Chapter 27 Frontotemporal dementia
Publication date: 2018 Source:Handbook of Clinical Neurology, Volume 148 Author(s): Jessica Deleon, Bruce L. Miller Frontotemporal dementia (FTD) is a neurodegenerative disorder characterized by progressive changes in behavior, personality, and language with involvement of the frontal and temporal regions of the brain. About 40% of FTD cases have a positive family history, and about 10% of these cases are inherited in an autosomal-dominant pattern. These gene defects present with distinct clinical phenotypes. As the diagnosis of FTD becomes more recognizable, it will become increasingly important to keep these gene mut...
Source: Handbook of Clinical Neurology - February 23, 2018 Category: Neurology Source Type: research
Chapter 26 The genetic landscape of Alzheimer disease
Publication date: 2018 Source:Handbook of Clinical Neurology, Volume 148 Author(s): Susana Carmona, John Hardy, Rita Guerreiro Alzheimer disease (AD), a progressive and neurodegenerative disease, is the most common form of dementia with high incidence in elderly people. Neuropathologically the disease is defined by the combined presence of extracellular amyloid-beta (Aβ) plaques and intracellular neurofibrillary tangles of phosphorylated tau protein. Genetically, the first clues were provided by genetic linkage studies that led to the identification of APP, PSEN1, and PSEN2 mutations as the main causes of autosomal-d...
Source: Handbook of Clinical Neurology - February 23, 2018 Category: Neurology Source Type: research
Chapter 20 Primary familial brain calcifications
Publication date: 2018 Source:Handbook of Clinical Neurology, Volume 147 Author(s): Beatriz Quintáns, Joao Oliveira, María-Jesús Sobrido Primary familial brain calcification (PFBC) is a neurodegenerative disease with characteristic calcium deposits in the basal ganglia and other brain regions. The disease usually presents as a combination of abnormal movements, cognitive and psychiatric manifestations, clinically indistinguishable from other adult-onset neurodegenerative disorders. The differential diagnosis must be established with genetic and nongenetic disorders that can also lead to calcium deposits in encephal...
Source: Handbook of Clinical Neurology - January 9, 2018 Category: Neurology Source Type: research
Chapter 19 Neurodegeneration with brain iron accumulation
Publication date: 2018 Source:Handbook of Clinical Neurology, Volume 147 Author(s): Susan J. Hayflick, Manju A. Kurian, Penelope Hogarth Neurodegeneration with brain iron accumulation (NBIA) comprises a clinically and genetically heterogeneous group of disorders affecting children and adults. These rare disorders are often first suspected when increased basal ganglia iron is observed on brain magnetic resonance imaging. For the majority of NBIA disorders the genetic basis has been delineated, and clinical testing is available. The four most common NBIA disorders include pantothenate kinase-associated neurodegeneration...
Source: Handbook of Clinical Neurology - January 9, 2018 Category: Neurology Source Type: research
Chapter 18 Wilson disease and related copper disorders
Publication date: 2018 Source:Handbook of Clinical Neurology, Volume 147 Author(s): Matthew T. Lorincz Copper is a required cofactor for enzymes in critical metabolic pathways. Mutations in copper metabolism genes or abnormalities in copper metabolism result in disease from copper excess or deficiency. Wilson disease (WD) is an autosomal-recessive disease caused by mutations in the ATP7B gene which encodes a copper-transporting ATPase. Over 500 different WD mutations throughout the ATP7B gene have been described, most of which are missense mutations. Mutations in both ATP7B alleles result in abnormal copper metabolism a...
Source: Handbook of Clinical Neurology - January 9, 2018 Category: Neurology Source Type: research
Chapter 17 Huntington disease
Publication date: 2018 Source:Handbook of Clinical Neurology, Volume 147 Author(s): Rhia Ghosh, Sarah J. Tabrizi Huntington disease is a monogenic neurodegenerative disorder that displays an autosomal-dominant pattern of inheritance. It is characterized by motor, psychiatric, and cognitive symptoms that progress over 15–20 years. Since the identification of the causative genetic mutation in 1993 much has been discovered about the underlying pathogenic mechanisms, but as yet there are no disease-modifying therapies available. This chapter reviews the epidemiology, genetic basis, pathogenesis, presentation, and clinica...
Source: Handbook of Clinical Neurology - January 9, 2018 Category: Neurology Source Type: research
Chapter 16 Inherited dystonias: clinical features and molecular pathways
Publication date: 2018 Source:Handbook of Clinical Neurology, Volume 147 Author(s): Corinne E. Weisheit, Samuel S. Pappas, William T. Dauer Recent decades have witnessed dramatic increases in understanding of the genetics of dystonia – a movement disorder characterized by involuntary twisting and abnormal posture. Hampered by a lack of overt neuropathology, researchers are investigating isolated monogenic causes to pinpoint common molecular mechanisms in this heterogeneous disease. Evidence from imaging, cellular, and murine work implicates deficiencies in dopamine neurotransmission, transcriptional dysregulation, a...
Source: Handbook of Clinical Neurology - January 9, 2018 Category: Neurology Source Type: research
Chapter 15 Essential tremor
Publication date: 2018 Source:Handbook of Clinical Neurology, Volume 147 Author(s): Lorraine N. Clark, Elan D. Louis Essential tremor (ET) is one of the most common neurologic disorders, and genetic factors are thought to contribute significantly to disease etiology. There has been a relative lack of progress in understanding the genetic etiology of ET. This could reflect a number of factors, including the presence of substantial phenotypic and genotypic heterogeneity. Thus, a meticulous approach to phenotyping is important for genetic research. A lack of standardized phenotyping across studies and patient centers like...
