Case Report: Oculomotor Palsy With Cyclic Spasms in a Patient With Charcot-Marie-Tooth Disease Type 1.
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SUBMITTER: Weber KP
PROVIDER: S-EPMC11182204 | biostudies-literature | 2021
REPOSITORIES: biostudies-literature
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Case Report: Oculomotor Palsy With Cyclic Spasms in a Patient With Charcot-Marie-Tooth Disease Type 1.
Weber Konrad P KP Bockisch Christopher J CJ Landau Klara K
Frontiers in ophthalmology 20211001
Oculomotor palsy with cyclic spasms is an extremely rare condition whose exact pathophysiology remains a mystery. We followed a boy from the onset of symptoms at the age of ten months until 15 years and documented the case with video oculography. In addition, he was diagnosed with hereditary motor and sensory neuropathy (Charcot-Marie-Tooth disease type 1). Although a pure coincidence cannot be ruled out, it is conceivable that the underlying demyelinating neuropathy of this patient rendered the ...[more]
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| S-EPMC6862922 | biostudies-literature
Project description:Charcot-Marie-Tooth (CMT) disease is a heterogeneous group of genetic disorders presenting with the phenotype of a chronic progressive neuropathy affecting both the motor and sensory nerves. During the last decade over two dozen genes have been identified in which mutations cause CMT. The disease illustrates a multitude of genetic principles, including diverse mutational mechanisms from point mutations to copy number variation (CNV), allelic heterogeneity, age-dependent penetrance and variable expressivity. Population based studies have determined the contributions of the various genes to disease burden enabling evidence-based approaches to genetic testing.
| S-EPMC2947101 | biostudies-literature
Project description:BackgroundCharcot-Marie-Tooth disease is a spectrum of inherited disorders characterized by both motor and sensory manifestations, which include prominent distal muscle weakness, foot deformities (pes cavus and hammer toes), and sensory deficits. Postural tremor as a manifestation of Charcot-Marie-Tooth is seldom present, except in a variant of Charcot-Marie-Tooth subtype 1 (Roussy-Levy syndrome), and its presence often results in a diagnostic dilemma.Case presentationWe present a 34-year-old Eritrean man who came to our hospital with a complaint of tremors of the hands of 6 months duration. Associated with this, he had difficulty walking and weakness of the distal extremities bilaterally, prominently involving the lower limbs. The patient denied a family history of such illness. Physical examination revealed distal muscle weakness (4+/5 on upper limbs, while 3/5 on lower limbs bilaterally), pes cavus deformity, absent ankle reflexes, and mild vibratory sensory loss. We noted a postural tremor that attenuated when the patient assumed an anatomic position. The tremor was limited to the hands. Nerve conduction study of upper and lower limbs showed moderate to severe motor axonal and demyelinating polyneuropathy (axonal > demyelinating), suggestive of mixed axonal and demyelinating hereditary polyneuropathy. Subsequently, genetic testing revealed copy number changes (heterozygous deletion) on the MPZ and MFN2, while the PMP22 gene showed ambiguous copy number changes (decrease) on exons 2 and 3. Tying the clinical, electrophysiologic, and genetic findings, consideration of Charcot-Marie-Tooth subtype 2A with postural tremor was made. Subsequently, the patient was managed with regular physiotherapy and an anxiolytic resulting in minimal symptom improvement.ConclusionThe present case describes a 34-year-old male patient with Charcot-Marie-Tooth subtype 2A presenting with neuropathic postural tremor, which is a rare presentation of a common hereditary polyneuropathy. This case highlights the fact that tremors can be associated with peripheral neuropathy syndromes, and a high index of suspicion is needed to rightly diagnose our patients.
