A doença de Charcot-Marie-Tooth (CMT), também conhecida como Neuropatia Hereditária Motora e Sensorial (NHMS), é um distúrbio neurológico hereditário que afeta os nervos periféricos responsáveis por transmitir sinais entre o cérebro, a medula espinhal e o restante do corpo.
Introdução
O que você precisa saber de cara
Visão geral
Sinais e sintomas
O quadro clínico inclui manifestações motoras e esqueléticas como fraqueza muscular, fraqueza do músculo quadríceps, fraqueza muscular da cintura escapular, fraqueza da musculatura facial, hipertrofia do músculo esquelético, hipotonia neonatal generalizada, espasticidade e contratura articular da mão, além de movimento limitado do punho e talipes equinovarus bilateral.[1][2]
Alterações neurológicas e de mobilidade abrangem marcha instável, coordenação motora grossa pobre, quedas frequentes, incapacidade de andar, reflexo aquileu diminuído, hiporreflexia de membros superiores e propriocepção distal prejudicada. Podem ser observados também morfologia anormal da pupila, desmielinização periférica, denervação do diafragma, defeito ventilatório restritivo, aumento da concentração de proteína no LCR e anormalidade no EMG.[1][2]
Causas genéticas
A Doença de Charcot-Marie-Tooth intermediária está associada a variantes patogênicas em diversos genes: INF2 (Inverted formin-2), DNM2 (Dynamin-2), KARS1 (Lysine--tRNA ligase), NEFL (Neurofilament light polypeptide), COX6A1 (Cytochrome c oxidase subunit 6A1, mitochondrial), GBF1 (Golgi-specific brefeldin A-resistance guanine nucleotide exchange factor 1), PLEKHG5 (Pleckstrin homology domain-containing family G member 5), GDAP1 (Ganglioside-induced differentiation-associated protein 1), MPZ (Myelin protein P0), YARS1 (Tyrosine--tRNA ligase, cytoplasmic) e GNB4 (Guanine nucleotide-binding protein subunit beta-4).[1][3]
Diagnóstico
A investigação diagnóstica envolve a identificação de alterações neurofisiológicas, como anormalidades no exame de eletromiografia (EMG), e a análise laboratorial do líquido cefalorraquidiano, que pode indicar aumento da concentração de proteína no LCR.[1][2]
A elucidação molecular conta com suporte significativo na literatura e bases de dados, registrando 336 testes genéticos catalogados e 503 variantes listadas na base de dados ClinVar relacionadas aos genes associados.[1][3][4]
Tratamento e manejo
Tratamentos citados na literatura
As seguintes substâncias foram identificadas por meio de mineração de literatura científica na plataforma PubTator3 e representam termos correlacionados em publicações, não constituindo recomendação clínica de tratamento: Chloroquine (5 publicações), Quinine (4 publicações), fanasil pyrimethamine drug combination (3 publicações), Creatinine (2 publicações), Lipids (2 publicações), Resveratrol (2 publicações), acetovanillone (2 publicações), diminazene aceturate (2 publicações), Bortezomib (1 publicação) e Buprenorphine (1 publicação).[4]
Conteúdo informativo gerado e mantido automaticamente a partir de fontes oficiais (Orphanet, HPO, OMIM, SUS). Não substitui avaliação médica.
A Doença de Charcot-Marie-Tooth intermediária é uma neuropatia genética rara caracterizada por alterações mistas na condução dos impulsos pelos nervos periféricos. Ela costuma causar fraqueza muscular, instabilidade ao caminhar, quedas frequentes e dificuldades no movimento das mãos e dos pés. Não existem remédios específicos incorporados ou dispensados pelo SUS para esta apresentação, e a enfermidade não consta na lista oficial de PCDTs de doenças raras do Ministério da Saúde. O acompanhamento das famílias ocorre por meio de avaliação neurológica e suporte aos sintomas na rede de atendimento à saúde.
A doença de Charcot-Marie-Tooth (CMT), também conhecida como Neuropatia Hereditária Motora e Sensorial (NHMS), é um distúrbio neurológico hereditário que afeta os nervos periféricos responsáveis por transmitir sinais entre o cérebro, a medula espinhal e o restante do corpo.
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Entender a doença
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Preparando trilha educativa...