Source: Handbook of Clinical Neurology - January 9, 2018 Category: Neurology Source Type: research
Chapter 14 Genetics of Parkinson disease
Publication date: 2018 Source:Handbook of Clinical Neurology, Volume 147 Author(s): Aloysius Domingo, Christine Klein An understanding of the genetic etiology of Parkinson disease (PD) has become imperative for the modern-day neurologist. Although genetic forms cause only a minority of PD, the disease mechanisms they elucidate advance the understanding of idiopathic cases. Moreover, recently identified susceptibility variants contribute to complex-etiology PD and broaden the contribution of genetics beyond familial and early-onset cases. Dominantly inherited monogenic forms mimic idiopathic PD and are caused by mutatio...
Source: Handbook of Clinical Neurology - January 9, 2018 Category: Neurology Source Type: research
Chapter 13 Autosomal-recessive cerebellar ataxias
Publication date: 2018 Source:Handbook of Clinical Neurology, Volume 147 Author(s): Brent L. Fogel The autosomal-recessive cerebellar ataxias comprise more than half of the known genetic forms of ataxia and represent an extensive group of clinically heterogeneous disorders that can occur at any age but whose onset is typically prior to adulthood. In addition to ataxia, patients often present with polyneuropathy and clinical symptoms outside the nervous system. The most common of these diseases is Friedreich ataxia, caused by mutation of the frataxin gene, but recent advances in genetic analysis have greatly broadened th...
Source: Handbook of Clinical Neurology - January 9, 2018 Category: Neurology Source Type: research
Chapter 12 Autosomal-dominant cerebellar ataxias
Publication date: 2018 Source:Handbook of Clinical Neurology, Volume 147 Author(s): Andrew Mundwiler, Vikram G. Shakkottai Spinocerebellar ataxias (SCAs) are a genetically diverse group of dominantly inherited disorders that share clinical features that result from dysfunction and degeneration of the cerebellum and its associated pathways. Although nearly 40 genes are currently recognized to result in SCA, shared mechanisms for disease pathogenesis exist among subsets of the SCAs. The most common SCAs result from a glutamine-encoding CAG repeat in the respective disease genes. This chapter discusses the varied genetic ...
Source: Handbook of Clinical Neurology - January 9, 2018 Category: Neurology Source Type: research
Chapter 11 The CAG –polyglutamine repeat diseases: a clinical, molecular, genetic, and pathophysiologic nosology
Publication date: 2018 Source:Handbook of Clinical Neurology, Volume 147 Author(s): Colleen A. Stoyas, Albert R. La Spada Throughout the genome, unstable tandem nucleotide repeats can expand to cause a variety of neurologic disorders. Expansion of a CAG triplet repeat within a coding exon gives rise to an elongated polyglutamine (polyQ) tract in the resultant protein product, and accounts for a unique category of neurodegenerative disorders, known as the CAG–polyglutamine repeat diseases. The nine members of the CAG–polyglutamine disease family include spinal and bulbar muscular atrophy (SBMA), Huntington disease, ...
Source: Handbook of Clinical Neurology - January 9, 2018 Category: Neurology Source Type: research
Chapter 9 Repeat expansion diseases
Publication date: 2018 Source:Handbook of Clinical Neurology, Volume 147 Author(s): Henry Paulson More than 40 diseases, most of which primarily affect the nervous system, are caused by expansions of simple sequence repeats dispersed throughout the human genome. Expanded trinucleotide repeat diseases were discovered first and remain the most frequent. More recently tetra-, penta-, hexa-, and even dodeca-nucleotide repeat expansions have been identified as the cause of human disease, including some of the most common genetic disorders seen by neurologists. Repeat expansion diseases include both causes of myotonic dystrop...
Source: Handbook of Clinical Neurology - January 9, 2018 Category: Neurology Source Type: research
Chapter 8 Towards precision medicine
Publication date: 2018 Source:Handbook of Clinical Neurology, Volume 147 Author(s): Tanya Bardakjian, Pedro Gonzalez-Alegre The concept of precision medicine, also referred to as individualized or personalized medicine, has recently gained traction in scientific, medical, and public spheres, and is frequently mentioned as the next model of healthcare delivery. Its goal is to integrate unique information obtained from a given patient to customize the care provided to achieve the best possible outcome. Although precision medicine is not fully implemented yet, its application is slowly infiltrating clinical practice, and ...
Source: Handbook of Clinical Neurology - January 9, 2018 Category: Neurology Source Type: research
Chapter 7 Bioinformatics and genomic databases
Publication date: 2018 Source:Handbook of Clinical Neurology, Volume 147 Author(s): Jason Chen, Giovanni Coppola High-throughput, low-cost sequencing technologies have begun to yield new insights into biology and medicine. New data enable the interrogation of the molecular biology of disease from DNA to RNA to protein, charting the central dogma. This chapter reviews some of the key advances and resources in the application of bioinformatics to understanding, and ultimately diagnosing and treating, diseases of the nervous system. Array genotyping, exome sequencing, and whole-genome sequencing, in both disease and healt...
Source: Handbook of Clinical Neurology - January 9, 2018 Category: Neurology Source Type: research
