HSANs: Clinical Features, Pathologic Classification, and Molecular Genetics

Klein, Christopher J.; Dyck, Peter James

doi:10.1016/b978-0-7216-9491-7.50081-8

Cited by 11 publications

(5 citation statements)

References 154 publications

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“…Examinations such as brain magnetic resonance imaging and respiratory function tests were further performed in patients if there were corresponding symptoms. Patients were grouped to have classic CMT if both motor and sensory nerves were equally involved, dHMN if the involvements were predominant in motor nerves, HSAN if involvements were predominant in sensory and/or autonomic nerves, and HNPP if episodic, recurrent focal neuropathies occurred [14–16]. Classic CMT was subdivided into the demyelinating form (CMT1) for the median MNCV ≤ 38 m/s and the axonal form (CMT2) for the median MNCV > 38 m/s.…”

Section: Methodsmentioning

confidence: 99%

Genotype and phenotype distribution of 435 patients with Charcot–Marie–Tooth disease from central south China

Xie

Lin

Liu

et al. 2021

Euro J of Neurology

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Background and purpose The purpose was to provide an overview of genotype and phenotype distribution in a cohort of patients with Charcot–Marie–Tooth disease (CMT) and related disorders from central south China. Methods In all, 435 patients were enrolled and detailed clinical data were collected. Multiplex ligation‐dependent probe amplification for PMP22 duplication/deletion and CMT multi‐gene panel sequencing were performed. Whole exome sequencing was further applied in the remaining patients who failed to achieve molecular diagnosis. Results Among the 435 patients, 216 had CMT1, 14 had hereditary neuropathy with pressure palsies (HNPP), 178 had CMT2, 24 had distal hereditary motor neuropathy (dHMN) and three had hereditary sensory and autonomic neuropathy (HSAN). The overall molecular diagnosis rate was 70%: 75.7% in CMT1, 100% in HNPP, 64.6% in CMT2, 41.7% in dHMN and 33.3% in HSAN. The most common four genotypes accounted for 68.9% of molecular diagnosed patients. Relatively frequent causes were missense changes in PMP22 (4.6%) and SH3TC2 (2.3%) in CMT1; and GDAP1 (5.1%), IGHMBP2 (4.5%) and MORC2 (3.9%) in CMT2. Twenty of 160 detected pathogenic variants and the associated phenotypes have not been previously reported. Broad phenotype spectra were observed in six genes, amongst which the pathogenic variants in BAG3 and SPTLC1 were detected in two sporadic patients presenting with the CMT2 phenotype. Conclusions Our results provided a unique genotypic and phenotypic landscape of patients with CMT and related disorders from central south China, including a relatively high proportion of CMT2 and lower occurrence of PMP22 duplication. The broad phenotype spectra in certain genes have advanced our understanding of CMT.

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Section: Methodsmentioning

confidence: 99%

Genotype and phenotype distribution of 435 patients with Charcot–Marie–Tooth disease from central south China

Xie

Lin

Liu

et al. 2021

Euro J of Neurology

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“…HSAN is a group of severe disorders affecting peripheral sensory and autonomic neurons with considerable clinical and genetic heterogeneity . A prominent hallmark of virtually all patients is the presence of prominent small‐fiber sensory loss (A‐delta and/or C‐fibers).…”

Section: Inherited Neuropathies Involving Only Peripheral Nervous Systemmentioning

confidence: 99%

“…Classification within HSAN is based on the mode of inheritance and clinical features, including the initial histopathologic descriptions, and the genetic causes (Table ) . HSAN is currently divided into 5 groups .…”

Section: Inherited Neuropathies Involving Only Peripheral Nervous Systemmentioning

confidence: 99%

Inherited neuropathies: Clinical overview and update

2013

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Inherited neuropathy is a group of common neurologic disorders with heterogeneous clinical presentations and genetic causes. Detailed neuromuscular evaluations, including nerve conduction studies, laboratory testing, and histopathologic examination, can assist in identification of the inherited component beyond family history. Genetic testing increasingly enables definitive diagnosis of specific inherited neuropathies. Diagnosis, however, is often complex, and neurologic disability may have both genetic and acquired components in individual patients. The decision of which genetic test to order or whether to order genetic tests is often complicated, and the strategies to maximize the value of testing are evolving. Apart from rare inherited metabolic neuropathies, treatment approaches remain largely supportive. We provide a clinical update of the various types of inherited neuropathies, their differential diagnoses, and distinguishing clinical features (where available). A framework is provided for clinical evaluations, including the inheritance assessment, electrophysiologic examinations, and specific genetic tests.

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“…Most of these individuals can be diagnosed with one of several Hereditary Sensory and Autonomic Neuropathies (HSAN I-IV) (Klein et al, 2005). The majority of these patients have HSAN I which is autosomal-dominant and usually becomes clinically apparent in early adulthood.…”

Section: Introductionmentioning

confidence: 99%

Two novel mutations of SCN9A (Nav1.7) are associated with partial congenital insensitivity to pain

Staud

Price

Janicke

et al. 2011

European Journal of Pain

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Insensitivity to pain is a rare disorder that is commonly associated with Hereditary and Sensory Autonomic Neuropathies (HSAN I -V) resulting often in autonomic dysfunction and premature death. Very few individuals have been reported with pain insensitivity lacking such autonomic neuropathies. We performed genetic, neurologic, psychological, and psychophysical evaluations in such an individual (OMIM 243000) and her first degree relatives. Sequence analysis of genomic DNA revealed two novel SCN9A mutations in this index case (IC). One was a non-conservative missense mutation (C1719R) in exon 26 present only in the IC and one parent. Further sequence analysis of the child's DNA revealed a 1-bp splice donor deletion in intron 17 which was also present in the other parent and one sibling. Detailed psychophysical testing was used to phenotypically characterize the IC, her family members, and 10 matched normal controls. Similar to family members and controls the IC showed normal somatosensory functioning for nonnociceptive mechanoreception and warmth. However, she demonstrated diminished ability to detect cool temperatures combined with profound deficits in heat and mechanical nociception. Congenital insensitivity to pain in our IC was associated with two novel SCN9A mutations which most likely resulted in a Nav1.7 channelopathy. However, in contrast to individuals with other SCN9A mutations, the observed pain insensitivity was relative and not absolute, which may be consistent with hypomorphic effects of one or both mutations. The ability to sense at least some danger signals may be advantageous and ameliorate the otherwise increased morbidity and mortality of some individuals with congenital insensitivity to pain.

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HSANs: Clinical Features, Pathologic Classification, and Molecular Genetics

Cited by 11 publications

References 154 publications

Genotype and phenotype distribution of 435 patients with Charcot–Marie–Tooth disease from central south China

Genotype and phenotype distribution of 435 patients with Charcot–Marie–Tooth disease from central south China

Inherited neuropathies: Clinical overview and update

Two novel mutations of SCN9A (Nav1.7) are associated with partial congenital insensitivity to pain

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