Dysphagia characteristics in Huntington's disease patients: insights from the Fiberoptic Endoscopic Evaluation of Swallowing and the Swallowing Disturbances Questionnaire.

BACKGROUND: Huntington's disease (HD) is a neurodegenerative disease characterized by increasing dysphagia as the disease progresses. Specific characteristics of the HD dysphagia are not well defined. OBJECTIVE: To characterize the swallowing disturbances of HD patients, to evaluate the feasibility of Fiberoptic Endoscopic Evaluation of Swallowing (FEES) in assessing dysphagia in HD patients, and to discern the relation between FEES findings and patients' self-report on dysphagia symptoms and swallowing related quality of life (SWAL-QOL). METHOD: A retrospective case series in a tertiary referral center. All recruited HD patients underwent Bed Side Swallowing Evaluation (BSE), FEES, the Unified Huntington's Disease Rating Scale (UHDRS), and the Montreal Cognitive Assessment (MoCA). All completed the Swallowing Disturbances Questionnaire (SDQ) and the SWAL-QOL questionnaire. RESULTS: Fourteen HD patients were recruited. All were able to complete the FEES study. The FEES demonstrated delayed swallowing reflex, solid food residues, and pre/post swallowing spillage in most patients (50%, 53.5%, 83.3%, and 87.5%, respectively). The mean SDQ score was 13.2. Significant correlations were found between the SWAL-QOL fear of eating score; the SDQ oral, pharyngeal, and total scores; and the FEES parameters of pureed and solid food bolus flow time. Significant correlations were also found between the total UHDRS score, the volitional cough score, and the SWAL-QOL disease burden score. CONCLUSION: HD patients exhibit prominent unique oropharyngeal dysphagia features that may serve as a marker of disease progression. The FEES and the SDQ are valuable tools for detecting these features in HD patients with swallowing disturbance.

Two Ethnic Clusters with Huntington Disease in Israel: The Case of Mountain Jews and Karaites.

BACKGROUND: Worldwide prevalence estimates of Huntington disease (HD) vary widely, with no reliable information regarding the Jewish population in Israel. METHODS: This specialized tertiary single-center cross-sectional study assessed clinical, cognitive, and demographic characteristics of 84 HD patients who were treated at the Movement Disorder Unit of the Tel Aviv Medical Center, Israel. RESULTS: Our cohort was composed of one-third Ashkenazi Jews, 27% Mountain Jews (Caucasus Jews), 18% Sephardi Jews, and 21% Karaites, with both Mountain Jews and Karaites over-represented compared to their relevant proportion in the population of the state of Israel, which is less than 1%. No between-group differences were detected regarding the number of CAG (cytosine-adenine-guanine) repeats, age at onset, disease duration, years from symptom onset to diagnosis, gender, years of education, Unified Huntington Disease Rating Scale scores, or the Montreal Cognitive Assessment scores. CONCLUSION: We detected clustering of HD among the population treated at our Medical Center, which has the only specialized HD clinic in the country, with a high percentage of HD among 2 relatively small subpopulations of Jews: Mountain Jews and Karaites.

ADCY5-related dyskinesia: Broader spectrum and genotype-phenotype correlations.

OBJECTIVE: To investigate the clinical spectrum and distinguishing features of adenylate cyclase 5 (ADCY5)-related dyskinesia and genotype-phenotype relationship. METHODS: We analyzed ADCY5 in patients with choreiform or dystonic movements by exome or targeted sequencing. Suspected mosaicism was confirmed by allele-specific amplification. We evaluated clinical features in our 50 new and previously reported cases. RESULTS: We identified 3 new families and 12 new sporadic cases with ADCY5 mutations. These mutations cause a mixed hyperkinetic disorder that includes dystonia, chorea, and myoclonus, often with facial involvement. The movements are sometimes painful and show episodic worsening on a fluctuating background. Many patients have axial hypotonia. In 2 unrelated families, a p.A726T mutation in the first cytoplasmic domain (C1) causes a relatively mild disorder of prominent facial and hand dystonia and chorea. Mutations p.R418W or p.R418Q in C1, de novo in 13 individuals and inherited in 1, produce a moderate to severe disorder with axial hypotonia, limb hypertonia, paroxysmal nocturnal or diurnal dyskinesia, chorea, myoclonus, and intermittent facial dyskinesia. Somatic mosaicism is usually associated with a less severe phenotype. In one family, a p.M1029K mutation in the C2 domain causes severe dystonia, hypotonia, and chorea. The progenitor, whose childhood-onset episodic movement disorder almost disappeared in adulthood, was mosaic for the mutation. CONCLUSIONS: ADCY5-related dyskinesia is a childhood-onset disorder with a wide range of hyperkinetic abnormal movements. Genotype-specific correlations and mosaicism play important roles in the phenotypic variability. Recurrent mutations suggest particular functional importance of residues 418 and 726 in disease pathogenesis.

Patient and caregiver perceptions of the social impact of advanced Parkinson's disease and dyskinesias.

Parkinson's disease (PD) exacts a physical and emotional toll on both patients and family. The aim of this study was to compare patient and caregiver perceptions of the social consequences of basic symptoms of PD and levodopa-induced dyskinesias. Forty patients with PD and dyskinesias and 35 of their caregivers completed a self-report questionnaire on the impact of PD and dyskinesias on their feelings of security and embarrassment and participation in family/social events, and indicated their preference for the "on" (with dyskinesias) or the "off" (without dyskinesias) state. The patients scored significantly higher than the caregivers did on the negative social impact of the disease in general (p = 0.002) and of the dyskinesias in particular (p = 0.03). Nevertheless, the patients expressed a significantly greater preference for the "on" state (83 %) than the caregivers (59 %) (p = 0.03). Preferences turned to be reverse in direction among spouse-caregivers who significantly preferred the "off" state (54 %) than the patients (25 %) (p = 0.04). Although patients have a worse perception of the effects of PD than their caregivers do, they prefer the more independent "on" state, whereas their caregivers prefer the "off" state.

Sensorineural deafness, distinctive facial features, and abnormal cranial bones: a new variant of Waardenburg syndrome?

The Waardenburg syndromes (WS) account for approximately 2% of congenital sensorineural deafness. This heterogeneous group of diseases currently can be categorized into four major subtypes (WS types 1-4) on the basis of characteristic clinical features. Multiple genes have been implicated in WS, and mutations in some genes can cause more than one WS subtype. In addition to eye, hair, and skin pigmentary abnormalities, dystopia canthorum and broad nasal bridge are seen in WS type 1. Mutations in the PAX3 gene are responsible for the condition in the majority of these patients. In addition, mutations in PAX3 have been found in WS type 3 that is distinguished by musculoskeletal abnormalities, and in a family with a rare subtype of WS, craniofacial-deafness-hand syndrome (CDHS), characterized by dysmorphic facial features, hand abnormalities, and absent or hypoplastic nasal and wrist bones. Here we describe a woman who shares some, but not all features of WS type 3 and CDHS, and who also has abnormal cranial bones. All sinuses were hypoplastic, and the cochlea were small. No sequence alteration in PAX3 was found. These observations broaden the clinical range of WS and suggest there may be genetic heterogeneity even within the CDHS subtype.

[Somatization disorder in children and adolescents].

Somatization disorder in children and adolescents is a common anxiety disorder. Errors and delays in diagnosis may incur unnecessary expensive and sometimes dangerous medical workup. We review the epidemiology, clinical features, treatment approaches and prognosis. One case study is presented in order to demonstrate this problematic disorder.