| S-EPMC11600610 | biostudies-literature
Project description:RationaleCharcot-Marie-Tooth disease (CMT) is a group of hereditary neuropathies with clinical features of muscle atrophy, sensory loss, and foot deformities. CMT is related to a number of genes, such as peripheral myelin protein 22 gene (PMP22). Missense mutations, small deletion mutations, and duplications of PMP22 are common in CMT patients, but few insertion mutation cases of PMP22 have been reported.Patient concernsA 26-year-old male patient with the complaint of general weakness, peroneal atrophy, and deformities in the extremities visited our hospital. The patient was born with bilateral thumbs and feet dystonia. Additionally, delayed feet arch development and delayed walking was observed when he was a child.DiagnosisUsing whole-exome sequencing and electrophysiological test, we identified a novel insertion mutation of PMP22 (NM_153322, c.54_55insGTGCTG, p.(L19delinsVLL)) in a 26-year-old male patient with peroneal atrophy and nerve conduction was not elicited in electromyography (EMG) study. The Protein Variation Effect Analyzer (PROVEAN) program analysis predicted that the variant is likely to be "deleterious." SWISS-MODEL program predicted that alpha helix in original location was disrupted by inserted 6 bases, which may account for the occurrence of CMT3.InterventionsThe patient received symptomatic and supportive treatments, and routine rehabilitation exercises during hospitalization.OutcomesThe condition of the patient was improved, but the disease could not be cured. At 1- and 3-months follow-up, manifestations of the patient were unchanged, and he could take care of himself.LessonsOur findings link a novel PMP22 mutation with a clinical diagnosis of CMT3. The link between gene variation and CMT phenotype may help to reveal the structure and function of PMP22 protein and the pathogenesis of CMT. This study adds further support to the heterogeneity of PMP22 related CMT and provides solid functional evidence for the pathogenicity of the p.(L19delinsVLL) PMP22 variant. Moreover, with the development of high-throughput sequencing technology, the combination of next-generation sequencing (NGS) and conventional Sanger sequencing is becoming one of the comprehensive, inexpensive, and convenient tools for genetic diagnosis of CMT.
| S-EPMC7982204 | biostudies-literature
Project description:Charcot-Marie-Tooth (CMT) disease is a common neurogenetic disorder and its heterogeneity is a challenge for genetic diagnostics. The genetic diagnostic procedures for a CMT patient can be explored according to the electrophysiological criteria: very slow motor nerve conduction velocity (MNCV) (<15 m/s), slow MNCV (15-25 m/s), intermediate MNCV (25-45 m/s), and normal MNCV (>45 m/s). Based on the inheritance pattern, intermediate CMT can be divided into dominant (DI-CMT) and recessive types (RI-CMT). GJB1 is currently considered to be associated with X-linked DI-CMT, and MPZ, INF2, DNM2, YARS, GNB4, NEFL, and MFN2 are associated with autosomal DI-CMT. Moreover, GDAP1, KARS, and PLEKHG5 are associated with RI-CMT. Identification of these genes is not only important for patients and families but also provides new information about pathogenesis. It is hoped that this review will lead to a better understanding of intermediate CMT and provide a detailed diagnostic procedure for intermediate CMT.
| S-EPMC5562560 | biostudies-other
Project description:The 1.4Mb tandem-duplication in the PMP22 gene at 17p11.2 usually manifests as hereditary sensorimotor polyneuropathy with foot deformity, sensorineural hearing-loss, moderate developmental delay, and gait disturbance. Hypertelorism and marked phenotypic variability within a single family has not been reported. In a single family, the PMP22 tandem-duplication manifested as short stature, sensorimotor polyneuropathy, tremor, ataxia, sensorineural hearing-loss, and hypothyroidism in the 27 years-old index case, as mild facial dysmorphism, muscle cramps, tinnitus, intention tremor, bradydiadochokinesia, and sensorimotor polyneuropathy in the 31 year-old half-brother of the index-patient, and as sensorimotor polyneuropathy and foot-deformity in the father of the two. The half-brother additionally presented with hypertelorism, not previously reported in PMP22 tandem-duplication carriers. The presented cases show that the tandem-duplication 17p11.2 may present with marked intra-familial phenotype variability and that mild facial dysmorphism with stuck-out ears and hypertelorism may be a rare phenotypic feature of this mutation. The causal relation between facial dysmorphism and the PMP22 tandem-duplication, however, remains speculative.
| S-EPMC3321337 | biostudies-other
Project description:BackgroundWhole-genome sequencing may revolutionize medical diagnostics through rapid identification of alleles that cause disease. However, even in cases with simple patterns of inheritance and unambiguous diagnoses, the relationship between disease phenotypes and their corresponding genetic changes can be complicated. Comprehensive diagnostic assays must therefore identify all possible DNA changes in each haplotype and determine which are responsible for the underlying disorder. The high number of rare, heterogeneous mutations present in all humans and the paucity of known functional variants in more than 90% of annotated genes make this challenge particularly difficult. Thus, the identification of the molecular basis of a genetic disease by means of whole-genome sequencing has remained elusive. We therefore aimed to assess the usefulness of human whole-genome sequencing for genetic diagnosis in a patient with Charcot-Marie-Tooth disease.MethodsWe identified a family with a recessive form of Charcot-Marie-Tooth disease for which the genetic basis had not been identified. We sequenced the whole genome of the proband, identified all potential functional variants in genes likely to be related to the disease, and genotyped these variants in the affected family members.ResultsWe identified and validated compound, heterozygous, causative alleles in SH3TC2 (the SH3 domain and tetratricopeptide repeats 2 gene), involving two mutations, in the proband and in family members affected by Charcot-Marie-Tooth disease. Separate subclinical phenotypes segregated independently with each of the two mutations; heterozygous mutations confer susceptibility to neuropathy, including the carpal tunnel syndrome.ConclusionsAs shown in this study of a family with Charcot-Marie-Tooth disease, whole-genome sequencing can identify clinically relevant variants and provide diagnostic information to inform the care of patients.