Sinais e sintomas
O que aparece no corpo e com que frequência cada sintoma acontece
Partes do corpo afetadas
+ 62 sintomas em outras categorias
Características mais comuns
Os sintomas variam de pessoa para pessoa. Abaixo estão as 124 características clínicas mais associadas, ordenadas por frequência.
Linha do tempo da pesquisa
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Genética e causas
O que está alterado no DNA e como passa nas famílias
Genes associados
11 genes identificados com associação a esta condição.
Focal segmental glomerulosclerosis 5
A renal pathology defined by the presence of segmental sclerosis in glomeruli and resulting in proteinuria, reduced glomerular filtration rate and progressive decline in renal function. Renal insufficiency often progresses to end-stage renal disease, a highly morbid state requiring either dialysis therapy or kidney transplantation.
Myopathy, centronuclear, 1
A congenital muscle disorder characterized by progressive muscular weakness and wasting involving mainly limb girdle, trunk, and neck muscles. It may also affect distal muscles. Weakness may be present during childhood or adolescence or may not become evident until the third decade of life. Ptosis is a frequent clinical feature. The most prominent histopathologic features include high frequency of centrally located nuclei in muscle fibers not secondary to regeneration, radial arrangement of sarcoplasmic strands around the central nuclei, and predominance and hypotrophy of type 1 fibers.
Charcot-Marie-Tooth disease, recessive intermediate B
A form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Recessive intermediate forms of Charcot-Marie-Tooth disease are characterized by clinical and pathologic features intermediate between demyelinating and axonal peripheral neuropathies, and motor median nerve conduction velocities ranging from 25 to 45 m/sec.
Charcot-Marie-Tooth disease, demyelinating, type 1F
A dominant demyelinating form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Demyelinating neuropathies are characterized by severely reduced nerve conduction velocities (less than 38 m/sec), segmental demyelination and remyelination with onion bulb formations on nerve biopsy, slowly progressive distal muscle atrophy and weakness, absent deep tendon reflexes, and hollow feet. CMT1F is characterized by onset in infancy or childhood (range 1 to 13 years).
Charcot-Marie-Tooth disease, recessive intermediate D
A form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Recessive intermediate forms of Charcot-Marie-Tooth disease are characterized by clinical and pathologic features intermediate between demyelinating and axonal peripheral neuropathies, and motor median nerve conduction velocities ranging from 25 to 45 m/sec.
Charcot-Marie-Tooth disease, axonal, type 2GG
An axonal form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Neuropathies of the CMT2 group are characterized by signs of axonal degeneration in the absence of obvious myelin alterations, normal or slightly reduced nerve conduction velocities, and progressive distal muscle weakness and atrophy. CMT2GG is an autosomal dominant form characterized by slowly progressive distal muscle weakness and atrophy primarily affecting the lower limbs and causing difficulty walking. Some individuals may also have involvement of the hands.
Neuronopathy, distal hereditary motor, autosomal recessive 4
A form of distal hereditary motor neuronopathy, a heterogeneous group of neuromuscular disorders caused by selective degeneration of motor neurons in the anterior horn of the spinal cord, without sensory deficit in the posterior horn. The overall clinical picture consists of a classical distal muscular atrophy syndrome in the legs without clinical sensory loss. The disease starts with weakness and wasting of distal muscles of the anterior tibial and peroneal compartments of the legs. Later on, weakness and atrophy may expand to the proximal muscles of the lower limbs and/or to the distal upper limbs. HMNR4 is characterized by childhood onset, generalized muscle weakness and atrophy with denervation and normal sensation. Bulbar symptoms and pyramidal signs are absent.
Charcot-Marie-Tooth disease, demyelinating, type 4A
A recessive demyelinating form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Demyelinating neuropathies are characterized by severely reduced nerve conduction velocities (less than 38 m/sec), segmental demyelination and remyelination with onion bulb formations on nerve biopsy, slowly progressive distal muscle atrophy and weakness, absent deep tendon reflexes, and hollow feet. By convention autosomal recessive forms of demyelinating Charcot-Marie-Tooth disease are designated CMT4. CMT4A is a severe form characterized by early age of onset and rapid progression leading to inability to walk in late childhood or adolescence.
Charcot-Marie-Tooth disease, demyelinating, type 1B
A dominant demyelinating form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Demyelinating neuropathies are characterized by severely reduced nerve conduction velocities (less than 38 m/sec), segmental demyelination and remyelination with onion bulb formations on nerve biopsy, slowly progressive distal muscle atrophy and weakness, absent deep tendon reflexes, and hollow feet.
