Fetal akinesia: review of the genetics of the neuromuscular causes
- Gianina Ravenscroft1,
- Elliot Sollis1,
- Adrian K Charles2,
- Kathryn N North3,
- Gareth Baynam4,5,
- Nigel G Laing1
- 1Centre for Medical Research, University of Western Australia; Western Australian Institute for Medical Research, Nedlands, Western Australia, Australia
- 2Department of Pediatric Pathology, Princess Margaret Hospital, Perth, Western Australia, Australia
- 3Discipline of Paediatrics and Child Health, Faculty of Medicine, University of Sydney, Institute for Neuroscience and Muscle Research, The Children's Hospital at Westmead, New South Wales, Australia
- 4Genetic Services of Western Australia, King Edward Memorial Hospital, Western Australia, Australia
- 5School of Paediatrics and Child Health, University of Western Australia, Western Australia, Australia
- Correspondence toProfessor Nigel G Laing, Western Australian Institute for Medical Research, Ground Floor, B Block, QEII Medical Centre, Nedlands, Western Australia, 6009, Australia;
Contributors All authors were involved in the synthesis of this review article. GR and ES contributed equally to this manuscript.
- Received 23 May 2011
- Revised 31 July 2011
- Accepted 16 August 2011
- Published Online First 7 October 2011
Fetal akinesia refers to a broad spectrum of disorders in which the unifying feature is a reduction or lack of fetal movement. Fetal akinesias may be caused by defects at any point along the motor system pathway including the central and peripheral nervous system, the neuromuscular junction and the muscle, as well as by restrictive dermopathy or external restriction of the fetus in utero. The fetal akinesias are clinically and genetically heterogeneous, with causative mutations identified to date in a large number of genes encoding disparate parts of the motor system. However, for most patients, the molecular cause remains unidentified. One reason for this is because the tools are only now becoming available to efficiently and affordably identify mutations in a large panel of disease genes. Next-generation sequencing offers the promise, if sufficient cohorts of patients can be assembled, to identify the majority of the remaining genes on a research basis and facilitate efficient clinical molecular diagnosis. The benefits of identifying the causative mutation(s) for each individual patient or family include accurate genetic counselling and the options of prenatal diagnosis or preimplantation genetic diagnosis.
In this review, we summarise known single-gene disorders affecting the spinal cord, peripheral nerves, neuromuscular junction or skeletal muscles that result in fetal akinesia. This audit of these known molecular and pathophysiological mechanisms involved in fetal akinesia provides a basis for improved molecular diagnosis and completing disease gene discovery.
- Gene therapy
- genetic screening/counselling
- neuromuscular disease
- molecular genetics
- muscle disease
- neuromuscular disease
- paediatric oncology
Gianina Ravenscroft and Elliot Sollis contributed equally.
Funding This work was supported by the Australian National Health and Medical Research Council Fellowships 403904 and APP1002147 and project grant 403941.
Competing interests None.
Provenance and peer review Not commissioned; externally peer reviewed.