In fetal akinesia deformation sequence multiple joint contractures (arthrogryposis multiplex congenita) are present due to decreased intrauterine fetal movement. It is an etiologically heterogeneous condition. Causes include underlying abnormalities of the central and peripheral nervous system, of muscle, of connective tissue, intrauterine vascular compromise, maternal disease states, and space constraints within the womb. Although the majority of cases are associated with a low recurrence risk, some cases of fetal akinesia deformation sequence are due to an underlying chromosomal abnormality or mutations in a gene coding for inherited disorders with autosomal dominant, recessive, X-linked or mitochondrial inheritance. For instance, the most common autosomal recessive disorder which can present with fetal akinesia is spinal muscular atrophy due to mutations in the SMN1 gene. So far, OMIM database more strictly refers to fetal akinesia deformation syndrome in regard to mutations in the RAPSN and DOK7 genes (Pena-Shokeir syndrome type I; MIM 208150). Around 50 mutations (including two gross deletions) are described in the DOK7 gene. Some other mutations are reported in the RAPSN gene.
FACTS
References: see text.
FACTS
- The RAPSN gene spans about 15.5kb and includes 8 exons. It is located on 11p11.2-p11.1.
- The DOK7 gene spans about 35.0kb and includes 7 exons. It is located on 4p16.2.
References: see text.