Charcot-Marie-Tooth disease, dominant intermediate C
A form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. The dominant intermediate type C is characterized by clinical and pathologic features intermediate between demyelinating and axonal peripheral neuropathies, and motor median nerve conduction velocities ranging from 25 to 45 m/sec.
Charcot-Marie-Tooth disease, dominant intermediate F
A form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. CMTDIF is characterized by onset around adolescence of slowly progressive distal muscle atrophy and weakness affecting the upper and lower limbs and resulting in steppage gait. There is distal sensory impairment with decreased reflexes. Nerve conduction velocities are variable, ranging from the demyelinating to the axonal range.
Variantes genéticas (ClinVar)
503 variantes patogênicas registradas no ClinVar.
Classificação de variantes (ClinVar)
Distribuição de 3 variantes classificadas pelo ClinVar.
Vias biológicas (Reactome)
67 vias biológicas associadas aos genes desta condição.
Diagnóstico
Os sinais que médicos procuram e os exames que confirmam
Tratamento e manejo
Remédios, cuidados de apoio e o que precisa acompanhar
Onde tratar no SUS
Hospitais de referência no Brasil e o protocolo oficial do SUS (PCDT)
🇧🇷 Atendimento SUS — Doença de Charcot-Marie-Tooth intermediária
Selecione um estado ou use sua localização para ver resultados.
Dados de DATASUS/CNES, SBGM, ABNeuro e Ministério da Saúde. Sempre confirme a disponibilidade diretamente com o estabelecimento.
Pesquisa ativa
Ensaios clínicos abertos e novidades científicas recentes
Pesquisa e ensaios clínicos
Nenhum ensaio clínico registrado para esta condição.
Publicações mais relevantes
Novel Biallelic PLEKHG5 Variant Associated With Intermediate Charcot-Marie-Tooth Disease: Case Report From South America.
Biallelic pathogenic variants in PLEKHG5 are associated with two distinct recessive phenotypes, including distal hereditary motor neuropathy AR type 4 and intermediate Charcot-Marie-Tooth disease type C (CMT). No South American cases have been previously reported. We evaluated a male patient with suspected hereditary neuropathy using clinical, electrophysiological, and genetic studies. Symptoms began at 12 years with progressive distal weakness. At 40 years, he had foot drop, pes cavus, distal atrophy, areflexia, and sensory loss to the knees. Disability scales indicated moderate impairment. Electroneuromyography revealed abolished responses in the lower limbs and motor conduction velocities in the intermediate range (35-40 m/s). Genetic analysis identified the homozygous variant c.59G>A (p.Arg20Gln) in PLEKHG5, currently classified as VUS. This reports presents a case from South American linking a homozygous PLEKHG5 variant to recessive intermediate CMT, expanding the geographic and phenotypic spectrum of PLEKHG5-related neuropathies.
ITPR3-associated neuropathy: Report of a further family with adult onset intermediate Charcot-Marie-Tooth disease.
ITPR3 encodes type 3 inositol-tri-phosphate receptor (IP3R3), a protein expressed in Schwann cells, predominantly in the paranodal region, and involved in the regulation of Ca2+ release from the endoplasmic reticulum. Dominant variants in ITPR3 have recently been recognized as a rare cause of intermediate Charcot-Marie-Tooth disease (CMT). We collected the clinical data of a family with autosomal dominant neuropathy whose proband was diagnosed with chronic inflammatory demyelinating polyneuropathy (CIDP) for many years. The genetic diagnosis was achieved by whole exome sequencing. The proband developed symmetrical sensory-motor neuropathy with demyelinating features at 32 years old. He was diagnosed with CIDP and received numerous immunomodulatory treatments. However, his condition progressed, leading to severe proximal leg and hand atrophy that confined him to a wheelchair at 60 years. The patient's two sons began to exhibit symptoms suggestive of neuropathy shortly after age 30 years, and the condition was reoriented as inherited. Exome sequencing identified a heterozygous c.4271C > T variant in the ITPR3 gene segregating with the disease. Nerve conduction studies showed a combination of demyelinating and axonal features that vary by nerve, disease duration, and patient. A uniform thickening of the nerves was identified on nerve echography, as was distal symmetric fatty infiltration in lower limb muscle imaging. The c.4271C > T ITPR3 variant causes a late onset CMT that can be considered an intermediate CMT. Considering the electrophysiological findings and the distribution of IP3R3, we hypothesize that this variant could start as nodal dysfunction that progresses to widespread nerve degeneration.
