Dědičné neuropatie (DěN) jsou heterogenní skupinou geneticky podmíněných onemocnění periferních nervů, projevující se u převážné většiny pacientů do 20. roku věku a typicky ve školním věku, mezi 6. a 15. rokem, pomalu progredující svalovou slabostí distálně a později i atrofiemi, dříve a více na dolních končetinách a většinou i různě závažnou poruchou čití s distálním maximem, někdy i trofickými změnami. Začátek obtíží s prvními příznaky onemocnění v předškolním věku nebo i po 20. roce života jsou vzácnější, ale také možné a souvisí to do velké míry s konkrétní genovou poruchou. DěN jsou nejčastějším geneticky podmíněným nervosvalovým onemocněním a v ČR je jimi postiženo asi 4 000 lidí. Dědičné neuropatie nezkracují normální délku života, ale mohou vést k tělesné invalidizaci se ztrátou nebo výrazným zhoršením samostatné chůze a výrazně ovlivňovat kvalitu života i samostatný pohyb i sebeobsluhu. Mentální úroveň je typicky normální. Závažnost postižení je do velké míry závislá na genetické příčině a také na délce trvání nemoci.
Hereditary neuropathies are a heterogeneous group of genetically determined peripheral nerve diseases. In the vast majority of patients, they occur by 20 years of age, most typically during school age between ages 6 and 15, and are manifested by slowly progressive muscle weakness distally and, later on, by atrophies, initially and more predominantly in the lower limbs, as well as by sensory disturbance of varying severity with a distal maximum, sometimes even by trophic changes. The onset of complaints with initial symptoms of the disease in preschool age or after 20 years of age is rarer, but also possible, and is, to a great degree, related to the particular gene disorder. Hereditary neuropathies are the most frequent genetically determined neuromuscular diseases, affecting approximately 4,000 people in the Czech Republic. Hereditary neuropathies do not reduce normal life expectancy, but may lead to physical disability with loss or substantial worsening of independent gait and significantly affect the quality of life as well as self-locomotion and self-care. The intellectual level is typically normal. The severity of disability largely depends on the genetic cause as well as on disease duration.
BACKGROUND AND OBJECTIVES: Charcot-Marie-Tooth disease (CMT) is the most common inherited neuropathy and often presents during childhood. Guidelines for the optimal management of common problems experienced by individuals with CMT do not exist, for either children or adults. We formed the Paediatric CMT Best Practice Guidelines Consortium to develop evidence and consensus-based recommendations for the clinical management of children and adolescents with CMT, with the primary objective of promoting optimal, standardised care globally. METHODS: Development of this clinical practice guideline involved a series of systematic reviews covering 10 clinical questions, modified Delphi methodology involving an international panel of clinicians to generate consensus where evidence did not exist, and application of the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach to evaluate the body of literature and formulate recommendations. RESULTS: The final guideline includes three evidence-based and 31 consensus-based recommendations. They encompass the management of muscle weakness, balance and mobility impairment, sensory symptoms, muscle cramps, impaired upper limb function, respiratory impairment, maintenance of joint range of motion and non-surgical management of joint deformity. Consensus was not achieved in some management areas, reflecting differences in practice between clinicians and healthcare settings, and highlighting the need for further research. CONCLUSIONS: This clinical practice guideline provides practical and implementable guidance on the management of common clinical problems experienced by children with CMT and advocates for improved access to multidisciplinary care. Successful dissemination and implementation of these recommendations will be critical in ensuring their application across multiple healthcare settings.
- MeSH
- Charcotova-Marieova-Toothova nemoc * diagnóza terapie MeSH
- dítě MeSH
- dospělí MeSH
- konsensus MeSH
- lidé MeSH
- mladiství MeSH
- směrnice pro lékařskou praxi jako téma MeSH
- svalová slabost MeSH
- svalové křeče MeSH
- systematický přehled jako téma MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé MeSH
- mladiství MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Hereditárne polyneuropatie predstavujú veľkú skupinu geneticky podmienených neurologických ochorení, prezentujúcich sa heterogénnym klinickým obrazom. Na tieto poruchy pomýšľame hlavne pri pozitívnej rodinnej anamnéze, manifestácii chronickej progredujúcej svalovej slabosti a atrofie svalov na končatinách či prítomnosti typických deformít nohy. V našej práci sme sa bližšie zamerali na najčastejšiu hereditárnu periférnu neuropatiu - Charcotovu-Marieovu-Toothovu chorobu (CMT) a urýchlenie progresie tohto ochorenia v kombinácii s chronickým abúzom alkoholu v kazuistike nášho pacienta.
