Encephalopathic attacks in a family co-segregating myotonic dystrophy type 1, an intermediate Charcot-Marie-Tooth neuropathy and early hearing loss

Spaans, F.; Faber, Catharina G.; Smeets, H.; Hofman, Paul; Braida, C.; Monckton, Darren G.; Die-Smulders, C.E.M. de

doi:10.1136/jnnp.2008.170126

Cited by 7 publications

(6 citation statements)

References 37 publications

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“…In some instances, repeat interruptions are thought to contribute additional phenotypes beyond the typical disease repertoire. In myotonic dystrophy type 1, CCG and GGC repeat interruptions within the 3′ end of the CTG expansion is thought to modify the disease and impart additional phenotypes including neuropathy [16,17]. Additionally, in spinocerebellar ataxia type 2 (SCA2), CAG repeat expansions within Ataxin 2 containing CAA interruptions are found associated with parkinsonism-predominant forms of SCA2 [18–21].…”

Section: Discussionmentioning

confidence: 99%

Repeat interruptions in spinocerebellar ataxia type 10 expansions are strongly associated with epileptic seizures

et al. 2013

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Spinocerebellar ataxia type 10 (SCA10), an autosomal dominant neurodegenerative disorder, is the result of a non-coding, pentanucleotide repeat expansion within intron 9 of the Ataxin 10 gene. SCA10 patients present with pure cerebellar ataxia; yet, some families also have a high incidence of epilepsy. SCA10 expansions containing penta- and heptanucleotide interruption motifs, termed “ATCCT interruptions,” experience large contractions during germline transmission, particularly in paternal lineages. At the same time, these alleles confer an earlier age at onset which contradicts traditional rules of genetic anticipation in repeat expansions. Previously, ATCCT interruptions have been associated with a higher prevalence of epileptic seizures in one Mexican-American SCA10 family. In a large cohort of SCA10 families, we analyzed whether ATCCT interruptions confers a greater risk for developing seizures in these families. Notably, we find that the presence of repeat interruptions within the SCA10 expansion confers a 6.3-fold increase in the risk of an SCA10 patient developing epilepsy (6.2-fold when considering patients of Mexican ancestry only) and a 13.7-fold increase in having a positive family history of epilepsy (10.5-fold when considering patients of Mexican ancestry only). We conclude that the presence of repeat interruptions in SCA10 repeat expansion indicates a significant risk for the epilepsy phenotype and should be considered during genetic counseling.

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Section: Discussionmentioning

confidence: 99%

Repeat interruptions in spinocerebellar ataxia type 10 expansions are strongly associated with epileptic seizures

et al. 2013

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“…Karyotyping also showed no chromosomal abnormality. Recently complex mutations in DMPK were reported as the underlying cause of a sensorimotor neuropathy family with myotonic dystrophy, encephalopathic attacks, and hearing loss [Braida et al, 2010; Spaans et al, 2009]. However, we excluded mutations in DMPK , which falls near 19q13.3 and also sequenced additional candidate genes, including PRX (CMT4F), MED25 (CMT2B2 ), MAG , and EMP3 .…”

Section: Discussionmentioning

confidence: 99%

“…Several patients have been reported to have an unusual incidental combination of two neuromuscular diseases of CMT and muscle diseases, such as myotonic dystrophy, Becker muscular dystrophy (MIM♯ 300376), and facioscapulohumeral muscular dystrophy [Bergmann et al, 2000; Bütefisch et al, 1998; Hodapp et al, 2006; Kim et al, 2010]. Recently, a Dutch CMT neuropathy family that also showed complex phenotypes of myotonic dystrophy, encephalopathic attacks, and hearing loss revealed an atypical complex mutations at the DM1 locus (MIM♯ 160900) [Braida et al, 2010; Spaans et al, 2009]. However, there has not been reported a mutation that causes autosomal dominant peripheral neuropathy, distal myopathy, hoarseness, and hearing loss.…”

