ABSTRACT
@#X-linked dystonia-parkinsonism (XDP) is an adult-onset debilitating neurodegenerative disorder presenting with motor and nonmotor symptoms. The treatment options for XDP are limited. We described a patient with XDP who underwent a unilateral transcranial magnetic resonance-guided focused ultrasound (tcMRgFUS) pallidothalamic tractotomy with a one-year follow-up. The patient reported an immediate improvement in his pain after the procedure. Compared to baseline, there was an improvement in his scores in the dystonia (31%), parkinsonism (35.1%), and activities of daily living (71%) subscales at 1-year follow up. The overall improvement at one year was 46%. There were no adverse events noted. Additional studies with larger sample size and follow-up would be needed to document its long-term safety and efficacy.
Subject(s)
Dystonic Disorders , Genetic Diseases, X-LinkedABSTRACT
TAF1 gene encodes TATA-box binding protein-associated factor-1, which serves as a scaffold for the assembly of the transcription factor ⅡD and participates in the transcription of many genes in eukaryotic cells. Human TAF1 possesses intrinsic protein kinase activity, histone acetyltransferase activity as well as ubiquitin-activating and conjugating activity, and these activities have been mapped to different domains. Currently, TAF1 has been identified as the causative gene of X-linked dystonia-parkinsonism and X-linked mental retardation. What′s more, a series of functional analysis have demonstrated the importance of TAF1 gene in cell cycle and cell growth, and its relationship with neurodevelopment and tumorigenesis has also been reported. This review summarizes the research progress of TAF1 including structure, phenotypes and biological function.
ABSTRACT
@#X-linked dystonia-parkinsonism (XDP) is a rare, adult-onset, progressive, hereditary neurological movement disorder primarily affecting Filipino men with maternal families from Panay province of the Philippines. Medical treatment modalities currently being used have offered temporary symptomatic relief. Surgical management in the form of bilateral globus pallidi internae (Gpi) deep brain stimulation (DBS) has shown promising results and is increasingly being performed in advanced centers, as reported in international literature. Presented herein is the local experience of seven (7) retrospectively reviewed cases from February 2018 to February 2019 in a tertiary center in the Philippines with a particular focus on anesthetic management. All patients were male, from Panay, and presented with progressive dystonia and parkinsonism. All patients underwent planned bilateral, simultaneous DBS electrode, and implantable pulse generator (IPG) placement performed by a multidisciplinary team. Anesthetic management consisted of Bispectral Index (BIS) guided conscious sedation with low dose propofol and remifentanil infusions with a complete scalp nerve block (SB) at the start of the procedure then shifted to awake monitored anesthesia care during electrode placement, microelectrode recording (MER) and macro stimulation testing. All were put under general anesthesia with a supraglottic airway device during the placement of the internal pulse generator (IPG) in the infraclavicular area. All seven patients had successful localization, and insertion of the DBS electrode and discharged improved. The anesthetic management of the DBS used in these cases warrants further investigation and may lead to standardization of future practice.
Subject(s)
Deep Brain StimulationABSTRACT
BACKGROUND AND OBJECTIVE: X-linked dystonia parkinsonism (XDP, DYT3, MIM #314250) is a neurodegenerative movement disorder found endemically in the Philippines. An SVA retrotransposon insertion mutation has been described in patients with XDP, which requires Southern analysis for detection. However, this method is costly and time-consuming. Hence we developed a PCR-based method and validated it among our local population. METHODS AND RESULTS: A total of 58 samples from 58 patients with a clinical diagnosis of XDP were collected. Other samples were from an obligate female carrier, two unaffected male relatives, and two patients with typical Parkinson’s disease. Primers designed to amplify the SVA retrotransposon found in the DYT3-TAF1 gene (NCBI Accession Number AB191243) were used. All patients were positive for the expected 3229-bp product after PCR amplification. The normal control showed a 599-bp product, while the female carrier showed both the 3229 and 599-bp product. Subsequent RFLP analysis using BamHI verified the presence of the SVA retrotransposon insertion mutation. CONCLUSION: Our results show that large-scale PCR-based testing to screen for genetic diseases with a relatively high prevalence such as XDP is possible in our setting. When followed by RFLP analysis, this can provide genetic confirmation of the diagnosis of XDP and facilitate proper genetic counselling and therapy.
ABSTRACT
Sex-linked dystonia parkinsonism (XDP, DYT3, "Lubag") is an adult-onset, progressive, debilitating movement disorder first described in Filipino males from Panay Island in 1975. XDP manifests predominantly as torsion dystonia, later combined with or sometimes replaced with parkinsonism. Within the Island of Panay, the preva-lence rate is highest in the province of Capiz, where 1:4000 men suffer from the disorder. There is a high degree of penetrance and generalization. While women often serve as carriers, XDP is not limited to men. An updated XDP Philippine registry (as of January 2010) has identified 505 cases, with 500 males and 5 females. While some report that females may carry a milder form of the disorder, in our experience, both sexes generally follow a similar progressive clinical course.