Hereditary peripheral neuropathies represent a large group of genetic neurological diseases presenting with a heterogeneous clinical picture. We mainly think about these disorders at positive family history, presentation of chronic and progressive muscle weakness, atrophy of the limbs and by the presence of typical foot deformities appears. This article closely focuses on the most common hereditary neuropathy - Charcot-Marie-Tooth (CMT) disease and the accelerated progression of this disease in combination with chronic alcohol abuse in our patient's case report.
- MeSH
- Charcotova-Marieova-Toothova nemoc * diagnóza epidemiologie genetika terapie MeSH
- elektromyografie MeSH
- lidé středního věku MeSH
- lidé MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
- Klíčová slova
- neurografie, péče o nohy,
- MeSH
- Charcotova-Marieova-Toothova nemoc * diagnóza ošetřování MeSH
- deformity nohy (od hlezna dolů) diagnóza ošetřování MeSH
- diferenciální diagnóza MeSH
- elektromyografie MeSH
- lidé středního věku MeSH
- lidé MeSH
- talipes cavus * diagnóza ošetřování MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
Biallelic SBF2 mutations cause Charcot-Marie-Tooth disease type 4B2 (CMT4B2), a sensorimotor neuropathy with autosomal recessive inheritance and association with glaucoma. Since the discovery of the gene mutation, only few additional patients have been reported. We identified seven CMT4B2 families with nine different SBF2 mutations. Revisiting genetic and clinical data from our cohort and the literature, SBF2 variants were private mutations, including exon-deletion and de novo variants. The neuropathy typically started in the first decade after normal early motor development, was predominantly motor and had a rather moderate course. Electrophysiology and nerve biopsies indicated demyelination and excess myelin outfoldings constituted a characteristic feature. While neuropathy was >90% penetrant at age 10 years, glaucoma was absent in ~40% of cases but sometimes developed with age. Consequently, SBF2 mutation analysis should not be restricted to individuals with coincident neuropathy and glaucoma, and CMT4B2 patients without glaucoma should be followed for increased intraocular pressure. The presence of exon-deletion and de novo mutations demands comprehensive mutation scanning and family studies to ensure appropriate diagnostic approaches and genetic counseling.
- MeSH
- biopsie MeSH
- Charcotova-Marieova-Toothova nemoc diagnóza genetika MeSH
- dítě MeSH
- dospělí MeSH
- fenotyp * MeSH
- genetická predispozice k nemoci * MeSH
- genetické asociační studie * metody MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mutace * MeSH
- nereceptorové tyrosinfosfatasy genetika MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
- metaanalýza MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
OBJECTIVE: To present methodical approach of preimplantation genetic diagnosis (PGD) as an option for an unaffected pregnancy in reproductive-age couples who have a genetic risk of the X-linked dominant peripheral neuropathy Charcot-Marie-Tooth type 1 disease. PATIENTS AND METHODS: We performed PGD of X-linked Charcot-Marie-Tooth type 1 disease using haplotyping/indirect linkage analysis, when during analysis we reach to exclude embryos that carry a high-risk haplotype linked to the causal mutation p.Leu9Phe in the GJB1 gene. RESULTS: Within the PGD cycle, we examined 4 blastomeres biopsied from cleavage-stage embryos and recommended 3 embryos for transfer. Two embryos were implanted into the uterus; however, it resulted in a singleton pregnancy with a male descendant. Three years later, the couple returned again with spontaneous gravidity. A chorionic biopsy examination of this gravidity ascertained the female sex and a pericentric inversion of chromosome 5 in 70% of the cultivated foetal cells. CONCLUSION: Using indirect linkage analysis, PGD may help to identify genetic X-linked defects within embryos during screening, thereby circumventing the potential problems with abortion.
- MeSH
- Charcotova-Marieova-Toothova nemoc diagnóza genetika MeSH
- genetická vazba MeSH
- genetické markery MeSH
- genetické testování metody MeSH
- haplotypy MeSH
- konexiny genetika MeSH
- lidé MeSH
- mutace MeSH
- preimplantační diagnóza metody MeSH
- těhotenství MeSH
- Check Tag
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
Hereditary motor and sensory neuropathy-type Lom (HMSNL), also known as CMT4D, a demyelinating neuropathy with late-onset deafness is an autosomal recessive disorder threatening Roma population worldwide. The clinical phenotype was reported in several case reports before the gene discovery. HMSNL is caused by a homozygous founder mutation p.Arg148* in the N-Myc downstream-regulated gene 1. Here, we report findings from the Czech Republic, where HMSNL was found in 12 Czech patients from eight families. In these 12 patients, 11 of the causes were due to p.Arg148* mutation inherited from both parents by the autosomal recessive mechanism. But in one case, the recessive mutation was inherited only from one parent (father) and unmasked owing to an uniparental isodisomy of the entire chromosome eight. The inherited peripheral neuropathy owing to an isodisomy of the whole chromosome pointed to an interesting, less frequent possibility of recessive disease and complications with genetic counseling.
