Fetal Akinesia Deformation Sequence (FADS)/Lethal Multiple Pterygium Syndrome Panel

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy Genes Gene CPT Codes Copy CPT Codes
10291 CHRNA1 81479,81479 Order Options and Pricing
CHRND 81479,81479
CHRNE 81479,81479
CHRNG 81479,81479
CNTN1 81479,81479
COLQ 81479,81479
DOK7 81479,81479
GLE1 81479,81479
KLHL40 81479,81479
MUSK 81479,81479
RAPSN 81479,81479
Test Code Test Copy Genes Panel CPT Code Gene CPT Codes Copy CPT Code Base Price
10291Genes x (11)81479 81479 $890 Order Options and Pricing

Pricing Comments

We are happy to accommodate requests for testing single genes in this panel or a subset of these genes. The price will remain the list price. If desired, free reflex testing to remaining genes on panel is available. Alternatively, a single gene or subset of genes can also be ordered via our PGxome Custom Panel tool.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

For Reflex to PGxome pricing click here.

Turnaround Time

18 days on average for standard orders or 14 days on average for STAT orders.

Once a specimen has started the testing process in our lab, the most accurate prediction of TAT will be displayed in the myPrevent portal as an Estimated Report Date (ERD) range. We calculate the ERD for each specimen as testing progresses; therefore the ERD range may differ from our published average TAT. View more about turnaround times here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.

EMAIL CONTACTS

Genetic Counselors

Geneticist

Clinical Features and Genetics

Clinical Features

Fetal akinesia deformation sequence (FADS, known also as Pena-Shokeir syndrome, type I) is characterized by prenatal onset growth deficiency, multiple joint contractures, facial anomalies, hypoplastic dermal ridges, and pulmonary hypoplasia. Patients are often stillborn and most live-born patients succumb to the effects of pulmonary hypoplasia in the first month of life. Limbs are also affected by camptodactyly, rocker bottom feet and clubfoot. Affected pregnancies may be complicated by polyhydramnios and some patients are born prematurely. Lethal congenital contracture syndrome 1 (LCCS1) and lethal arthrogryposis with anterior horn cell disease (LAAHD) are GLE1-associated disorders that closely resemble FADS. Findings that differentiate GLE1 disorders from FADS are fetal hydrops and generalized thinning of tubular bones. Fetal death often occurs before 32 weeks gestation, and diminished numbers of anterior motor neurons have been reported (Vuopala et al. 1995). Lethal multiple pterygium syndrome (LMPS) is characterized by prenatal growth deficiency, contractures, pterygia, and dysmorphic facies. Contractures and pterygia are universal findings. Patients are stillborn or do not survive beyond the newborn period. Pulmonary hypoplasia is likely the primary cause of mortality. LMPS pregnancies are complicated by hydrops. A markedly severe form of nemaline myopathy (NEM-8), caused by mutations of the KLHL40 gene, presents with fetal akinesia or hypokinesia and deformations, including contractures and fractures, at birth (Ravenscroft et al. 2013). Compton-North congenital myopathy is a severe, congenital myopathy with fetal akinesia and distinct secondary losses of beta-2-syntrophin and alpha-dystrobrevin observed in muscle biopsy. Clinical findings include reduced fetal movement, polyhydramnios, premature birth, severe hypotonia, absent deep tendon reflexes, and skeletal, bulbar, and respiratory weakness (Compton et al. 2008; Jones et al. 2003).

Genetics

Each of these disorders is inherited in an autosomal recessive manner. Abnormalities in genes encoding proteins involved with neuromuscular transmission (CHRNA1, CHRND, CHRNG, DOK7, RAPSN, MUSK) underlie some cases of FADS and LMPS. Other causes include primary neurogenic (Hageman et.al. 1987), prenatal exposure (Lavi et.al. 1991), and circulating maternal antibodies to the acetylcholine receptor (Brueton et al. 2000). LCCS1 and LAAHD result from defective export of polyadenylated mRNA secondary to GLE1 mutations. KLHL40 encodes a Kelch repeat containing protein that is expressed in striated muscle predominately during fetal development (Ravenscroft et al. 2013). CNTN1 encodes contactin-1, a neural immunoglobulin family adhesion protein that is expressed at the neuromuscular junction as well as in the central and peripheral nervous system. Mutations in CHRNE and COLQ are leading causes of congenital myasthenic syndrome and can lead to severe clinical condition which may mimic FADS (Byring et al. 2002). See individual gene test descriptions for additional information on molecular biology of gene products.

Clinical Sensitivity - Sequencing with CNV PGxome

Because of extensive genetic heterogeneity for these disorders and because an undetermined number of cases are non genetic, sensitivity cannot be accurately predicted. Analytical sensitivity should be high because nearly all mutations reported are detectable by sequencing (Human Gene Mutation Database).

Clinical sensitivity for del/dup testing is expected to be low as few gross duplications or deletions have been reported (Human Gene Mutation Database).