Correction to: C1orf194 deficiency leads to incomplete early embryonic lethality and dominant intermediate Charcot-Marie-Tooth disease in a knockout mouse model.
A novel single-point mutation of NEFH and biallelic SACS mutation presenting as intermediate form Charcot-Marie-Tooth: A case report in Vietnam.
Charcot-Marie-Tooth disease (CMT) is among the most common group of inherited neuromuscular diseases. SACS mutations were demonstrated to cause autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS). However, there have been few case reports regarding to NEFH and SACS gene mutation to CMT in Vietnamese patients, and the diagnosis of CMT and ARSACS in the clinical setting still overlapped. We report two patients presenting with sensorimotor neuropathy without cerebellar ataxia, spasticity and other neurological features, being diagnosed with intermediate form CMT by electrophysiological and clinical examination and neuroimaging. By whole-exome sequencing panel of two affected members, and PCR Sanger on NEFH and SACS genes to confirm the presence of selected variants on their parents, we identified a novel missense variant NEFH c.1925C>T (inherited from the mother) in an autosomal dominant heterozygous state, and two recessive SACS variants (SACS c.13174C>T, causing missense variant, and SACS c.11343del, causing frameshift variant) (inherited one from the mother and another from the father) in these two patients. Clinical and electrophysiological findings on these patients did not match classical ARSACS. To the best of our knowledge, this is the first case report of two affected siblings diagnosed with CMT carrying both a novel NEFH variant and biallelic SACS variants. We concluded that this novel NEFH variant is likely benign, and biallelic SACS mutation (c.13174C>T and c.11343del) is likely pathogenic for intermediate form CMT. This study is also expected to emphasize the current knowledge of intermediate form CMT, ARSACS, and the phenotypic spectrum of NEFH-related and SACS-related disorders. We expect to give a new understanding of CMT; however, further research should be conducted to provide a more thorough knowledge of the pathogenesis of CMT in the future.
Homozygous N-terminal missense variant in PLEKHG5 associated with intermediate CMT: A case report.
Mutations in PLEKHG5, a pleckstrin homology domain containing member of the GEF family, are associated with distal spinal muscular atrophy and intermediate Charcot-Marie-Tooth disease. Here, we describe an isolated case with distal intermediate neuropathy with scapular winging. By whole exome sequencing, we identified the homozygous PLEKHG5 Arg97Gln missense mutation, located in the N-terminal region of the protein. This mutation resides between a zinc-finger motif and a RBD domain, involved in binding rnd3, a RhoA effector protein. We conclude that based on the characteristic phenotype presented by the patient and the supportive genetic findings, the PLEKHG5 mutation is the causative variant.
Publicações recentes
Novel Biallelic PLEKHG5 Variant Associated With Intermediate Charcot-Marie-Tooth Disease: Case Report From South America.
ITPR3-associated neuropathy: Report of a further family with adult onset intermediate Charcot-Marie-Tooth disease.
A novel single-point mutation of NEFH and biallelic SACS mutation presenting as intermediate form Charcot-Marie-Tooth: A case report in Vietnam.
Homozygous N-terminal missense variant in PLEKHG5 associated with intermediate CMT: A case report.
📚 EuropePMC21 artigos no totalmostrando 18
Novel Biallelic PLEKHG5 Variant Associated With Intermediate Charcot-Marie-Tooth Disease: Case Report From South America.
Journal of the peripheral nervous system : JPNSITPR3-associated neuropathy: Report of a further family with adult onset intermediate Charcot-Marie-Tooth disease.
European journal of neurologyA novel single-point mutation of NEFH and biallelic SACS mutation presenting as intermediate form Charcot-Marie-Tooth: A case report in Vietnam.
Surgical neurology internationalHomozygous N-terminal missense variant in PLEKHG5 associated with intermediate CMT: A case report.
Journal of neuromuscular diseasesPrecision mouse models of Yars/dominant intermediate Charcot-Marie-Tooth disease type C and Sptlc1/hereditary sensory and autonomic neuropathy type 1.
