Phenotype And Genotype Of 5 Patients With Charcot-Marie-Tooth Disease At The Onset Of Childhood

Backgrounds and Objectives:Charcot-Marie-Tooth disease is one of the most common inherited peripheral nerve degenerative diseases,the population incidence rate of approximately 1/2500.The disease was first reported by Charcot,Marie and Tooth in 1886,therefore also known as Charcot-Marie-Tooth disease(CMT).Neuropathy and genetic basis of different forms of CMT into the demyelinating type(CMT1 type),axonal type(CMT2 type),autosomal recessive CMT1 type(CMT4 type),intermediate(DI-CMT type)and X-linked dominant or recessive geno type(CMTX type).Most of CMT in adolescent onset,progress is relatively slow,does not affect the life expectancy,mostly from the feet,legs and other parts,to lower limb proximal progress gradually,serious still can to the upper limbs and spinal involvement.Clinical performance for high arches,hammer toes,"crane legs",claw hands,lateral condyle,etc.,lack of the sense of pain,temperature and touch.According to statistics,CMT average onset age was 14 years old,because of the slow progression,average treatment age was 24 years old,patients tend to come on commonly to adult hospital after so many years,few pediatric CMT was reported.In this study,the clinical and genetic aspects of the 5 probands of Charcot-Marie-Tooth disease diagnosed in our hospital during the past 2 years were studied to explore the clinical and genetic characteristics of CMT in childhood.Object and Methods:The clinical data were collected,evaluated as well as EMG examination,gene mutation screening and clinical phenotypic analysis were performed with the methods of the NGS,MLPA and disease database analysis.Results:Patients with clinical manifestations,EMG results conform to the typical characteristics of CMT.Among the probands of all five pedigrees,3 cases have PMP22 gene amplification,are CMT1A types;1 case found a insertion mutation:p.D35delinsVVYT,is CMT1B type;l case found 2 missense mutations:p.A SP113GLY?p.ARG577GLN(composite heterozygous mutation),is CMT4H type.The latter two cases were new mutations,not reported in the literature.Conclusion:1.Charcot-Marie-Tooth disease is a common peripheral neurodegenerative disease,mostly incidence in adolescence,rare onset of childhood,CMT4 type onset of age generally earlier than the CMT1 type,the sooner the age of onset,the faster the degree of progress,resulting in more severe deformities.2.In the present study,one new insert mutation and two new missense mutations(composite heterozygous mutation)were found in 5 probands,which enriched the genotype of CMT.