Testing Strategy

This test is performed using Next-Gen sequencing with additional Sanger sequencing as necessary.

This panel typically provides 100% coverage of all coding exons of the genes plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define coverage as ≥20X NGS reads or Sanger sequencing.

Since this test is performed using exome capture probes, a reflex to any of our exome based tests is available (PGxome, PGxome Custom Panels).

Indications for Test

Individuals with presentations consistent with fetal akinesia deformation sequence or lethal multiple pterygium syndrome.

Genes

Official Gene Symbol OMIM ID
CHRNA1 100690
CHRND 100720
CHRNE 100725
CHRNG 100730
CNTN1 600016
COLQ 603033
DOK7 610285
GLE1 603371
KLHL40 615340
MUSK 601296
RAPSN 601592
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Related Test

Name
PGxome®

Citations

  • Brueton LA, Huson SM, Cox PM, Shirley I, Thompson EM, Barnes PR, Price J, Newsom-Davis J, Vincent A. 2000. Asymptomatic maternal myasthenia as a cause of the Pena-Shokeir phenotype. Am J Med Genet 92: 1-6. PubMed ID: 10797415
  • Byring RF, Pihko H, Tsujino A, Shen XM, Gustafsson B, Hackman P, Ohno K, Engel AG, Udd B. 2002. Congenital myasthenic syndrome associated with episodic apnea and sudden infant death. Neuromuscul Disord 12: 548-553. PubMed ID: 12117478
  • Compton AG, Albrecht DE, Seto JT, Cooper ST, Ilkovski B, Jones KJ, Challis D, Mowat D, Ranscht B, Bahlo M, Froehner SC, North KN. 2008. Mutations in Contactin-1, a Neural Adhesion and Neuromuscular Junction Protein, Cause a Familial Form of Lethal Congenital Myopathy. The American Journal of Human Genetics 83: 714–724. PubMed ID: 19026398
  • Hageman G, Willemse J, van Ketel BA, Barth PG, Lindhout D. 1987. The heterogeneity of the Pena-Shokeir syndrome. Neuropediatrics 18: 45-50. PubMed ID: 3561707
  • Human Gene Mutation Database (Bio-base).
  • Jones K., Compton A., Yang N, Mills M., Peters M., Mowat D, Kunkel L., Froehner S., North K. 2003. Deficiency of the syntrophins and α-dystrobrevin in patients with inherited myopathy. Neuromuscular Disorders 13: 456–467. PubMed ID: 12899872
  • Lavi E, Montone KT, Rorke LB, Kliman HJ. 1991. Fetal akinesia deformation sequence (Pena-Shokeir phenotype) associated with acquired intrauterine brain damage. Neurology 41: 1467-1468. PubMed ID: 1891100
  • Ravenscroft G, Miyatake S, Lehtokari V-L, Todd EJ, Vornanen P, Yau KS, Hayashi YK, Miyake N, Tsurusaki Y, Doi H, Saitsu H, Osaka H, Yamashita S, Ohya T, Sakamoto Y, Koshimizu E, Imamura S, Yamashita M, Ogata K, Shiina M, Bryson-Richardson RJ, Vaz R, Ceyhan O, Brownstein CA, Swanson LC, Monnot S, Romero NB, Amthor H, Kresoje N, Sivadorai P, Kiraly-Borri C, Haliloglu G, Talim B, Orhan D, Kale G, Charles AK, Fabian VA, Davis MR, Lammens M, Sewry CA, Manzur A, Muntoni F, Clarke NF, North KN, Bertini E, Nevo Y, Willichowski E, Silberg IE, Topaloglu H, Beggs AH, Allcock RJ, Nishino I, Wallgren-Pettersson C, Matsumoto N, Laing NG. 2013. Mutations in KLHL40 Are a Frequent Cause of Severe Autosomal-Recessive Nemaline Myopathy. The American Journal of Human Genetics 93: 6-18. PubMed ID: 23746549
  • Vuopala K, Mäkelä-Bengs P, Suomalainen A, Herva R, Leisti J, Peltonen L. 1995. Lethal congenital contracture syndrome (LCCS), a fetal anterior horn cell disease, is not linked to the SMA 5q locus. J Med Genet. 32:36-38. PubMed ID: 7897624

Ordering/Specimens

Ordering Options

We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.

myPrevent - Online Ordering

  • The test can be added to your online orders in the Summary and Pricing section.
  • Once the test has been added log in to myPrevent to fill out an online requisition form.

Requisition Form

  • A completed requisition form must accompany all specimens.
  • Billing information along with specimen and shipping instructions are within the requisition form.
  • All testing must be ordered by a qualified healthcare provider.

For Requisition Forms, visit our Forms page


Specimen Types

Specimen Requirements and Shipping Details

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ORDER OPTIONS

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2) Select Additional Test Options

STAT and Prenatal Test Options are not available with Patient Plus.

No Additional Test Options are available for this test.

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