Fetal Concerns Panel

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy GenesCPT Code Copy CPT Codes
4777 BRAF 81406,81479 Add to Order
CBL 81479,81479
CHRNA1 81479,81479
CHRND 81479,81479
CHRNG 81479,81479
CTSA 81479,81479
DHCR7 81405,81479
DOK7 81479,81479
GALNS 81479,81479
GBA 81479,81479
GLB1 81479,81479
GLE1 81479,81479
GNPTAB 81479,81479
GUSB 81479,81479
HRAS 81404,81479
IDUA 81406,81479
KAT6B 81479,81479
KCNH2 81406,81479
KCNQ1 81406,81479
KLHL40 81479,81479
KRAS 81405,81479
LIPA 81479,81479
MAP2K1 81406,81479
MAP2K2 81406,81479
MUSK 81479,81479
NRAS 81479,81479
PEX1 81479,81479
PEX10 81479,81479
PEX12 81479,81479
PEX26 81479,81479
PEX6 81479,81479
PTPN11 81406,81479
RAF1 81406,81479
RAPSN 81479,81479
RIT1 81479,81479
SCN5A 81407,81479
SHOC2 81405,81479
SLC17A5 81479,81479
SOS1 81406,81479
SUMF1 81479,81479
Full Panel Price* $890
Test Code Test Copy Genes Total Price CPT Codes Copy CPT Codes
4777 Genes x (40) $890 81404, 81405(x3), 81406(x9), 81407, 81479(x66) Add to Order

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.

Targeted Testing

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

Turnaround Time

18 days on average

EMAIL CONTACTS

Genetic Counselors

Geneticist

Clinical Features and Genetics

Clinical Features

Miscarriage, the spontaneous loss of pregnancy before the fetus has reached viability, occurs in 15% of clinically recognized pregnancies, but is estimated to be 4 to 5 times more frequent when preclinical losses are considered. Approximately 1 in 4 women will experience a miscarriage in her lifetime (van den Berg et al. 2012; Hardy and Hardy 2015). Risk factors associated with miscarriage include increased maternal age, previous miscarriage, infertility or assisted reproduction, low body mass index, increased alcohol consumption, stress, and increased paternal age (Maconochie et al. 2007). In at least 50% of miscarriages, a chromosomal imbalance can be detected (van den Berg et al. 2012; Sahoo et al. 2016).

Stillbirth is defined as fetal death at or after 20 weeks of gestation and occurs in approximately 1 in 160 pregnancies in the United States. Stillbirth is the most common adverse outcome of pregnancy with approximately 2.64 million stillbirths occurring worldwide in 2009 (Wou et al. 2014). In 2013, there were more stillbirths than neonatal deaths in the United States (MacDorman and Gregory 2015). Stillbirths are more common in non-Hispanic black women, teenagers, women 35 years or over, pregnancies with male fetuses, and in pregnancies with multiple fetuses. Other maternal risk factors include obesity, smoking, hypertension, diabetes, and prior stillbirth or miscarriage (MacDorman and Gregory 2015). The main known causes of stillbirth are obstetric conditions, placental factors (including abruptio placentae), infection, and fetal malformations, including intrauterine growth restriction (IUGR). However, in more than 25% of instances, the reason for the stillbirth is unknown (The Stillbirth Collaborative Research Writing Group 2011; Wou et al. 2014). It has been estimated that 25% of stillbirths can be attributed to genetic etiologies (Wapner 2010). Moreover, a recent study of nearly 3,000 stillbirths conducted by the Wisconsin Stillbirth Service Program (WiSSP), found that at least one minor anomaly is present in the majority of stillbirths and that the presence of minor anomalies is correlated with the presence of at least one major anomaly (McPherson and Cold 2016). In addition, another study from the WiSSP suggested that genetic causes may be more common with recurrent stillbirths (McPherson 2016).

Neonatal death is defined as the death of an infant within the first 28 days of life. It is estimated that there are approximately 4 million neonatal deaths annually worldwide and that these deaths account for 40% of deaths of children under 5 years of age (Jehan et al. 2009). There were nearly 16,000 neonatal deaths in the United States in 2013 (MacDorman and Gregory 2015). Risk factors for neonatal death are similar to those for stillbirth (Mathews and MacDorman 2010; MacDorman and Gregory 2015). The leading causes of neonatal death are congenital anomalies including chromosome abnormalities (Mathews and MacDorman 2010).