| S-EPMC4036802 | biostudies-literature
Project description:RationaleCharcot-Marie-Tooth (CMT) disease, a hereditary motor and sensory neuropathy, presents with progressive chronic sensory and distal motor polyneuropathy. While sensorineural hearing loss and vestibular impairment have been documented in CMT patients, concurrent middle ear cholesteatoma and persistent direction-changing positional nystagmus have not.Patient concernsThis study details a 22-year-old man with CMT1 exhibiting these symptoms.DiagnosesA 22-year-old man with CMT1 (PMP22, c.319+1G>T mutation) presented with rotatory vertigo, left-sided hearing loss, and aural fullness. Examination revealed middle ear effusion and a whitish mass behind the left tympanic membrane. Audiometry showed mixed hearing loss on the left side. Imaging indicated middle ear cholesteatoma and facial nerve hypertrophy.InterventionsSurgical removal of the cholesteatoma revealed a dehiscent hypertrophied facial nerve.OutcomesPostoperative follow-up showed improved hearing and no recurrence.LessonsThis case highlights 3 key points: facial nerve hypertrophy in CMT requiring differentiation from schwannoma, the first reported instance of middle ear cholesteatoma in a CMT patient, and vertigo due to acute otitis media complicated by serous labyrinthitis, manifesting as direction-changing positional nystagmus. These findings underscore the need for thorough diagnosis and management in such presentations. This is the first report of concomitant middle ear cholesteatoma in a CMT patient, illustrating the complexity of diagnosis and treatment.
| S-EPMC11557088 | biostudies-literature
Project description:ObjectiveThe development of a disease-specific patient-reported outcome for Charcot-Marie-Tooth disease is an important step in the preparation for therapeutic trials. This study describes the development of the Charcot-Marie-Tooth Health Index (CMTHI).MethodsInherited Neuropathy Consortium Contact Registry participants were queried on the symptoms that most impacted their lives. The CMTHI was developed based on these responses. Factor analysis, assessment of test-retest reliability, known group validity, and patient interviews were utilized to refine the instrument.ResultsThe final CMTHI contains 18 themes that capture Charcot-Marie-Tooth disease (CMT) burden. The CMTHI has a high internal consistency and test-retest reliability. The CMTHI was able to discriminate between patient groups expected to have different disease burden. The CMTHI was able to discriminate levels of disability as measured by the CMT examination score and the mobility-Disability Severity Index.InterpretationThe CMTHI represents a valid and reliable outcome to assess patient-reported disease burden in CMT. Ann Neurol 2018;84:225-233.
| S-EPMC6168418 | biostudies-literature
Project description:Monogenic diabetes, which encompasses neonatal diabetes (NDM), maturity onset diabetes of the young (MODY), and several diabetes-associated syndromes, primarily arises from impaired function or abnormal development of the islets of Langerhans, particularly pancreatic β-cells responsible for insulin secretion. This condition is typically associated with a single pathogenic genetic mutation. Charcot-Marie-Tooth disease type 1A (CMT1A) is a hereditary demyelinating neuropathy that is caused by a duplication of the PMP22 gene located on chromosome 17. Herein, we report a case of a young Chinese patient with MODY6 harboring a novel mutation (c. 317C>T, p. Ala106Val) in the NEUROD1 gene. Additionally, this patient concurrently presents with CMT1A, which is characterized by a large segmental duplication within the exon of the PMP22 gene and its adjacent regions. Considering the patient's compromised islet function, we treat him with insulin and oral hypoglycemic agents (metformin, acarbose). This represents the first reported instance of a patient with NEUROD1-MODY coexisting with CMT1A.
| S-EPMC11867909 | biostudies-literature