“Confounding Contractures” A Non-Lethal Presentation of a Lethal Disorder (P11-9.010)

Abstract

<h3>Objective:</h3> N/A <h3>Background:</h3> The arthrogryposes are a group of non-progressive conditions characterised by multiple joint contractures at birth. They are a heterogenous group of disorders with multiple neurogenic, myopathic and connective tissue aetiologies. The Lethal Congenital Contracture Syndromes (LCCS) are a rare cause of arthrogryposis and are associated with significant perinatal pulmonary abnormalities such as pulmonary hypolasia and high mortality in the neonatal period. <h3>Design/Methods:</h3> We report the case of a 25 year old female who presented at birth with multiple lower limb contractures, bilateral talipes and hip fractures/dislocations. There was no evidence of any cardiorespiratory compromise in the neonatal period. The patient’s early life was dominated by extensive orthopaedic interventions for lower limb contractures and scoliosis, but she had an otherwise unremarkable development with no evidence of cardiac or pulmonary complications and no evidence of intellectual disability. There was a history of an early neonatal death in a brother with a similar phenotype, however no underlying cause was established. Examination demonstrated areflexia but no discernible weakness. <h3>Results:</h3> A muscle biopsy at 3 months showed non-specific myopathic features, but was normal on repeat biopsy aged 21. EMG showed subtle chronic myopathic features. Targeted genetic analysis with congenital myopathy and arthrogryposis panel was unrevealing. Proceeding to whole exome sequencing revealed a homozygous pathogenic variant in the GLDN gene, confirming the diagnosis of Lethal Congenital Contracture Syndrome type 11. <h3>Conclusions:</h3> Despite the diagnosis, which is commonly fatal in the neonatal period, the patient has survived well into adulthood and functioning at a high level independently with no evidence of any pulmonary complications. This highlights a previously unreported case of an adult patient with LCCS 11 without evidence of respiratory compromise, while also highlighting the value of broad genetic testing in this cohort. <b>Disclosure:</b> Dr. Mullane has nothing to disclose. Dr. Donlon has nothing to disclose. Dr. Smyth has nothing to disclose.