- MeSH
- Charcotova-Marieova-Toothova nemoc diagnóza etnologie genetika patofyziologie MeSH
- dítě MeSH
- dospělí MeSH
- efekt zakladatele MeSH
- exprese genu MeSH
- fenotyp MeSH
- genetické poradenství MeSH
- genotyp MeSH
- geny recesivní MeSH
- hluchota patofyziologie MeSH
- intracelulární signální peptidy a proteiny genetika MeSH
- lidé MeSH
- lidské chromozomy, pár 8 chemie MeSH
- mutace * MeSH
- předškolní dítě MeSH
- proteiny buněčného cyklu genetika MeSH
- Refsumova nemoc diagnóza etnologie genetika patofyziologie MeSH
- Romové * MeSH
- uniparentální disomie * MeSH
- věk při počátku nemoci MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika MeSH
- MeSH
- Charcotova-Marieova-Toothova nemoc * diagnóza rehabilitace terapie MeSH
- chronická zánětlivá demyelinizační polyneuropatie diagnóza rehabilitace terapie MeSH
- diabetická noha etiologie prevence a kontrola MeSH
- diabetické neuropatie * terapie MeSH
- dolní končetina patofyziologie MeSH
- fyzikální stimulace metody MeSH
- fyzioterapie (techniky) MeSH
- Guillainův-Barrého syndrom diagnóza rehabilitace terapie MeSH
- lázně MeSH
- lidé MeSH
- polyneuropatie * diagnóza klasifikace terapie MeSH
- rehabilitace metody MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
BACKGROUND: Inherited peripheral neuropathies (IPN) are the most common inherited neurological condition. It represents a highly heterogeneous group, both clinically and genetically. Targeted disease specific gene panel massively parallel sequencing (MPS) seems to be a useful tool in diagnosis of disorders with high genetic heterogeneity. METHODS: In our study, we have designed, validated and updated our own custom gene panel of all known genes associated with IPN. One hundred and ninety-eight patients have been tested so far. Only patients in whom mutations in more common causes or relevant genes have already been excluded were enrolled. Five consecutive panel designs were prepared according to recent literature search, the last one covering ninety-three genes. Each patient was tested only once. All data were evaluated with at least two different pipelines. RESULTS: In summary, causative mutation has been found in fifty-one patients (26 %). The results were inconclusive in thirty-one (16 %) patients. No variants of likely significance to IPN were found in one hundred and sixteen (58 %) patients. CONCLUSION: MPS gene panel enables testing of all known IPN causes at once with high coverage and at an affordable cost making it truly a method of choice also in IPN. Gene panel testing results in several interesting results and findings.
- MeSH
- Charcotova-Marieova-Toothova nemoc diagnóza genetika MeSH
- cytoplazmatické dyneiny genetika MeSH
- genetické testování metody MeSH
- genotyp MeSH
- hereditární motorické a senzitivní neuropatie genetika MeSH
- intracelulární signální peptidy a proteiny genetika MeSH
- konexiny genetika MeSH
- lidé MeSH
- mutace MeSH
- nemoci periferního nervového systému diagnóza genetika MeSH
- proteiny buněčného cyklu genetika MeSH
- RNA-helikasy genetika MeSH
- věk při počátku nemoci MeSH
- vysoce účinné nukleotidové sekvenování metody MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Hereditary motor and sensory neuropathy type Russe (HMSNR), also called CMT4G, is an autosomal recessive inherited peripheral neuropathy (IPN) caused by a founder mutation in the HK1 gene. HMSNR affects only patients with Roma origin, similar to the better known HMSN type Lom clarified earlier. By testing IPN patients with Roma origin, we realized that HMSNR affects surprisingly many patients in the Czech Republic. HMSNR is one of the most frequent types of IPN in this country and appears to be twice more frequent than HMSNL. Pronounced lower limb atrophies and severe deformities often lead to walking inability in even young patients, but hands are usually only mildly affected even after many years of disease duration. The group of 20 patients with HMSNR presented here is the first report about the prevalence of HMSNR from central Europe.
- MeSH
- Charcotova-Marieova-Toothova nemoc diagnóza etnologie genetika patologie MeSH
- dítě MeSH
- dospělí MeSH
- efekt zakladatele * MeSH
- exprese genu MeSH
- geny recesivní MeSH
- haplotypy MeSH
- hereditární motorické a senzitivní neuropatie diagnóza etnologie genetika patologie MeSH
- heterozygot MeSH
- hexokinasa genetika MeSH
- homozygot MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mutace * MeSH
- předškolní dítě MeSH
- Refsumova nemoc diagnóza etnologie genetika patologie MeSH
- rodokmen MeSH
- Romové * MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika MeSH
