Dataset Information

Italian cohort of Lafora disease: Clinical features, disease evolution, and genotype-phenotype correlations.

ABSTRACT:

Background

Lafora disease (LD) is characterized by progressive myoclonus, refractory epilepsy, and cognitive deterioration. This complex neurodegenerative condition is caused by pathogenic variants in EPM2A/EPM2B genes, encoding two essential glycogen metabolism enzymes known as laforin and malin. Long-term follow-up data are lacking. We describe the clinical features and genetic findings of a cohort of 26 Italian patients with a long clinical follow-up.

Methods

Patients with EPM2A/EPM2B pathogenic variants were identified by direct gene sequencing or gene panels with targeted re-sequencing. Disease progression, motor functions, and mental performance were assessed by a simplified disability scale. Spontaneous/action myoclonus severity was scored by the Magaudda Scale.

Results

Age range was 12.2-46.2 years (mean:25.53 ± 9.14). Age at disease onset ranged from 10 to 22 years (mean:14.04 ± 2.62). The mean follow-up period was 11.48 ± 7.8 years. Twelve out of the 26 (46%) patients preserved walking ability and 13 (50%) maintained speech. A slower disease progression with preserved ambulation and speech after ≥4 years of follow-up was observed in 1 (11%) out of the 9 (35%) EPM2A patients and in 6 (35%) out of the 17 (65%) EPM2B patients. Follow-up was >10 years in 7 (41.2%) EPM2B individuals, including two harbouring the homozygous p.(D146N) pathogenic variant.

Conclusions

This study supports an overall worse disease outcome with severe deterioration of ambulation and speech in patients carrying EPM2A mutations. However, the delayed onset of disabling symptoms observed in the EPM2B subjects harbouring the p.(D146N) pathogenic variant suggests that the underlying causative variant may still influence LD severity.

SUBMITTER: Riva A

PROVIDER: S-EPMC8166462 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature

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Publications

Italian cohort of Lafora disease: Clinical features, disease evolution, and genotype-phenotype correlations.

Riva Antonella A Orsini Alessandro A Scala Marcello M Taramasso Vittoria V Canafoglia Laura L d'Orsi Giuseppe G Di Claudio Maria Teresa MT Avolio Carlo C D'Aniello Alfredo A Elia Maurizio M Franceschetti Silvana S Di Gennaro Giancarlo G Bisulli Francesca F Tinuper Paolo P Tappatà Maria M Romeo Antonino A Freri Elena E Marini Carla C Costa Cinzia C Sofia Vito V Ferlazzo Edoardo E Magaudda Adriana A Veggiotti Pierangelo P Gennaro Elena E Pistorio Angela A Minetti Carlo C Bianchi Amedeo A Striano Salvatore S Michelucci Roberto R Zara Federico F Minassian Berge Arakel BA Striano Pasquale P

Journal of the neurological sciences 20210320

<h4>Background</h4>Lafora disease (LD) is characterized by progressive myoclonus, refractory epilepsy, and cognitive deterioration. This complex neurodegenerative condition is caused by pathogenic variants in EPM2A/EPM2B genes, encoding two essential glycogen metabolism enzymes known as laforin and malin. Long-term follow-up data are lacking. We describe the clinical features and genetic findings of a cohort of 26 Italian patients with a long clinical follow-up.<h4>Methods</h4>Patients with EPM2 ...[more]

PMID: 33773408

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Dataset Information

Italian cohort of Lafora disease: Clinical features, disease evolution, and genotype-phenotype correlations.

Background

Methods

Results

Conclusions

Publications

Italian cohort of Lafora disease: Clinical features, disease evolution, and genotype-phenotype correlations.

Similar Datasets

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