmotor features), and genetic, measured as continuous or dichotomous variables.

Paraoxonase-1 polymorphisms in Alzheimer's disease, Parkinson's disease, and AD-PD spectrum diseases.

Paraoxonase-1 (PON1) is a serum arylsulfatase that metabolizes organophosphate pesticides and protects low-density lipoprotein from oxidation. Case-control studies of PON1 genetic variants in Alzheimer's disease (AD) and Parkinson's disease (PD) have revealed some positive albeit inconsistent associations with 2 PON1 coding polymorphisms: Q192R (rs662) and L55M (rs854560). Because AD and PD exist along a spectrum of disorders with shared epidemiologic, clinical, and pathologic features, here we evaluated PON1 variants in a cohort of 746 AD, 566 PD, 132 AD-PD, and 719 cognitively normal age-matched controls.

Postural instability/gait disturbance in Parkinson's disease has distinct subtypes: an exploratory analysis.

Objective: To test the hypothesis that postural instability with falling (PIF) and freezing of gait (FOG) are distinct subtypes of the postural instability/gait disturbance (PIGD) form of Parkinson's disease (PD).

Methods: 499 PD subjects from the NeuroGenetics Research Consortium were studied using logistic regression to examine, in a cross sectional analysis, predictors of FOG and PIF. Potential predictors were from four spheres; demographic, clinical motor, clinical non-motor and genetic.

Variant in the sequence of the LINGO1 gene confers risk of essential tremor.

We identified a marker in LINGO1 showing genome-wide significant association (P = 1.2 x 10(-9), odds ratio = 1.55) with essential tremor.

Prevalence of vitamin d insufficiency in patients with Parkinson disease and Alzheimer disease.

Background: A role for vitamin D deficiency in Parkinson disease (PD) has recently been proposed.

Objective: To compare the prevalence of vitamin D deficiency in a research database cohort of patients with PD with the prevalence in age-matched healthy controls and patients with Alzheimer disease (AD).

Design: Survey study and blinded comparison of plasma 25-hydroxyvitamin D (25[OH]D) concentrations of stored samples in a clinical research database at Emory University School of Medicine.

Evidence of shared risk for Alzheimer's disease and Parkinson's disease using family history.

This case-control study examined the potential for a common etiology of Parkinson's disease (PD) and Alzheimer's disease (AD) using reported family history. Structured interviews were used to collect AD and PD family history from subjects (n = 1,531) with AD, PD, AD/PD, or controls. Intergroup analysis compared reported AD and PD family histories in the three case groups to the histories reported in the control group.

A genetic risk factor for periodic limb movements in sleep.

Background: The restless legs syndrome (RLS) is a common neurologic disorder characterized by an irresistible urge to move the legs. It is a major cause of sleep disruption. Periodic limb movements in sleep are detectable in most patients with RLS and represent an objective physiological metric.