Prevalence, Mortality, and Cause of Death in Charcot-Marie-Tooth Disease in Korea: A Nationwide, Population-Based Study

ObjectivesThis population-based study aimed to determine age-standardised prevalence of Charcot-Marie-Tooth disease (CMT) across the lifespan using multiple case ascertainment sources.DesignPoint-prevalence epidemiological study in the Auckland Region of New Zealand (NZ).SettingMultiple case ascertainment sources including primary care centres, hospital services, neuromuscular disease registry, community-based organisations and self-referral were used to identify potentially eligible participants.ParticipantsAdults (≥16 years, n=207, 87.7%) and children (<16 years, n=29, 12.3%) with a confirmed clinical or molecular diagnosis of CMT, hereditary sensory neuropathy, hereditary motor neuropathy or hereditary neuropathy with liability to pressure palsies who resided in the Auckland Region of NZ on 1 June 2016.Primary outcomePrevalence per 100 000 persons with 95% CIs by subtype, age and sex were calculated and standardised to the world population.ResultsAge-standardised point prevalence of all CMT cases was 15.7 per 100 000 (95% CI 11.6 to 21.0). Highest prevalence was identified in those aged 50–64 years 25.2 per 100 000 (95% CI 19.4 to 32.6). Males had a higher prevalence (16.6 per 100 000, 95% CI 10.9 to 25.2) than females (14.6 per 100 000, 95% CI 9.6 to 22.4). Prevalence of CMT1A was 6.9 per 100 000 (95% CI 5.6 to 8.4). The majority (93.2%) of cases were identified through medical records, with 6.8% of cases uniquely identified through community sources.ConclusionsA small but significant proportion of people with CMT are not connected to healthcare services. Epidemiological studies using medical records alone to identify cases may risk underestimating prevalence. Further studies using population-based methods and reporting age-standardised prevalence are needed to improve global understanding of the epidemiology of CMT.

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Copy Number Variations in a Population-Based Study of Charcot-Marie-Tooth Disease

BioMed Research International ◽

10.1155/2015/960404 ◽

2015 ◽

Vol 2015 ◽

pp. 1-7 ◽

Cited By ~ 8

Author(s):

Helle Høyer ◽

Geir J. Braathen ◽

Anette K. Eek ◽

Gry B. N. Nordang ◽

Camilla F. Skjelbred ◽

...

Keyword(s):

Peripheral Neuropathy ◽

Copy Number ◽

Genetic Diagnosis ◽

Population Based ◽

Copy Number Variations ◽

Comparative Genomic ◽

Charcot Marie Tooth ◽

Charcot Marie Tooth Disease ◽

Neurodevelopmental Disease ◽

Tooth Disease

Copy number variations (CNVs) are important in relation to diversity and evolution but can sometimes cause disease. The most common genetic cause of the inherited peripheral neuropathy Charcot-Marie-Tooth disease is thePMP22duplication; otherwise, CNVs have been considered rare. We investigated CNVs in a population-based sample of Charcot-Marie-Tooth (CMT) families. The 81 CMT families had previously been screened for thePMP22duplication and point mutations in 51 peripheral neuropathy genes, and a genetic cause was identified in 37 CMT families (46%). Index patients from the 44 CMT families with an unknown genetic diagnosis were analysed by whole-genome array comparative genomic hybridization to investigate the entire genome for larger CNVs and multiplex ligation-dependent probe amplification to detect smaller intragenomic CNVs inMFN2andMPZ. One patient had the pathogenicPMP22duplication not detected by previous methods. Three patients had potentially pathogenic CNVs in theCNTNAP2,LAMA2, orSEMA5A, that is, genes related to neuromuscular or neurodevelopmental disease. Genotype and phenotype correlation indicated likely pathogenicity for theLAMA2CNV, whereas theCNTNAP2andSEMA5ACNVs remained potentially pathogenic. Except thePMP22duplication, disease causing CNVs are rare but may cause CMT in about 1% (95% CI 0–7%) of the Norwegian CMT families.

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Phenotype of Patients With Charcot-Marie-Tooth With the p.His123Arg Mutation in GDAP1 in Northern Finland

Neurology Genetics ◽

10.1212/nxg.0000000000000629 ◽

2021 ◽

Vol 7 (6) ◽

pp. e629

Author(s):

Maria Lehtilahti ◽

Mika Kallio ◽

Kari Majamaa ◽

Mikko Kärppä

Keyword(s):

Age At Onset ◽

Population Based ◽

Disability Score ◽

Pes Cavus ◽

Charcot Marie Tooth ◽

Electrodiagnostic Testing ◽

Charcot Marie Tooth Disease ◽

Family Investigation ◽

Neuropathy Symptom Score ◽

Tooth Disease

Background and ObjectivesMutations in the ganglioside-induced differentiation-associated protein 1 (GDAP1) gene cause autosomal dominant or autosomal recessive forms of Charcot-Marie-Tooth disease (CMT). Our aim was to study the clinical phenotype of patients with CMT caused by heterozygous p.His123Arg in GDAP1.MethodsTwenty-three Finnish patients were recruited from a population-based cohort and through family investigation. Each patient was examined clinically and electrophysiologically. The Neuropathy Symptom Score and the Neuropathy Disability Score (NDS) were used in clinical evaluation.ResultsThe median age at onset of symptoms was 17 years among patients with p.His123Arg in GDAP1. Motor symptoms were markedly more common than sensory symptoms at onset. All patients had distal weakness in lower extremities, and 17 (74%) patients had proximal weakness. Muscle atrophy and pes cavus were also common. Nineteen (82%) patients had sensory symptoms such as numbness or pain. The disease progressed with age, and the NDS increased 8.5 points per decade. Electrodiagnostic testing revealed length-dependent, sensory and motor axonal polyneuropathy. EDx findings were asymmetrical in 14 patients. Genealogic study of the families suggested a founder effect.DiscussionWe found that CMT in patients with p.His123Arg in GDAP1 is relatively mild and slow in progression.

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