Genetics

There are two major categories of genetic etiology for miscarriage, stillbirth, and neonatal death: chromosome abnormalities including triploidy, common aneuploidies (chromosomes 13, 18, 21, and X), and other chromosomal imbalances (Wapner 2010), and single gene disorders, including, but not limited to, fetal akinesia syndrome, metabolic disorders, glycogen storage disorders, Noonan syndrome, and sudden cardiac death disorders (Wapner 2010; McPherson and Cold 2016; Sahoo et al. 2016). To date, chromosome abnormalities have been reported to be the most common, affecting at least 50% of miscarriages and 6% to 17% of stillbirths (Wapner 2010; Reddy et al. 2012; van den Berg et al. 2012; Sahoo et al. 2016). Chromosomal microarray (CMA) testing has been suggested as a first line test in both miscarriages and stillbirths because it does not require growing cells, as karyotyping does, and it will also detect submicroscopic imbalances (Reddy et al. 2012; ACOG 2013; Sahoo et al. 2016). No comprehensive studies have been conducted to determine the incidence of single gene disorders among miscarriages, stillbirths, or neonatal deaths without chromosome abnormalities.

This test involves sequencing of 40 genes encompassing several classes of genetic disorders that would be expected to increase the risk of miscarriage, stillbirth, or neonatal death. These disorders include fetal akinesia/lethal multiple pterygium syndrome, Smith-Lemli-Opitz syndrome (SLOS), Noonan syndrome, peroxisomal disorders, glycogen storage disorders, and long QT syndrome. Detailed test descriptions for these disorders can be found on our website under each disorder.

Testing Strategy

This panel typically provides ≥98% 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.

All genetic tests have limitations. In particular, this sequencing test does not detect large deletions or complex rearrangement between the functional GBA gene and its pseudogene.

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

Clinical Sensitivity - Sequencing with CNV

No comprehensive studies have been conducted to determine the contribution of each of the disorders included in the NextGen sequencing panel to miscarriage, stillbirth, and neonatal death, although stillbirths and neonatal deaths have been reported with each disorder (Crotti et al. 2013; Hopper et al. 2015; Klouwer et al. 2015; Hellmund et al. 2016; Gezdirici et al. 2016). Consequently, overall clinical sensitivity cannot be estimated at this time.

Chromosomal Microarray (CMA) identified clinically significant chromosomal imbalances in 3975/7396 (53.7%) of miscarriage specimens, with 94% of these considered causative. Moreover, CMA was successful in 7396/8118 (91.1%) of specimens, compared to a failure rate of 20% to 40% by karyotyping (Sahoo et al. 2016).

In a different study, CMA identified pathogenic variants in 44/532 (8.3%) of stillbirth samples compared to 31/532 (5.8%; P=0.007) cytogenetic abnormalities detected by karyotyping. When structural abnormalities were noted on postmortem examination, CMA identified pathogenic variants in 20/67 (29.9%) compared to 13/67 (19.4%; P=0.008) cytogenetic abnormalities detected by karyotyping. Moreover, CMA had a significantly lower failure rate (67/532, 12.6%) compared to karyotyping (157/532, 29.5%; P<0.001) (Reddy et al. 2012). No comprehensive studies of chromosomal abnormality rates in neonatal deaths were identified. However, the rate of chromosomal abnormalities among neonatal deaths would be expected to be similar to that in stillbirths.

CNV detection by NGS sequencing is expected to have a similar sensitivity to CMA for detecting clinically significant copy number variants.

Indications for Test

Candidates for this test include any unexplained miscarriage, stillbirth or neonatal death.

