Infantile facioscapulohumeral muscular dystrophy revisited: Expansion of clinical phenotypes in patients with a very short EcoRI fragment Tai-Heng Chen a,b , Yu-Hung Lai c,d , Pei-Lun Lee b , Jong-Hau Hsu b,d , Kanako Goto e , Yukiko K. Hayashi e,f , Ichizo Nishino e,f , Chin-Wen Lin g , Hsiang-Hung Shih b , Chao-Ching Huang h , Wen-Chen Liang b , Wen-Fu Wang i,j,⇑ , Yuh-Jyh Jong b,d,g,⇑ a Division of Pediatric Emergency, Department of Emergency, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan b Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan c Department of Ophthalmology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan d Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan e Department of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan f Department of Clinical Development, Translational Medical Center, National Center of Neurology and Psychiatry, Tokyo, Japan g Department of Laboratory Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan h Department of Pediatrics, National Cheng Kung University Hospital, Tainan, Taiwan i Department of Neurology, Changhua Christian Hospital, Changhua, Taiwan j Center for General Education, Central Taiwan University of Science and Technology, Taichung, Taiwan Received 1 August 2012; received in revised form 25 December 2012; accepted 7 January 2013 Abstract Contrary to the classical form, infantile facioscapulohumeral muscular dystrophy (FSHD) usually denotes a severe phenotype and is frequently associated with extramuscular involvements. To elucidate the genotype–phenotype correlation in this severe subgroup, we identified a cohort of nine patients with infantile FSHD who also carried a very short (10–13 kb) EcoRI fragment. Their current age ranged from 8 to 33 years and age of onset ranged from 0.4 to 5 years. One patient even manifested his first FSHD-related symptoms at as early as 5 months of age, including inability to smile, poor response to call, and infantile spasms. To date, four patients were wheelchair-bound and six patients had asymmetric weakness. Sensorineural hearing loss and abnormal fundoscopic findings were observed in eight and all of patients respectively. Three with the smallest EcoRI fragments (10–11 kb, with normal length being 50–300 kb) had mental retardation. Two of these had epilepsy. Cardiac arrhythmias were found in five patients. Restrictive ventilatory defects were observed in seven patients, with one progressing to chronic respiratory failure. Two had swallowing difficulties; one of these required gastrostomy. We identified several rarely reported phenotypes in infantile FSHD, including cardiac arrhythmia, respiratory insufficiency, and swallowing difficulties. There seems to be a correlation between the severity of phenotype and the very short EcoRI fragment in the chromosome 4q35 region. We conclude that the high frequency of multi-organ involvements in this severe FSHD variant suggests the need for an early and multidisciplinary intervention. Ó 2013 Elsevier B.V. All rights reserved. Keywords: Infantile onset; Facioscapulohumeral muscular dystrophy; EcoRI fragment; Cardiac conductive defect; Restrictive ventilatory defect 1. Introduction With a worldwide prevalence of 1 in 15,000–20,000, facioscapulohumeral muscular dystrophy (FSHD; MIM158900) accounts for the third most common form of muscular dystrophy [1]. In the majority of patients, 0960-8966/$ - see front matter Ó 2013 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.nmd.2013.01.005 ⇑ Corresponding author. Address: Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, No. 100, Shih-Chuan 1st Road, Kaohsiung 80708, Taiwan. Tel.: +886 7 311 7820; fax: +886 7 321 2062, Department of Neurology, Changhua Christian Hospital, No. 135, Nanxiao St., Changhua City, Changhua County 500, Taiwan. Tel.: +886 4 723 8595; fax: +886 4 7232942. E-mail addresses: 68251@cch.org.tw (W.-F. Wang), yjjong@kmu. edu.tw (Y.-J. Jong). www.elsevier.com/locate/nmd Available online at www.sciencedirect.com Neuromuscular Disorders xxx (2013) xxx–xxx ARTICLE IN PRESS Please cite this article in press as: Chen T-H et al., Infantile facioscapulohumeral muscular dystrophy revisited: Expansion of clinical phenotypes in pa- tients with a very short EcoRI fragment, Neuromuscul Disord (2013), http://dx.doi.org/10.1016/j.nmd.2013.01.005