Not so lethal congenital contractures: two adult cases of Lethal Congenital Contracture Syndrome Type 11

• Published in: Journal of neurology, neurosurgery and psychiatry Vol. 94; no. Suppl 1; p. A87
• Main Authors: Emma, Dolan, Oisin, Friel, Gerard, Mullane, Ciara, Kehoe, Grainne, Mulkerrin, James, O’Rourke, Anna, Whelehan, Shane, Smyth, Stela, Lefter, Eavan, McGovern
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group Ltd 28.11.2023; BMJ Publishing Group LTD
• Subjects: Association of British Neurologists: Annual Meeting Abstracts 2023; Mutation; Scoliosis
• ISSN: 0022-3050; 1468-330X
• DOI: 10.1136/JNNP-2023-ABN.268

Case DescriptionWe present two cases of lethal congenital contracture syndrome type 11 (LCCS11) surviving into adulthood.Case one is a 22-year old female who presented acutely in type-two respiratory failure requiring intuba- tion. The patient had reduced BMI (12.6kg/m2), an elongated face, microstomia, distal upper/lower limb joint contractures, and scoliosis.Prior genetic workup revealed a paternally-inherited missense mutation in GLDN (c.1494G>C, p.Le- u498Phe). Chromosomal microarray analysis identified a maternal deletion of GLDN, which combined with the missense mutation, confirmed LCCS11.Case two is a 25-year-old lady who presented to outpatient services. The patient had multiple joint con- tractures and marked scoliosis. Whole exome sequencing revealed a homozygous frameshift pathogenic mutation in the GLDN gene (c.980_981del, p.Ser327CysfsTer2), diagnosing LCCS11.DiscussionGLDN encodes the gliomedin protein, required for formation of the nodes of Ranvier and PNS development. (1 2 3) Biallelic variants in GLDN are associated with LCCS11, a typically lethal form of arthrogryposis multiplex congenita, characterised by joint contractures and limited foetal movements.LCCS11 was described as invariably lethal when first reported (1). Recent studies, have highlighted higher survival rates than initially described (2). Our two cases expand the phenotypic spectrum; one presenting with respiratory decompensation, the second presenting with multiple joint contractures.