P31 Arthritis: a previously unrecognised feature of KBG syndrome

Abstract

Background: With around 100 reported cases, KBG syndrome is a rare genetic condition characterised by developmental delay, dysmorphic features, macrodontia and skeletal anomalies. Arthritis has not previously been described in individuals with KBG syndrome. Methods: We performed a retrospective case note review. Results: A 17 year old girl, initially presented aged 20 months with bilaterally swollen knees and elbow stiffness. She had a background of global developmental delay with significant behavioural issues. Examination elicited bilateral knee flexion contractures and left wrist pain. Initial management included non-steroidal anti-inflammatories, physiotherapy and splints. Subsequently, she developed wrist and 3rd proximal interphalangeal (PIP) joint restriction. She had relative short stature (9-25th centile) and dysmorphic features; prominent forehead, hypertelorism, brachydactyly, 5th finger clinodactyly and right single palmar crease. Paediatric psychiatry assessment was requested aged four, due to her unusual behaviour and social interaction, who diagnosed an atypical autistic disorder. By age six, on initial paediatric rheumatology review, her joint symptoms had progressed. Clinical examination confirmed inflammatory polyarthritis especially wrists, knees, ankles and PIP joints. She had short-lived benefit from multiple intra-articular joint injections. She had partial response to methotrexate but stopped this due to intolerance. She had various biological therapies all with limited response; etanercept for six months aged 10, infliximab for eight months aged 12 stopped after an infusion reaction, tocilizumab for 18 months from age 13 stopped as it was ineffective. She has now been on abatacept for four years with reasonable control of her arthritis. She developed increasing back pain and stiffness with unusual radiographic appearances: elongated vertebral bodies on Xray and MRI with endplate changes and loss of anterior vertebral body height. She subsequently developed dystrophic toe nails. Aged 14 years she developed seizures. She had an extensive genetic and metabolic diagnostic work-up including normal karyotype, normal organic and amino acids. Possible diagnoses including Rett's syndrome, Smith Magenic syndrome and mucopolysaccharidoses were excluded. Chronic infantile neurological cutaneous and articular syndrome (CINCA) was considered but clinical picture and investigations were not thought to be consistent and no NLRP3 mutation was identified. At age 14, a genetic mutation in ANKRD11 gene was identified, diagnostic of KBG syndrome. KBG is an autosomal dominant condition caused by mutations in ANKRD11 at 16q24.3, which has an essential role in controlling acetylation and gene expression during nervous system development. Phenotype typically includes learning difficulties, macrodontia, seizures, feeding difficulties and autism. Recognised skeletal features include short stature, costovertebral abnormalities, clinodactyly, but to our knowledge there are no previous descriptions of inflammatory arthritis as a feature. Conclusion: We describe a case of KBG syndrome with arthritis a key feature. We suggest consideration of this diagnosis in children presenting with arthritis in the context of developmental delay and learning difficulties and other characteristic features.