Journal of anatomyLeukoencephalopathy and conduction blocks in PLEKHG5-associated intermediate CMT disease.
Neuromuscular disorders : NMDNovel variants broaden the phenotypic spectrum of PLEKHG5-associated neuropathies.
European journal of neurologyC1orf194 deficiency leads to incomplete early embryonic lethality and dominant intermediate Charcot-Marie-Tooth disease in a knockout mouse model.
Human molecular genetics[Analysis of a pedigree with autosomal dominant intermediate Charcot-Marie-Tooth disease type E and nephropathy].
Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical geneticsATP1A1 mutations cause intermediate Charcot-Marie-Tooth disease.
Human mutationNovel GARS mutation presenting as autosomal dominant intermediate Charcot-Marie-Tooth disease: Intermediate or axonal?
Journal of the peripheral nervous system : JPNSNovel GARS mutation presenting as autosomal dominant intermediate Charcot-Marie-Tooth disease.
Journal of the peripheral nervous system : JPNSA novel missense variant (Gln220Arg) of GNB4 encoding guanine nucleotide-binding protein, subunit beta-4 in a Japanese family with autosomal dominant motor and sensory neuropathy.
European journal of medical geneticsAnatomical distributional defects in mutant genes associated with dominant intermediate Charcot-Marie-Tooth disease type C in an adenovirus-mediated mouse model.
Neural regeneration researchIntermediate Charcot-Marie-Tooth disease: an electrophysiological reappraisal and systematic review.
Journal of neurologyNEFL N98S mutation: another cause of dominant intermediate Charcot-Marie-Tooth disease with heterogeneous early-onset phenotype.
Journal of neurologyVariants in the genes DCTN2, DNAH10, LRIG3, and MYO1A are associated with intermediate Charcot-Marie-Tooth disease in a Norwegian family.
Acta neurologica ScandinavicaNEFL E396K mutation is associated with a novel dominant intermediate Charcot-Marie-Tooth disease phenotype.
Journal of neurologyAssociações
Organizações que acompanham esta doença — pra ter apoio e orientação
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Doença com base genética
Um médico geneticista pode ajudar no diagnóstico de Doença de Charcot-Marie-Tooth intermediária e no aconselhamento genético da família.
Doenças relacionadas
Doenças com sintomas parecidos — ajudam quem ainda está buscando diagnóstico
Perguntas frequentes
O que as famílias mais perguntam sobre esta doença — cada resposta com a fonte de onde saiu
A enfermidade decorre de mutações genéticas em diferentes genes, tais como INF2, DNM2, NEFL, MPZ e PLEKHG5. Mais de 500 variantes genéticas já foram catalogadas e associadas a esse perfil neuropático.
Referências
Fontes citadas no texto, publicações do grafo e bases de dados usadas neste verbete
5 fontes citadas no texto · 5 publicações do grafo RarasNet (PubMed) · 5 bases de dados. Títulos, periódicos e PMIDs vêm direto da fonte, sem intermediação de IA.
Dados compilados pelo RarasNet a partir de fontes abertas (Orphanet, OMIM, MONDO, PubMed/EuropePMC, ClinicalTrials.gov, DATASUS, PCDT/MS). Este conteúdo é informativo e não substitui avaliação médica.
Citar este verbete
Raras. (2026). Doença de Charcot-Marie-Tooth intermediária. Em Raras — Enciclopédia de Doenças Raras do Brasil. https://raras.org/doenca/doenca-de-charcot-marie-tooth-intermediaria
Formato APA. Conteúdo sob CC BY 4.0 — reuso livre com atribuição.
Conteúdo mantido por Agente Raras · Médicos e pesquisadores podem colaborar
Doença de Charcot-Marie-Tooth intermediária
📋 Origem dos dados
Esta página agrega dados de fontes públicas e oficiais. Dados sobre cobertura no SUS (PCDT, CEAF) são verificados ativamente por agente proativo (ver badge no infobox). Demais dados têm atribuição de fonte + data da última sincronização — clique para abrir o original.
- Doença rara (ontologia)
- fonte: Orphanet
- Identificador unificado
- fonte: MONDO
- CID-11 (futuro)
- fonte: WHO ICD-11
- NIH/GARD
- fonte: GARD (NIH)
- Dado público estruturado
- fonte: Wikidata