Section: Introductionmentioning

confidence: 99%

A complex phenotype of peripheral neuropathy, myopathy, hoarseness, and hearing loss is linked to an autosomal dominant mutation in MYH14

et al. 2011

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Both peripheral neuropathy and distal myopathy are well-established inherited neuromuscular disorders characterized by progressive weakness and atrophy of the distal limb muscles. A complex phenotype of peripheral neuropathy, myopathy, hoarseness and hearing loss was diagnosed in a large autosomal dominant Korean family. A high density SNP-based linkage study mapped the underlying gene to a region on chromosome 19q13.3. The maximum multipoint LOD score was 3.794. Sequencing of 34 positional candidate genes in the segregating haplotype revealed a novel c.2822G>T (p.Arg941Leu) mutation in the gene MYH14, which encodes the nonmuscle myosin heavy chain 14. Clinically we observed a sequential pattern of the onset of muscle weakness starting from the anterior to the posterior leg muscle compartments followed by involvement of intrinsic hand and proximal muscles. The hearing loss and hoarseness followed the onset of distal muscle weakness. Histopathologic and electrodiagnostic studies revealed both chronic neuropathic and myopathic features in the affected patients. While mutations in MYH14 have been shown to cause nonsyndromic autosomal dominant hearing loss (DFNA4), the peripheral neuropathy, myopathy, and hoarseness have not been associated with MYH14. Therefore, we suggest that the identified mutation in MYH14 significantly expands the phenotypic spectrum of this gene.

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“…Spaans and colleagues reported a unique dominant phenotype combining myotonic dystrophy type 1, CMT, encephalopathic attacks, and sensoneurial hearing loss [131][132][133][134]. Median MNCV in 14 patients ranged from 23 to 48 m/s (mean, 37); although individual CMAP values are not indicated, it is specifically stated that in four patients the negative peak of the relevant CMAP was lower than 0.5 mV, which means that the corresponding MNCV value does not reliably represent the degree of demyelination [131].…”

Section: Di-cmt Associated With Mutation In Other Genesmentioning

confidence: 99%

Intermediate Charcot–Marie–Tooth disease: an electrophysiological reappraisal and systematic review

et al. 2017

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Charcot-Marie-Tooth disease (CMT) is the most frequent form of inherited neuropathy with great variety of phenotypes, inheritance patterns, and causative genes. According to median motor nerve conduction velocity (MNCV), CMT is divided into demyelinating (CMT1) with MNCV below 38 m/s, axonal (CMT2) with MNCV above 38 m/s, and intermediate CMT with MNCV between 25 and 45 m/s. In each category, transmission may be autosomal dominant, autosomal recessive, or X-linked. The nosology of intermediate CMT is controversial because of concerns about electrophysiological delimitation. A systematic computer-based literature search was conducted on PubMed, using the following MeSH: (1) intermediate Charcot-Marie-Tooth; (2) X-linked intermediate Charcot-Marie-Tooth; and (3) X-linked Charcot-Marie-Tooth and electrophysiology. We retrieved 225 articles reporting X-linked CMT or intermediate CMT with electrophysiological information. After eligibility, 156 papers were used for this review. In assessing median MNCV, compound muscle action potential (CMAP) amplitudes were taken into account. In cases with attenuated CMAP and wherever possible, proximal median MNCV was used for accurate definition of conduction slowing in the intermediate range. In the vast majority of males with X-linked CMT associated with GJB1 mutation (CMTX1), median MNCV was intermediate. CMT associated with DRP2 mutation is another well-documented X-linked intermediate disorder. Autosomal dominant intermediate CMT (DI-CMT) encompasses 11 different types; six of them with assigned phenotype MIM number and the remaining five being unnumbered. Based on available electrophysiological information, we wonder if DI-CMTA should be reclassified within CMT2. Autosomal recessive intermediate CMT (RI-CMT) covers four numbered MIM phenotypes though, in accordance with reported electrophysiology, two of them (RI-CMTB and RI-CMTD) should probably be reclassified within AR-CMT2. We conclude that intermediate CMT is a complex inherited syndrome, whose characterization requires a specific electrophysiological protocol comprising evaluation of upper limb proximal nerve trunks when distal CMAP amplitudes are reduced, and that an updated version of MIM phenotype numbering is needed.

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Encephalopathic attacks in a family co-segregating myotonic dystrophy type 1, an intermediate Charcot-Marie-Tooth neuropathy and early hearing loss

Cited by 7 publications

References 37 publications

Repeat interruptions in spinocerebellar ataxia type 10 expansions are strongly associated with epileptic seizures

Repeat interruptions in spinocerebellar ataxia type 10 expansions are strongly associated with epileptic seizures

A complex phenotype of peripheral neuropathy, myopathy, hoarseness, and hearing loss is linked to an autosomal dominant mutation in MYH14

Intermediate Charcot–Marie–Tooth disease: an electrophysiological reappraisal and systematic review

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