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Genetic and Rare Diseases Information Center (GARD)

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Fetal akinesia deformation sequence

Other Names for this Disease
  • Arthrogryposis multiplex congenita with pulmonary hypoplasia
  • FADS
  • Fetal akinesia sequence
  • Pena-Shokeir syndrome, type 1
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Your Question

I've had three consecutive cases of Pena-Shokeir. Is there any kind of test available that can assure me an unaffected pregnancy? Are the genes detectable? What are the genes involved and how can I get them tested?

Our Answer

We have identified the following information that we hope you find helpful. If you still have questions, please contact us.

What causes fetal akinesia deformation sequence (FADS)?

Many underlying causes of fetal akinesia deformation sequence (FADS) have been recognized including genetic, environmental and maternal factors.[1] The features of the condition are largely due to decreased fetal activity/movement.[1] Failure of normal swallowing results in polyhydramnios (too much amniotic fluid), and lack of movement of the diaphragm and intercostal muscles leads to pulmonary hypoplasia (underdevelopment of the lungs). Lack of normal fetal movement also results in a short umbilical cord and multiple joint contractures.[2]

Possible causes for decreased fetal movement which may contribute to the features of FADS may include:[1]
  • Neurologic abnormalities such as cerebral and cerebellar dysgenesis (abnormal development); spinal tract, myelin, and end plate disturbances; and ischemia (deficient blood supply) with secondary loss of neuron function
  • Myopathic (muscle-related) abnormalities such as dystrophies and dyplasias
  • Connective tissue abnormalities including chondrodysplasias, restrictive skin, and joint limitation or laxity
  • Fetal edema for a variety of reasons (storage, metabolic, heart failure, lymphatic dysplasia, etc.)
  • Maternal illness, drugs, and antibodies (including maternal myasthenia gravis)
  • Ischemic changes during embryonic/fetal development, which may be due to developmental vascular abnormalities, trauma, hypotension, drugs, infections, and maternal illness or thrombophilia

Autosomal recessive inheritance of FADS has been implied in several published cases.[3] Genes in which mutations have been detected in affected individuals include the RAPSN and DOK7 genes.[4] According to current literature, the recurrence risk is estimated to be 10–25%.[3]

Last updated: 10/3/2012

Is genetic testing available for fetal akinesia deformation sequence?

There are quite a few potential underlying causes of fetal akinesia deformation sequence (FADS). Sometimes the cause is unknown, sometimes the cause is known and is not genetic, and other times although a genetic cause may be suspected, genetic testing may not be available. Currently, genetic testing is available for two genes in which mutations have reportedly caused the condition in specific cases.

GeneTests lists the names of the laboratories that are performing genetic testing for FADS. To view the contact information for these laboratories, click on the following links:
DOK7-Related Fetal Akinesia Deformation Sequence
RAPSN-Related Fetal Akinesia Deformation Sequence

Please note that most of the laboratories listed through GeneTests do not accept direct contact from patients and their families; therefore, if you are interested in learning more, you will need to work with a health care provider or a genetics professional.
Last updated: 10/3/2012

What are some future pregnancy options after having a pregnancy affected with fetal akinesia deformation sequence (FADS)?

Consideration of genetic counseling is recommended for individuals who have a family history of FADS. The risk of recurrence largely depends on the underlying cause of the condition in the family, if it is known. According to current literature, the recurrence risk is estimated to be 10–25%.[3]

In most cases, prenatal diagnosis for FADS relies on ultrasound during the pregnancy, which may reveal some of the characteristic features of the condition.[2] It has been reported that ultrasound diagnosis of FADS is feasible from 14 weeks of gestation onwards, although it has been reported as early as 12 weeks.[3][1] In some cases, specific features might only become evident in later ultrasounds.[3]

Because the underlying cause of FADS in many cases is unknown, and/or genetic testing is not always available or informative, ensuring an unaffected pregnancy is often not possible. Preimplantation genetic diagnosis (PGD) for a genetic condition is an option when a specific genetic cause for the condition has been identified and genetic testing is available. If a particular case of FADS is known to be due to a specific genetic abnormality (FADS may be associated with a variety of conditions) and the above conditions are met, PGD for the condition associated with FADS may be possible. A genetics professional can help determine if this is an option on a case-by-case basis.

Likewise, if a genetic cause for FADS has been identified and the causative mutations in a family are known, prenatal diagnosis during the pregnancy via chorionic villus sampling (CVS) or amniocentesis may also be possible.

Individuals seeking information about their specific preconception and prenatal options should speak with a genetics professional.
Last updated: 10/5/2012

How can I find a genetics professional in my area?

Genetics clinics are a source of information for individuals and families regarding genetic conditions, treatment, inheritance, and genetic risks to other family members. More information about genetic consultations is available from Genetics Home Reference. To find a genetics clinic, we recommend that you contact your primary healthcare provider for a referral.

The following online resources can help you find a genetics professional in your community:
Last updated: 10/18/2013

  • JG Hall. Pena-Shokeir phenotype (fetal akinesia deformation sequence) revisited. Birth Defects Res A Clin Mol Teratol. August 2009; 85(8):677-694.
  • Fetal akinesia deformation sequence. Orphanet. July 2005; Accessed 10/2/2012.
  • F Hoellen et al. Arthrogryposis multiplex congenita and Pena-Shokeir phenotype: challenge of prenatal diagnosis--report of 21 cases, antenatal findings and review. Fetal Diagn Ther. 2011; 30(4):289-298.
  • Fetal Akinesia Deformation Sequence; FADS. Online Mendelian Inheritance in Man (OMIM). April 2010; Accessed 6/29/2011.