Rare Pulmonology News

Disease Profile

Fetal akinesia deformation sequence

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

Age of onset

#N/A

ICD-10

#N/A

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

FADS; Fetal akinesia sequence; Pena-Shokeir syndrome, type 1;

Categories

Congenital and Genetic Diseases; Lung Diseases

Summary

Fetal akinesia deformation sequence (FADS) is a condition characterized by decreased fetal movement (fetal akinesia) as well as intra-uterine growth restriction (IUGR), multiple joint contractures (arthrogryposis), facial anomalies, underdevelopment of the lungs (pulmonary hypoplasia) and other developmental abnormalities.[1][2] It is generally accepted that this condition is not a true diagnosis or a specific syndrome, but rather a description of a group of abnormalities resulting from fetal akinesia.[3] About 30% of affected individuals are stillborn; many liveborn infants survive only a short time due to complications of pulmonary hypoplasia.[1] FADS may be inherited in an autosomal recessive manner in some cases and may sometimes be caused by mutations in the RAPSN or DOK7 genes.[4]

Symptoms

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Absent palmar crease
Absent palm lines
0010489
Akinesia
0002304
Arthrogryposis multiplex congenita
0002804
Camptodactyly of finger
Permanent flexion of the finger
0100490
Excessive daytime somnolence
Excessive daytime sleepiness
More than typical sleepiness during day

[ more ]

0001262
Fetal akinesia sequence
0001989
Hypokinesia
Decreased muscle movement
Decreased spontaneous movement
Decreased spontaneous movements

[ more ]

0002375
Intrauterine growth retardation
Prenatal growth deficiency
Prenatal growth retardation

[ more ]

0001511
Micrognathia
Little lower jaw
Small jaw
Small lower jaw

[ more ]

0000347
Multiple joint contractures
0002828
Pulmonary hypoplasia
Small lung
Underdeveloped lung

[ more ]

0002089
Respiratory insufficiency
Respiratory impairment
0002093
30%-79% of people have these symptoms
Cleft palate
Cleft roof of mouth
0000175
Cryptorchidism
Undescended testes
Undescended testis

[ more ]

0000028
Cystic hygroma
0000476
Depressed nasal bridge
Depressed bridge of nose
Flat bridge of nose
Flat nasal bridge
Flat, nasal bridge
Flattened nasal bridge
Low nasal bridge
Low nasal root

[ more ]

0005280
Generalized amyotrophy
Diffuse skeletal muscle wasting
Generalized muscle degeneration
Muscle atrophy, generalized

[ more ]

0003700
Hypertelorism
Wide-set eyes
Widely spaced eyes

[ more ]

0000316
Polyhydramnios
High levels of amniotic fluid
0001561
Posteriorly rotated ears
Ears rotated toward back of head
0000358
Scoliosis
0002650
5%-29% of people have these symptoms
Dandy-Walker malformation
0001305
Intestinal hypoplasia
Underdeveloped instestine
0005245
Pterygium
0001059
1%-4% of people have these symptoms
Stillbirth
Stillborn
0003826
Percent of people who have these symptoms is not available through HPO
Abnormal abdomen morphology
Abnormality of abdomen structure
0001438
Abnormality of pelvic girdle bone morphology
Abnormal shape of pelvic girdle bone
0002644
Absent septum pellucidum
0001331
Autosomal recessive inheritance
0000007
Blepharophimosis
Narrow opening between the eyelids
0000581
Cavum septum pellucidum
0002389
Cerebellar hypoplasia
Small cerebellum
Underdeveloped cerebellum

[ more ]

0001321
Depressed nasal tip
Caved in nasal tip
Depressed tip of nose
Flat nasal tip
Flat tip of nose
Flattened nasal tip
Nasal tip, depressed

[ more ]

0000437
Elbow ankylosis
0003070
High palate
Elevated palate
Increased palatal height

[ more ]

0000218
High, narrow palate
Narrow, high-arched roof of mouth
Narrow, highly arched roof of mouth

[ more ]

0002705
Hydrocephalus
Too much cerebrospinal fluid in the brain
0000238
Long philtrum
0000343
Narrow mouth
Small mouth
0000160
Premature birth
Premature delivery of affected infants
Preterm delivery

[ more ]

0001622
Proptosis
Bulging eye
Eyeballs bulging out
Prominent eyes
Prominent globes
Protruding eyes

[ more ]

0000520
Ptosis
Drooping upper eyelid
0000508
Rocker bottom foot
Rocker bottom feet
Rocker-bottom feet
Rockerbottom feet

[ more ]

0001838
Short neck
Decreased length of neck
0000470
Short palpebral fissure
Short opening between the eyelids
0012745
Short umbilical cord
0001196
Slender long bone
Long bones slender
Thin long bones

[ more ]

0003100
Small for gestational age
Birth weight less than 10th percentile
Low birth weight

[ more ]

0001518
Small placenta
0006266
Talipes equinovarus
Club feet
Club foot
Clubfeet
Clubfoot

[ more ]

0001762
Telecanthus
Corners of eye widely separated
0000506
Thin ribs
Slender ribs
0000883
Thoracic hypoplasia
Small chest
Small thorax

[ more ]

0005257
Ulnar deviation of the hand
0009487
Ulnar deviation of the hand or of fingers of the hand
0001193

Cause

Many underlying causes of fetal akinesia deformation sequence (FADS) have been recognized including genetic, environmental and maternal factors.[2] The features of the condition are largely due to decreased fetal activity/movement.[2] 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.[1]

Possible causes for decreased fetal movement which may contribute to the features of FADS may include:[2]

  • 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]

Diagnosis

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.

Treatment

The resources below provide information about treatment options for this condition. If you have questions about which treatment is right for you, talk to your healthcare professional.

Management Guidelines

  • Project OrphanAnesthesia is a project whose aim is to create peer-reviewed, readily accessible guidelines for patients with rare diseases and for the anesthesiologists caring for them. The project is a collaborative effort of the German Society of Anesthesiology and Intensive Care, Orphanet, the European Society of Pediatric Anesthesia, anesthetists and rare disease experts with the aim to contribute to patient safety.

Learn more

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

In-Depth Information

  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
  • PubMed is a searchable database of medical literature and lists journal articles that discuss Fetal akinesia deformation sequence. Click on the link to view a sample search on this topic.

References

  1. Fetal akinesia deformation sequence. Orphanet. July 2005; https://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=EN&Expert=994. Accessed 10/2/2012.
  2. JG Hall. Pena-Shokeir phenotype (fetal akinesia deformation sequence) revisited. Birth Defects Res A Clin Mol Teratol. August 2009; 85(8):677-694.
  3. 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.
  4. Fetal Akinesia Deformation Sequence; FADS. Online Mendelian Inheritance in Man (OMIM). April 2010; https://www.ncbi.nlm.nih.gov/omim/208150. Accessed 6/29/2011.

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