LAMA2-Related Muscular Dystrophy: The Importance of Accurate Phenotyping and Brain Imaging in the Diagnosis of LGMD

Article type: Case Report

Authors: Stojkovic, Tanya^{a; b; *} | Masingue, Marion^a | Métay, Corinne^{b; c} | Romero, Norma B.^{b; d} | Eymard, Bruno^a | Ben Yaou, Rabah^b | Rialland, Laetitia^c | Drunat, Séverine^e | Gartioux, Corine^b | Nelson, Isabelle^b | Allamand, Valérie^b | Bonne, Gisèle^b | Villar-Quiles, Rocio Nur^{a; b}

Affiliations: [a] APHP, Reference Center for Neuromuscular Disorders, Institut de Myologie, Pitié-Salpêtrière Hospital, Paris, France | [b] INSERM, Institut de Myologie, Centre de Recherche en Myologie, Sorbonne Université, Paris, France | [c] AP-HP, Centre de Génétique Moléculaire et Chromosomique, UF Cardiomyogénétique et Myogénétique Moléculaire et Cellulaire, Pitié-Salpêtrière Hospital, Paris, France | [d] Neuromuscular Morphology Unit, Institut de Myologie, APHP, Pitié-Salpêtrière Hospital, Paris, France | [e] Département de génétique, Hôpital Universitaire Robert Debré, Paris, France

Correspondence: [*] Correspondence to: Dr Tanya Stojkovic, Centre de Référence des maladies neuromusculaires Nord / Est / Ile-de-France, Groupe Hospitalier Pitié-Salpêtrière, 47-83 boulevard de l’Hôpital, 75651 Paris Cedex 13, France. E-mail: tanya.stojkovic@aphp.fr.

Abstract: We report three siblings from a non-consanguineous family presenting with contractural limb-girdle phenotype with intrafamilial variability. Muscle MRI showed posterior thigh and quadriceps involvement with a sandwich-like sign. Whole-exome sequencing identified two compound heterozygous missense TTN variants and one heterozygous LAMA2 variant. Brain MRI performed because of concentration difficulties in one of the siblings evidenced white-matter abnormalities, subsequently found in the others. The genetic analysis was re-oriented, revealing a novel pathogenic intronic LAMA2 variant which confirmed the LAMA2-RD diagnosis. This work highlights the importance of a thorough clinical phenotyping and the importance of brain imaging, in order to orientate and interpret the genetic analysis.

Keywords: Limb-girdle muscular dystrophy, LAMA2, white matter, brain MRI, laminin-211

DOI: 10.3233/JND-221555

Journal: Journal of Neuromuscular Diseases, vol. 10, no. 1, pp. 125-133, 2023