Chapter 42 Neuropathy
Publication date: 2018 Source:Handbook of Clinical Neurology, Volume 148 Author(s): Chiara Pisciotta, Michael E. Shy The genetic neuropathies are a clinically and genetically heterogeneous group of diseases that can broadly be classified into two groups: those in which the neuropathy is the sole or primary part of the disorder (Charcot–Marie–Tooth disease, CMT) and those in which the neuropathy is part of a more generalized neurologic or multisystem disorder (e.g., familial amyloid polyneuropathy, neuropathies associated with mitochondrial diseases, with hereditary ataxias, porphyrias). The former is the most commo...
Source: Handbook of Clinical Neurology - February 23, 2018 Category: Neurology Source Type: research
Chapter 41 Hereditary spastic paraplegia
Publication date: 2018 Source:Handbook of Clinical Neurology, Volume 148 Author(s): Craig Blackstone The hereditary spastic paraplegias (HSPs) are a heterogeneous group of neurologic disorders with the common feature of prominent lower-extremity spasticity, resulting from a length-dependent axonopathy of corticospinal upper motor neurons. The HSPs exist not only in “pure” forms but also in “complex” forms that are associated with additional neurologic and extraneurologic features. The HSPs are among the most genetically diverse neurologic disorders, with well over 70 distinct genetic loci, for which about 60 mut...
Source: Handbook of Clinical Neurology - February 23, 2018 Category: Neurology Source Type: research
Chapter 40 Spinal and bulbar muscular atrophy
Publication date: 2018 Source:Handbook of Clinical Neurology, Volume 148 Author(s): Andrew P. Lieberman Spinal and bulbar muscular atrophy (SBMA) is an adult-onset degenerative disorder of the neuromuscular system resulting in slowly progressive weakness and atrophy of the proximal limb and bulbar muscles. The disease is caused by the expansion of a CAG/glutamine tract in the amino-terminus of the androgen receptor. That SBMA exclusively affects males reflects the fact that critical pathogenic events are hormone-dependent. These include translocation of the polyglutamine androgen receptor from the cytoplasm to the nucle...
Source: Handbook of Clinical Neurology - February 23, 2018 Category: Neurology Source Type: research
Chapter 39 Emerging understanding of the genotype –phenotype relationship in amyotrophic lateral sclerosis
Publication date: 2018 Source:Handbook of Clinical Neurology, Volume 148 Author(s): Stephen A. Goutman, Kevin S. Chen, Ximena Paez-Colasante, Eva L. Feldman Amyotrophic lateral sclerosis (ALS) is a progressive, noncurable neurodegenerative disorder of the upper and lower motor neurons causing weakness and death within a few years of symptom onset. About 10% of patients with ALS have a family history of the disease; however, ALS-associated genetic mutations are also found in sporadic cases. There are over 100 ALS-associated mutations, and importantly, several genetic mutations, including C9ORF72, SOD1, and TARDBP, hav...
Source: Handbook of Clinical Neurology - February 23, 2018 Category: Neurology Source Type: research
Chapter 38 Spinal muscular atrophy
Publication date: 2018 Source:Handbook of Clinical Neurology, Volume 148 Author(s): Eveline S. Arnold, Kenneth H. Fischbeck Autosomal-recessive proximal spinal muscular atrophy (Werdnig–Hoffmann, Kugelberg–Welander) is caused by mutation of the SMN1 gene, and the clinical severity correlates with the number of copies of a nearly identical gene, SMN2. The SMN protein plays a critical role in spliceosome assembly and may have other cellular functions, such as mRNA transport. Cell culture and animal models have helped to define the disease mechanism and to identify targets for therapeutic intervention. The main focus ...
Source: Handbook of Clinical Neurology - February 23, 2018 Category: Neurology Source Type: research
Chapter 37 Genetic basis and phenotypic features of congenital myasthenic syndromes
Publication date: 2018 Source:Handbook of Clinical Neurology, Volume 148 Author(s): Andrew G. Engel The congenital myasthenic syndromes (CMS) are heterogeneous disorders in which the safety margin of neuromuscular transmission is compromised by one or more specific mechanisms. The disease proteins reside in the nerve terminal, the synaptic basal lamina, or in the postsynaptic region, or at multiple sites at the neuromuscular junction as well as in other tissues. Targeted mutation analysis by Sanger or exome sequencing has been facilitated by characteristic phenotypic features of some CMS. No fewer than 20 disease genes ...
Source: Handbook of Clinical Neurology - February 23, 2018 Category: Neurology Source Type: research
Chapter 36 The genetics of congenital myopathies
Publication date: 2018 Source:Handbook of Clinical Neurology, Volume 148 Author(s): Hernan D. Gonorazky, Carsten G. Bönnemann, James J. Dowling Congenital myopathies are a clinically and genetically heterogeneous group of conditions that most commonly present at or around the time of birth with hypotonia, muscle weakness, and (often) respiratory distress. Historically, this group of disorders has been subclassified based on muscle histopathologic characteristics. There has been an explosion of gene discovery, and there are now at least 32 different genetic causes of disease. With this increased understanding of the g...