Diseases

Name Inheritance OMIM ID
Cardiofaciocutaneous syndrome 3 AD 615279
Cardiofaciocutaneous syndrome 4 AD 615280
Costello Syndrome AD 218040
Escobar Syndrome AR 265000
Fetal Akinesia Deformation Sequence AR 208150
Galactosialidosis AR 256540
Gaucher Disease, Perinatal Lethal AR 608013
Genitopatellar Syndrome AD 606170
I Cell Disease AR 252500
Infantile Gm1 Gangliosidosis AR 230500
Lethal Arthrogryposis With Anterior Horn Cell Disease AR 611890
Lethal Congenital Contracture Syndrome 1 AR 253310
Lethal Multiple Pterygium Syndrome AR 253290
Long QT Syndrome 1 AD 192500
Long QT Syndrome 2 AD 613688
Long QT Syndrome 3 AD 603830
Lysosomal Acid Lipase Deficiency AR 278000
Morquio Syndrome A AR 253000
Mucopolysaccharidosis Type VII AR 253220
Mucopolysaccharidosis, MPS-I-S AR 607016
Multiple Sulfatase Deficiency AR 272200
Nemaline Myopathy 8 AR 615348
Noonan Syndrome 1 AD 163950
Noonan Syndrome 3 AD 609942
Noonan Syndrome 4 AD 610733
Noonan Syndrome 5 AD 611553
Noonan Syndrome 6 AD 613224
Noonan Syndrome 7 AD 613706
Noonan Syndrome 8 AD 615355
Noonan Syndrome-Like Disorder With Or Without Juvenile Myelomonocytic Leukemia AD 613563
Noonan-Like Syndrome With Loose Anagen Hair AD 607721
Peroxisome biogenesis disorder 1A (Zellweger) AR 214100
Peroxisome biogenesis disorder 3A (Zellweger) AR 614859
Peroxisome biogenesis disorder 4A (Zellweger) AR 614862
Peroxisome biogenesis disorder 6A (Zellweger) AR 614870
Peroxisome biogenesis disorder 7A (Zellweger) AR 614872
Sialic Acid Storage Disease, Severe Infantile Type AR 269920
Smith-Lemli-Opitz Syndrome AR 270400

Related Test

Name
PGxome®

Citations

  • American College of Obstetricians and Gynecologists. 2013. ACOG committee opinion. Washington, DC: American College of Obstetricians and Gynecologists.
  • Crotti L. et al. 2013. JAMA. 309: 1473-82. PubMed ID: 23571586
  • Gezdirici A. et al. 2016. The Journal of Maternal-fetal & Neonatal Medicine Jun 8:1-4. [Epub ahead of print] PubMed ID: 27193571
  • Hardy K., Hardy, P.J. 2015. Translational Pediatrics. 4: 189-200. PubMed ID: 26835373
  • Hellmund A. et al. 2016. Archives of Gynecology and Obstetrics. 294(4): 697-707. PubMed ID: 26825730
  • Hopper R.K. et al. 2015. American Journal of Medical Genetics. Part A. 167A: 882-5. PubMed ID: 25706034
  • Jehan I. et al. 2009. Bulletin of the World Health Organization. 87: 130-8. PubMed ID: 19274365
  • Klouwer F.C. et al. 2015. Orphanet Journal of Rare Diseases. 10:151. PubMed ID: 26627182
  • MacDorman M.F., Gregory E.C.W. 2015. National Vital Statistics Reports. 64(8). PubMed ID: 26222771
  • Maconochie N. et al. 2007. Bjog. 114: 170-86. PubMed ID: 17305901
  • Mathews, TJ, MacDorman, MF. 2010. National Vital Statistics Reports. 58(17).
  • McPherson E. 2016. American Journal of Medical Genetics. Part A. 170A: 1174-80. PubMed ID: 26945668
  • McPherson E., Cold C. 2016. American Journal of Medical Genetics. Part A. 170A: 52-9. PubMed ID: 26373818
  • Reddy U.M. et al. 2012. The New England Journal of Medicine. 367: 2185-93. PubMed ID: 23215556
  • Sahoo T. et al. 2016. Genetics in Medicine. 0: N/A. PubMed ID: 27337029
  • The Stillbirth Collaborative Research Network Writing Group, 2011. JAMA. 306: 2459-68. PubMed ID: 22166605
  • van den Berg M.M. et al. 2012. Biochimica Et Biophysica Acta. 1822: 1951-9. PubMed ID: 22796359
  • Wapner R.J. 2010. Clinical Obstetrics and Gynecology. 53: 628-34. PubMed ID: 20661047
  • Wou K. et al. 2014. BMJ Open. 4: e004635. PubMed ID: 24902725

Ordering/Specimens

Ordering Options

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.

Specimen Types

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