Case Report A Rare Case of Severe Congenital RYR1-Associated Myopathy Nicola Laforgia , 1 Manuela Capozza, 1 Lucrezia De Cosmo, 1 Antonio Di Mauro , 1 Maria Elisabetta Baldassarre, 1 Francesca Mercadante, 2 Anna Laura Torella, 3 Vincenzo Nigro, 3 and Nicoletta Resta 2 1 Neonatology and Neonatal Intensive Care Unit, Department of Biomedical Science and Human Oncology, “Aldo Moro” University of Bari, Policlinico Hospital, Piazza Giulio Cesare n. 11, 70124 Bari, Italy 2 Medical Genetics Unit, Department of Biomedical Sciences and Human Oncology, “Aldo Moro” University of Bari, Policlinico Hospital, Piazza Giulio Cesare n. 11, 70124 Bari, Italy 3 Medical Genetics Laboratory, Department of Precision Medicine, “L.Vanvitelli” University of Campania, Telethon Institute of Genetics and Medicine (TIGEM), Naples, Italy Correspondence should be addressed to Nicola Laforgia; nicola.laforgia@uniba.it Received 12 February 2018; Revised 28 June 2018; Accepted 19 July 2018; Published 1 August 2018 Academic Editor: Balraj Mittal Copyright © 2018 Nicola Laforgia et al. is is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Congenital myopathies are a group of rare inherited diseases, defined by hypotonia and muscle weakness. We report clinical and genetic characteristics of a male preterm newborn, whose phenotype was characterized by severe hypotonia and hyporeactivity, serious respiratory distress syndrome that required mechanical ventilation, clubfoot, and other dysmorphic features. e diagnostic procedure was completed with the complete exome sequencing of the proband and of his parents and his sister, which showed new mutations in the ryanodine receptor gene (RYR1), which maps to chromosome 19q13.2 and encodes the skeletal muscle isoform of a calcium-release channel in the sarcoplasmic reticulum (RyR1). is report confirms that early diagnosis and accurate study of genomic disorders are very important, enabling proper genetic counselling of the reproductive risk, as well as disease prognosis and patient management. 1. Introduction Congenital myopathies are a group of rare inherited diseases, defined by hypotonia and muscle weakness, that usually present at birth or early childhood, in association with characteristic morphological defects. ey are caused by genetic mutations of the structural proteins of skeletal muscle and present variable inheritance: dominant, recessive, or X- linked [1, 2]. Mutations in a single gene may be associated with different clinical and histological findings, and the same clinical or histological conditions may be due to mutations in different genes [3]. Phenotypic findings include severe neonatal-onset, mild forms with nonprogressive weakness, and muscle hypotonia with later onset. e old classification of congenital myopathies was mainly based on histological features observed in the muscle biopsy [1, 3]: myopathies with “rods” (nemaline myopathies), myopathies with centralized nuclei (myotubular and cen- tronuclear myopathies), myopathies with fiber type dispro- portion, and myopathies with “cores” (oval areas in the muscle cells) [4, 5]. e last ones are the most common forms of congenital myopathies, in particular the “central core” myopathy (CCD). e most known CCD is the autosomal dominant inherited form caused by mutations localized in three hot spots in the ryanodine receptor 1 gene (RYR1), asso- ciated with malignant hyperthermia susceptibility (MHS) and clinically characterized by minor hypotonia and nonpro- gressive weakness. Recessive mutations are located through- out the entire RYR1 gene and characterized by a more severe and progressive clinical presentation with neonatal-onset and significant generalized muscle weakness [6–8] . Commoner myopathy disorders presenting in fetal or neonatal period are shown in Table 1. Hindawi Case Reports in Genetics Volume 2018, Article ID 6184185, 7 pages https://doi.org/10.1155/2018/6184185