The cerebellar phenotype of Charcot-Marie-Tooth neuropathy type 4C

Skott, Humberto; Muntean-Firanescu, Cristina; Samuelsson, Kristin; Verrecchia, Luca; Svenningsson, Per; Malmgren, Helena; Cananau, Carmen; Espay, Alberto J.; Solders, Göran; Paucar, Martin

doi:10.1186/s40673-019-0103-8

Cited by 11 publications

(10 citation statements)

References 19 publications

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“…Given the complex phenotype of RFC1 CANVAS the differential diagnosis includes genetic and acquired causes of neuropathy, ataxia and vestibular disease. The key differential diagnoses are summarized in Table 2 (26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42).…”

Section: Differential Diagnosismentioning

confidence: 99%

Cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS): genetic and clinical aspects

et al. 2021

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Cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS) typically presents in middle life with a combination of neuropathy, ataxia and vestibular disease, with patients reporting progressive imbalance, oscillopsia, sensory disturbance and a dry cough. Examination identifies a sensory neuropathy or neuronopathy and bilaterally impaired vestibulo-ocular reflex. The underlying genetic basis is of biallelic AAGGG expansions in the second intron of replication factor complex subunit 1 (RFC1). The frequency and phenotype spectrum of RFC1 disease is expanding, ranging from typical CANVAS to site-restricted variants affecting the sensory nerves, cerebellum and/or the vestibular system. Given the wide phenotype spectrum of RFC1, the differential diagnosis is broad. RFC1 disease due to biallelic AAGGG expansions is probably the most common cause of recessive ataxia. The key to suspecting the disease (and prompt genetic testing) is a thorough clinical examination assessing the three affected systems and noting the presence of chronic cough.

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Section: Differential Diagnosismentioning

confidence: 99%

Cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS): genetic and clinical aspects

et al. 2021

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“…Scoliosis is a major feature. CMT4C patients do not manifest with cardiomyopathy, endocrine abnormalities, or increased iron accumulation in the dentate nuclei [ 82 ]. Neuropathy manifests clinically with generalised wasting, muscle hypotonia, pes cavus, and scoliosis.…”

Section: Hereditary Neuropathiesmentioning

confidence: 99%

“…Neuropathy in these patients is of the demyelinating type and slowly progressive. Rarely, cerebellar signs and hypoacusis may be present [ 82 ].…”

Section: Hereditary Neuropathiesmentioning

confidence: 99%

Orphan Peripheral Neuropathies

Finsterer

Löscher

Wanschitz

et al. 2020

Journal of Neuromuscular Diseases

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Objectives: Generally, neuropathies of peripheral nerves are a frequent condition (prevalence 2–3%) and most frequently due to alcoholism, diabetes, renal insufficiency, malignancy, toxins, or drugs. However, the vast majority of neuropathies has orphan status. This review focuses on the etiology, frequency, diagnosis, and treatment of orphan neuropathies. Methods: Literature review Results: Rareness of diseases is not uniformly defined but in the US an orphan disease is diagnosed if the prevalence is <1:200000, in Europe if <5:10000. Most acquired and hereditary neuropathies are orphan diseases. Often the causative variant has been reported only in a single patient or family, particularly the ones that are newly detected (e.g. SEPT9, SORD). Among the complex neuropathies (hereditary multisystem disorders with concomitant neuropathies) orphan forms have been reported among mitochondrial disorders (e.g. NARP, MNGIE, SANDO), spinocerebellar ataxias (e,g, TMEM240), hereditary spastic paraplegias (e.g UBAP1), lysosomal storage disease (e.g. Schindler disease), peroxisomal disorders, porphyrias, and other types (e.g. giant axonal neuropathy, Tangier disease). Orphan acquired neuropathies include the metabolic neuropathies (e.g. vitamin-B1, folic acid), toxic neuropathies (e.g. copper, lithium, lead, arsenic, thallium, mercury), infectious neuropathies, immune-mediated (e.g. Bruns-Garland syndrome), and neoplastic/paraneoplastic neuropathies. Conclusions: Though orphan neuropathies are rare per definition they constitute the majority of neuropathies and should be considered as some of them are easy to identify and potentially treatable, as clarification of the underlying cause may contribute to the knowledge about etiology and pathophysiology of these conditions, and as the true prevalence may become obvious only if all ever diagnosed cases are reported.

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“…Some clinical features of the peripheral nerve involvement are helpful in defining the etiology of the cerebellar ataxia. Among those, we could highlight (1) the neurophysiologic characterization of the nerve involvement, as either axonal or demyelinating; (2) and the distribution pattern of the neuropathy, either lengthdependent or diffuse as in a neuronopathy.…”

Section: Introductionmentioning

confidence: 99%

“…Demyelinating neuropathy in patients with a cerebellar ataxia is particularly uncommon. Very few disorders such as Refsum disease and eventually specific subtypes of Charcot-Marie-Tooth (CMT) patients, like CMT type 4C could lead to a marked peripheral demyelination, with severely reduced conduction velocities [2].…”

Section: Introductionmentioning

confidence: 99%

The Intersection Between Cerebellar Ataxia and Neuropathy: a Proposed Classification and a Diagnostic Approach

et al. 2021

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Neuropathy is a common associated feature of different types of genetic or sporadic cerebellar ataxias. The pattern of peripheral nerve involvement and its associated clinical features can be an invaluable aspect for narrowing the etiologic diagnosis in the investigation of cerebellar ataxias. In this review, we discuss the differential diagnosis of the intersection between peripheral nerve and cerebellar involvement, and classify them in accordance with the predominant features. Genetics, clinical features, neuroimaging, and neurophysiologic characteristics are discussed. Furthermore, a diagnostic approach for cerebellar ataxia with neuropathy is proposed according to the different clinical characteristics. This is an Educational and Descriptive review with the aim of medical education for the approach to the patients with cerebellar ataxia and neuropathy. The diagnostic approach to the patient with cerebellar ataxia with neuropathy requires a detailed medical history, phenotyping, characterization of disease progression and family history. Neuroimaging features and the neurophysiological findings play pivotal roles in defining the diagnosis. Establishing an organized classification method for the disorders based on the clinical features may be very helpful, and could be divided as those with predominant cerebellar features, predominant neuropathic feature, or conditions with both cerebellar ataxia and neuropathy. Second, determining the mode of inheritance is critical on cerebellar ataxias: autosomal dominant and recessive cerebellar ataxias, mitochondrial or sporadic types. Third, one must carefully assess neurophysiologic findings in order to better characterize the predominant pattern of involvement: damage location, mechanism of lesion (axonal or demyelinating), motor, sensory or sensory motor compromise, large or small fibers, and autonomic system abnormalities.

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The cerebellar phenotype of Charcot-Marie-Tooth neuropathy type 4C

Cited by 11 publications

References 19 publications

Cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS): genetic and clinical aspects

Cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS): genetic and clinical aspects

Orphan Peripheral Neuropathies

The Intersection Between Cerebellar Ataxia and Neuropathy: a Proposed Classification and a Diagnostic Approach

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