International retrospective natural history study of LMNA-related congenital muscular dystrophy

Brain Commun. 2021 Apr 11;3(3):fcab075. doi: 10.1093/braincomms/fcab075

Ben Yaou R, Yun P, Dabaj I, Norato G, Donkervoort S, Xiong H, Nascimento A, Maggi L, Sarkozy A, Monges S, Bertoli M, Komaki H, Mayer M, Mercuri E, Zanoteli E, Castiglioni C, Marini-Bettolo C, D’Amico A, Deconinck N, Desguerre I, Erazo-Torricelli R, Gurgel-Giannetti J, Ishiyama A, Kleinsteuber KS, Lagrue E, Laugel V, Mercier S, Messina S, Politano L, Ryan MM, Sabouraud P, Schara U, Siciliano G, Vercelli L, Voit T, Yoon G, Alvarez R, Muntoni F, Pierson TM, Gómez-Andrés D, Reghan Foley A, Quijano-Roy S, Bönnemann CG, Bonne G.

Abstract

Muscular dystrophies due to heterozygous pathogenic variants in LMNA gene cover a broad spectrum of clinical presentations and severity with an age of onset ranging from the neonatal period to adulthood. The authors designed a large international retrospective study of 151 patients affected by muscle laminopathy. Age of onset and age of death were significantly lower in patients who never acquired independent ambulation compared to patients who achieved independent ambulation. The age of ambulation acquisition and age of ambulation loss  were significantly associated with the age of the first respiratory interventions and the first cardiac symptoms. Respiratory and gastrointestinal interventions occurred during first decade while cardiac interventions occurred later. Genotype–phenotype analysis showed that the most common mutation, p.Arg249Trp, was significantly associated with a more severe disease course. This retrospective natural history study of early onset LMNA-related muscular dystrophy confirms the progressive nature of the disorder, initially involving motor symptoms prior to onset of other symptoms (respiratory, orthopaedic, cardiac and gastrointestinal). These categorizations will be important for future clinical trial cohorts. Finally, this study furthers our understanding of the progression of early onset LMNA-related muscular dystrophy and provides important insights into the anticipatory care needs of LMNA-related respiratory and cardiac manifestations.

 

medline link: www.ncbi.nlm.nih.gov/pubmed/27421120#