Source: Handbook of Clinical Neurology - February 23, 2018 Category: Neurology Source Type: research
Chapter 35 Facioscapulohumeral muscular dystrophy
Publication date: 2018 Source:Handbook of Clinical Neurology, Volume 148 Author(s): Rabi Tawil Facioscapulohumeral muscular dystrophy (FSHD) is one of the most common forms of muscular dystrophy with a distinctive pattern of skeletal muscle weakness and a wide spectrum of disease severity. The pathophysiologic consequences of the genetic lesion, the loss of a critical number of macrosatellite repeats (D4Z4) in the subtelomeric region of chromosome 4q35, remained unexplained for almost two decades. Recent studies demonstrate that contraction in the number of D4Z4 repeats results in chromatin relaxation and transcriptiona...
Source: Handbook of Clinical Neurology - February 23, 2018 Category: Neurology Source Type: research
Chapter 34 Disorders of sleep and circadian rhythms
Publication date: 2018 Source:Handbook of Clinical Neurology, Volume 148 Author(s): S.Y. Christin Chong, Lijuan Xin, Louis J. Ptáček, Ying-Hui Fu Sleep is fundamental to the survival of humans. However, knowledge regarding the role of sleep and its regulation is poorly understood. Genetics in flies, mice, and humans has led to a detailed understanding of some aspects of circadian regulation. Sleep homeostasis (the effect of increasing periods of wakefulness on our sleep propensity) is largely not understood. Sleep homeostasis is distinct from, but also linked to, the circadian clock. It is only in the last two deca...
Source: Handbook of Clinical Neurology - February 23, 2018 Category: Neurology Source Type: research
Chapter 33 Episodic ataxias
Publication date: 2018 Source:Handbook of Clinical Neurology, Volume 148 Author(s): Joanna C. Jen, Jijun Wan The familial episodic ataxias (EAs) are prototypical channelopathies in the central nervous system clinically characterized by attacks of imbalance and incoordination variably associated with progressive ataxia and variable interictal features. EA1, EA2, and EA6 are caused by mutations in ion channel- and transporter-encoding genes that regulate neuronal excitability and neurotransmission. (Source: Handbook of Clinical Neurology)
Source: Handbook of Clinical Neurology - February 23, 2018 Category: Neurology Source Type: research
Chapter 32 Periodic paralysis
Publication date: 2018 Source:Handbook of Clinical Neurology, Volume 148 Author(s): Doreen Fialho, Robert C. Griggs, Emma Matthews The periodic paralyses are a group of skeletal muscle channelopathies characterizeed by intermittent attacks of muscle weakness often associated with altered serum potassium levels. The underlying genetic defects include mutations in genes encoding the skeletal muscle calcium channel Cav1.1, sodium channel Nav1.4, and potassium channels Kir2.1, Kir3.4, and possibly Kir2.6. Our increasing knowledge of how mutant channels affect muscle excitability has resulted in better understanding of man...
Source: Handbook of Clinical Neurology - February 23, 2018 Category: Neurology Source Type: research
Chapter 31 Genetics of migraine
Publication date: 2018 Source:Handbook of Clinical Neurology, Volume 148 Author(s): Verneri Anttila, Maija Wessman, Mikko Kallela, Aarno Palotie Genetics of migraine has recently undergone a major shift, moving in the space of a few years from having only a few known genes for rare Mendelian forms to 47 known common variant loci affecting the susceptibility of the common forms of migraine. This has largely been achieved by rapidly increasing sample sizes for genomewide association studies (GWAS), soon to be followed by the first wave of large-scale exome-sequencing studies. The large number of detected loci, chief am...
Source: Handbook of Clinical Neurology - February 23, 2018 Category: Neurology Source Type: research
Chapter 30 Genetics of epilepsy
We present a clinical approach to patients with epilepsy, presenting an algorithm for clinical and genetic testing, and review genes implicated in epilepsy and their associated syndromes. (Source: Handbook of Clinical Neurology)
Source: Handbook of Clinical Neurology - February 23, 2018 Category: Neurology Source Type: research
Chapter 29 Prion disease
Publication date: 2018 Source:Handbook of Clinical Neurology, Volume 148 Author(s): Leonel T. Takada, Mee-Ohk Kim, Stacy Metcalf, Ignacio Illán Gala, Michael D. Geschwind Genetic prion diseases (gPrDs) are caused by autosomal-dominant mutations in the prion protein gene (PRNP). Although the first PRNP mutations identified, and most since, are PRNP missense, octapeptide repeat insertions, deletion and nonsense mutations have now also been shown to cause gPrD. Based on clinicopathologic features of familial disease, gPrDs historically have been classified into three forms: familial Jakob–Creutzfeldt disease, Gerstm...
Source: Handbook of Clinical Neurology - February 23, 2018 Category: Neurology Source Type: research
Chapter 28 The genetics of dementia with Lewy bodies
Publication date: 2018 Source:Handbook of Clinical Neurology, Volume 148 Author(s): Magdalena I. Tolea, James E. Galvin Dementia with Lewy bodies (DLB), the most common non-AD neurodegenerative disease has in the past several decades attracted the attention of the neurological scientific community due to its highly negative impact on the quality of life of both the affected individuals and those caring for them. The strong hereditary component in related conditions such as PD and AD and the description of a number of DLB families suggest that genetic factors may play a role in the pathogenesis of DLB. This chapter focu...
Source: Handbook of Clinical Neurology - February 23, 2018 Category: Neurology Source Type: research
