[Experience in molecular diagnostic in hereditary neuropathies in a pediatric tertiary hospital]

Rev Neurol. 2015 Dec 1;61(11):490-8.
[Article in Spanish]

Abstract

Introduction: Charcot-Marie-Tooth (CMT) is the most common hereditary sensory motor neuropathy. Advances in molecular diagnosis have increased the diagnostic possibilities of these patients.

Patients and methods: Retrospective study of 36 pediatric patients diagnosed with CMT in a tertiary center in 2003-2015.

Results: We found 16 patients were diagnosed by a duplication in PMP22; two cases were diagnosed of hereditary neuropathy with liability to pressure palsies, one with a point mutation in PMP22; a male with a mild demyelinating phenotype, without family history, was diagnosed with GJB1 mutation; in a patient with a peripheral hypotonia at birth and axonal pattern in EMG by mutation in MFN2; a gypsy patient, with consanguineous family, CMT4D, was identified by a mutation in the gene NDRG1; a patient with multiplex congenital arthrogryposis and vocal cord paralysis, whose mother had a scapular-peroneal syndrome, had a congenital spinal muscular atrophy with mild distal axonal neuropathy by mutation in gene TRPV4; three girls, from a gypsy consanguineous family, with axonal CMT with neuromyotonic discharges were diagnosed by a mutation in the gene HINT1; twelve patients haven't molecular diagnosis currently.

Conclusions: CMT1A predominated in our series (44%), as previous studies. We emphasize the description of a patient with a mutation in TRPV4 recently described as a cause of CMT2C and three cases, of gypsy consanguineous family, with the same mutation in HINT1 gene, recently described as a cause of axonal neuropathy with neuromyotonia, autosomal recessive (AR-CMT2). The proportion of patients without molecular diagnosis is similar to main European series.

Title: Experiencia en el diagnostico molecular de neuropatias hereditarias en un hospital pediatrico de tercer nivel.

Introduccion. La enfermedad de Charcot-Marie-Tooth (CMT) es la neuropatia hereditaria sensitivomotora mas frecuente. Avances en el diagnostico molecular han incrementado las posibilidades diagnosticas de estos pacientes. Pacientes y metodos. Estudio retrospectivo de 36 casos pediatricos diagnosticados de CMT en un centro terciario en el periodo 2003-2015. Resultados. Se identificaron 16 pacientes con CMT1A por una duplicacion en PMP22; dos casos se diagnosticaron de neuropatia hereditaria con predisposicion a paralisis por presion, uno de ellos con una mutacion puntual en PMP22; un varon con un fenotipo leve desmielinizante se diagnostico de CMTX1 por mutacion en GJB1; un paciente con una hipotonia paralitica en el nacimiento y un patron axonal por mutacion en MFN2; un paciente de origen rumano se diagnostico de CMT4D por una mutacion en el gen NDRG1; una paciente con una atrofia muscular espinal congenita distal con neuropatia axonal leve asociada por mutacion en el gen TRPV4; tres niñas de una familia consanguinea de etnia gitana se diagnosticaron de CMT axonal con descargas neuromiotonicas por una mutacion en el gen HINT1; 12 pacientes no tienen diagnostico molecular actualmente, cuatro de ellos de etnia gitana. Conclusiones. CMT1A predomino en nuestra serie (44%), como corresponde a la bibliografia. Destacamos la descripcion de una paciente con una mutacion en TRPV4 recientemente descrita como causa de CMT2C y tres casos de una misma familia consanguinea gitana con la misma mutacion en el gen HINT1 recientemente publicada como causa de neuropatia axonal con neuromiotonia autosomica recesiva (AR-CMT2). El porcentaje de casos sin diagnostico molecular es similar al de grandes series europeas.

Publication types

  • English Abstract

MeSH terms

  • Adolescent
  • Cell Cycle Proteins / genetics
  • Charcot-Marie-Tooth Disease / classification
  • Charcot-Marie-Tooth Disease / diagnosis*
  • Charcot-Marie-Tooth Disease / epidemiology
  • Charcot-Marie-Tooth Disease / genetics
  • Child
  • Child, Preschool
  • Connexins / genetics
  • Consanguinity
  • Demyelinating Diseases / diagnosis
  • Demyelinating Diseases / epidemiology
  • Demyelinating Diseases / genetics
  • Female
  • GTP Phosphohydrolases / genetics
  • Gap Junction beta-1 Protein
  • Hereditary Sensory and Motor Neuropathy / diagnosis
  • Hereditary Sensory and Motor Neuropathy / epidemiology
  • Hereditary Sensory and Motor Neuropathy / genetics
  • Hospitals, Pediatric / statistics & numerical data
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics
  • Male
  • Mitochondrial Proteins / genetics
  • Molecular Diagnostic Techniques*
  • Myelin Proteins / genetics
  • Nerve Tissue Proteins / genetics
  • Retrospective Studies
  • Roma / genetics
  • Spain / epidemiology
  • TRPV Cation Channels / genetics
  • Tertiary Care Centers / statistics & numerical data

Substances

  • Cell Cycle Proteins
  • Connexins
  • HINT1 protein, human
  • Intracellular Signaling Peptides and Proteins
  • Mitochondrial Proteins
  • Myelin Proteins
  • N-myc downstream-regulated gene 1 protein
  • Nerve Tissue Proteins
  • PMP22 protein, human
  • TRPV Cation Channels
  • TRPV4 protein, human
  • GTP Phosphohydrolases
  • MFN2 protein, human