Cataract, abnormal electroretinogram and visual evoked potentials in a child with SMA-LED2 - extending the phenotype

Article type: Case Report

Authors: Oliwa, Agata^{a; *} | Joseph, Shuko^b | Millar, Eoghan^c | Horrocks, Iain^b | Penman, Dawn^d | Baptista, Julia^e | Cullup, Thomas^f | Constantinou, Panayiotis^g | Heuchan, Anne-Marie^h | Hamilton, Ruthⁱ | Longman, Cheryl^g

Affiliations: [a] Undergraduate Medical School, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK | [b] Fraser of Allander Neurosciences Unit, Royal Hospital for Children, Glasgow, UK | [c] Department of Ophthalmology, Royal Hospital for Children, Glasgow, UK | [d] Department of Pathology, Queen Elizabeth University Hospital, Glasgow, UK | [e] Peninsula Medical School, Faculty of Heath, University of Plymouth, Plymouth, UK | [f] North Thames Genomic Laboratory Hub, Great Ormond Street Hospital NHS Foundation Trust, London, UK | [g] West of Scotland Regional Genetics Service, Queen Elizabeth University Hospital, Glasgow, UK | [h] Department of Neonatology, Royal Hospital for Children, Glasgow, UK | [i] Department of Clinical Physics and Bioengineering, Royal Hospital for Children, NHS Greater Glasgow & Clyde, Glasgow, UK

Correspondence: [*] Correspondence to: Agata Oliwa, Undergraduate Medical School, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, G12 8QQ, UK. Tel.: +44 141 330 5921; E-mail: [email protected]; E-mail: [email protected].

Abstract: This case report describes a girl who presented antenatal arthrogryposis and postnatal hypotonia, generalized and respiratory weakness, joint deformities particularly affecting the lower limbs and poor swallow. By 5 months, cataracts, abnormal electroretinograms, visual evoked potentials (VEPs) and global developmental impairments were recognized. No causative variants were identified on targeted gene panels. After her unexpected death at 11 months, gene-agnostic trio whole exome sequencing revealed a likely pathogenic de novo BICD2 missense variant, NM_001003800.1, c.593T>C, p.(Leu198Pro), confirming the diagnosis of spinal muscular atrophy lower extremity predominant type 2 (SMA-LED2). We propose that cataract, abnormal electroretinograms and VEPs are novel features of SMA-LED2.

Keywords: Arthrogryposis, cataract, BICD2, SMA-LED2, spinal muscular atrophy lower extremity predominant

DOI: 10.3233/JND-220818

Journal: Journal of Neuromuscular Diseases, vol. 9, no. 6, pp. 803-808, 2022