Muscular, Ocular and Brain Involvement Associated with a De Novo 11q13.2q14.1 Duplication: Contribution to the Differential Diagnosis of Muscle-Eye-Brain Congenital Muscular Dystrophy

Article type: Case Report

Authors: Villar-Quiles, Rocío N.^{a; *} | Gomez-Garcia de la Banda, Marta^b | Barois, Annie^b | Bouchet-Séraphin, Celine^c | Romero, Norma B.^{d; e} | Rio, Marlène^f | Quijano-Roy, Susana^{b; g} | Ferreiro, Ana^{a; d}

Affiliations: [a] Basic and Translational Myology Laboratory, Unité de Biologie Fonctionnelle et Adaptative (BFA), UMR 8251, CNRS/ Université de Paris, Paris, France | [b] Neuromuscular Disorders Unit, Pediatric Neurology and Intensive Care Department, CHU Paris IdF Ouest, Hôpital Raymond Poincaré (APHP), Garches, France | [c] Département de Génétique, Hôpital Bichat Claude Bernard (APHP), Paris, France | [d] Centre de Référence de Pathologie Neuromusculaire Nord/Est/Ile-de-France (APHP), Institut de Myologie, GH Pitié-Salpêtrière, Paris, France | [e] Centre de Référence de Pathologie Neuromusculaire Nord/Est/Ile-de-France (APHP), Institut de Myologie, Laboratoire de Pathologie Risler, GH Pitié-Salpêtrière, Paris, France | [f] Departments of Pediatrics, Neurology and Genetics, Hôpital Necker-Enfants-Malades (APHP), Paris, France | [g] Paris Saclay Universities, UVSQ University of Versailles, UMR 1179 INSERM, Garches, France

Correspondence: [*] Correspondence to: Villar-Quiles Rocío N, Basic and Translational Myology Lab, Unité de Biologie Fonctionnelle et Adaptative (BFA), UMR 8251 Université de Paris-CNRS, Bâtiment Lamarck, 5 Rue Marie-Andrée Lagroua Weill-Hallé, 75205 Paris cedex 13, France. Tel.: +33 1 57277959; Fax: +33 1 57277953; E-mail: rocionur@gmail.com.

Abstract: Muscular weakness and hypotonia may be associated with multisystem involvement giving rise to complex phenotypes, many of which are uncharacterized. We report a patient presenting with congenital hypotonia and severe ocular and brain abnormalities, evoking a Muscle Eye Brain disease (MEB). She had global muscular weakness, hypotonia and amyotrophy, joint hyperlaxity, kyphoscoliosis, respiratory insufficiency, dysmorphic features and severe intellectual disability. Brain MRI showed cortical atrophy and hypoplasia of the corpus callosum. Normal CK levels, non-progressive course and absence of dystrophic features or α-dystroglycan abnormalities on the muscle biopsy were not typical of MEB. CGH array identified a large de novo duplication in chromosome 11, including regions partially duplicated in three other patients with common clinical features. This report adds to the differential diagnosis of complex phenotypes characterized by muscular, ocular and CNS involvement and highlights the potential contribution of still unrecognized chromosomal abnormalities to these phenotypes.

Keywords: Myopathy, ocular involvement, congenital muscular dystrophy, muscle-eye-brain, dystroglycanopathy;, CNV

DOI: 10.3233/JND-190413

Journal: Journal of Neuromuscular Diseases, vol. 7, no. 1, pp. 69-76, 2020