Autism and heritable bone fragility: A true association?

OBJECTIVES: Osteogenesis Imperfecta (OI) is a heterogeneous condition mainly characterised by bone fragility; intelligence is reported to be normal. However, a minority of children seen also show symptomology consistent with an 'Autism Spectrum Disorder'. A joint genetics and psychology research study was undertaken to identify these patients using 'Gold Standard' research tools: Autism Diagnostic Inventory Revised (ADI-R); Autism Diagnostic Observation Schedule (ADOS) and undertake genetic analyses in them. METHOD: = 7 children with autistic traits and severe/complex OI were recruited to the study. The study was set-up to explore whether there was a genetic link between bone fragility and autism in a sub-set of patients with bone fragility identified with autism traits in our complex/severe OI clinic. This was not set-up as a prevalence study but rather an exploration of genetics in association with ADI/ADOS confirmed ASD and bone fragility. ADI ADI comprises a 93 item semi-structured clinical review with a diagnostic algorithm diagnosing Autism; ADOS is a semi-structured assessment of socialisation, communication and play/imagination which also provides a diagnostic algorithm. EXOME SEQUENCING: In patients recruited, those that fulfilled research criteria for diagnosis of autism using above tools were recruited to trio whole exome sequencing (WES). RESULTS: . CONCLUSIONS: Although, not set out as an objective, we were able to establish that identifying autism had important clinical and social benefits for patients and their families in ensuring access to services, appropriate schooling, increased understanding of behaviour and support. LAY SUMMARY: It is important for clinicians looking after children with brittle bone disease, also referred to as Osteogenesis Imperfecta (OI) to be aware of early features of developmental delay/autistic traits especially with severe forms of OI as the emphasis is on their mobility and bone health. Ensuring appropriate assessment and access to services early-on will enable these patients to achieve their potential. Further investigations of genomics in bone fragility in relation to autism are required and dual diagnosis is essential for high quality clinical and educational provision.