Genetics of neuromuscular fetal akinesia in the genomics era

J Med Genet. 2018 Aug;55(8):505-514. doi: 10.1136/jmedgenet-2018-105266. Epub 2018 Jun 29.


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.

Keywords: clinical genetics; developmental; diagnostics tests; molecular genetics; neuromuscular disease.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Arthrogryposis / diagnosis
  • Arthrogryposis / genetics*
  • Arthrogryposis / mortality
  • Biomarkers
  • Cell Differentiation / genetics
  • Gene Expression Regulation
  • Genetic Association Studies* / methods
  • Genetic Predisposition to Disease*
  • Genomics* / methods
  • Humans
  • Motor Neurons / cytology
  • Motor Neurons / metabolism
  • Nervous System Diseases / diagnosis
  • Nervous System Diseases / genetics
  • Nervous System Diseases / metabolism
  • Neuromuscular Junction / genetics
  • Neuromuscular Junction / metabolism


  • Biomarkers

Supplementary concepts

  • Pena Shokeir syndrome, type 1