Fetal hypokinesia or akinesia encompasses a broad spectrum of disorders, united by impaired movement in utero. Often, the underlying aetiology is genetic in origin, affecting part of the neuromuscular system. The affordable and high-throughput nature of next-generation DNA sequencing has led to an explosion in disease gene discovery across rare diseases, including fetal akinesias. A genetic diagnosis has clinical utility as it may affect management and prognosis and informs recurrence risk, facilitating family planning decisions. More broadly, knowledge of disease genes increasingly allows population-based preconception carrier screening, which has reduced the incidence of recessive diseases in several populations. Despite gains in knowledge of the genetics of fetal akinesia, many families lack a genetic diagnosis. In this review, we describe the developments in Mendelian genetics of neuromuscular fetal akinesia in the genomics era. We examine genetic diagnoses with neuromuscular causes, specifically including the lower motor neuron, peripheral nerve, neuromuscular junction and muscle.
- diagnostics tests
- molecular genetics
- neuromuscular disease
- clinical genetics
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SJB and ML contributed equally.
Contributors SJB and ML cowrote the manuscript. SJB edited and formatted the manuscript. DM and AC edited the manuscript and added clinical insight. CML edited the manuscript and provided pathological insight. MD edited the manuscript and provided diagnostic genomics insight. NGL and GR conceptualised the paper and edited the manuscript.
Funding SJB is supported by The Fred Liuzzi Foundation (Australia). NGL (APP1117510) and GR (APP1122952) are supported by the Australian NHMRC. GR is also supported by the Department of Health FutureHealth WA Merit Awards. This work is funded by The Fred Liuzzi Foundation, Association Francaise contre les Myopathies (AFM) (18724) and NHMRC (APP1080587). The funding agencies had no involvement in the design, completion or writing of this study.
Competing interests None declared.
Patient consent Not required.
Provenance and peer review Not commissioned; externally peer reviewed.
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