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Congenital Variant Rett syndrome or FOXG1 syndrome via the FOXG1 Gene

Summary and Pricing

Test Method

Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture Probes
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
8637 FOXG1 81404 81404,81479 $640 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
8637FOXG181404 81404(x1), 81479(x1) $640 Order Options and Pricing

Pricing Comments

This test is also offered via our exome backbone with CNV detection (click here). The exome-based test may be higher priced, but permits reflex to the entire exome or to any other set of clinically relevant genes.

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

Turnaround Time

18 days on average for standard orders or 13 days on average for STAT orders.

Please note: Once the testing process begins, an Estimated Report Date (ERD) range will be displayed in the portal. This is the most accurate prediction of when your report will be complete and may differ from the average TAT published on our website. About 85% of our tests will be reported within or before the ERD range. We will notify you of significant delays or holds which will impact the ERD. Learn 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

  • Li Fan, MD, PhD, FCCMG, FACMG

Clinical Features and Genetics

Clinical Features

Congenital variant Rett syndrome (congenital RTT) is a neurodevelopmental disorder characterized by severe intellectual disability. Congenital RTT patients present with hypotonia and psychomotor delay during infancy. Unlike classic RTT, most congenital RTT patients do not undergo a clear period of developmental regression. Other common features of congenital RTT include: severe intellectual disability, epilepsy, acquired microcephaly, stereotyped hand motions, poor eye contact, limited or absent language skills, sleep disturbances and gastro-oesophageal reflux (Kortum et al. 2011). Many congenital RTT patients exhibit severe motor impairment and are unable to walk (De Filippis et al. 2012). Brain MRI of congenital RTT patients reveals a simplified gyral pattern, reduced white matter volume and corpus callosum hypoplasia.

Genetics

Congenital RTT is caused by heterozygous mutations in the FOXG1 gene. Reported cases of RTT are sporadic and result from de novo FOXG1 mutations. Pathogenic missense, nonsense and frameshift mutations as well as large deletions and duplications encompassing FOXG1 have been reported (Bertossi et al. 2013, Kortum et al. 2011). FOXG1 encodes a forkhead family transcription factor that acts as a transcriptional repressor. The FoxG1 protein is expressed in the brain and predominantly localizes to the nucleus where it associates with chromatin in a dynamic manner (De Filippis et al. 2012). FoxG1 regulates development of the embryonic telencephalon which eventually gives rise to the adult cortex, hippocampus, olfactory bulbs and basal ganglia (Martynoga et al. 2005). FoxG1 also promotes the survival of post-mitotic neurons in vitro, suggesting a continuing role for FoxG1 in the adult brain (Dastidar et al. 2011). In support of FoxG1 promoting neuronal survival, an adult patient with a FOXG1 missense mutation was reported who displayed symptoms of late-onset parkinsonism, a condition usually resulting from neuronal cell loss (Méneret et al. 2012).

Clinical Sensitivity - Sequencing with CNV PG-Select

Pathogenic variants in FOXG1 were identified in ~3% (4 of 125) patients diagnosed with intellectual disability, microcephaly or callosal abnormalities (Kortum et al. 2011). In another study, FOXG1 mutations were found in 8% (2 of 25) of patients with a RTT diagnosis, but who lacked causative MECP2 mutations (Van der Aa et al. 2010).

Testing Strategy

This test provides full coverage of all coding exons of the FOXG1 gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.

Indications for Test

Candidates for FOXG1 testing include male patients with an RTT diagnosis and female patients with RTT-like symptoms, but for which no causative MECP2 variant was found (Van der Aa et al. 2010). FOXG1 testing is particularly recommended in RTT-like cases in which no clear period of regression is seen (Kortum et al. 2011).

Gene

Official Gene Symbol OMIM ID
FOXG1 164874
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Rett Syndrome, Congenital Variant AD 613454

Citations

  • Bertossi C, Cassina M, Palma L De, Vecchi M, Rossato S, Toldo I, Donà M, Murgia A, Boniver C, Sartori S. 2013. 14q12 duplication including FOXG1: Is there a common age-dependent epileptic phenotype? Brain and Development. PubMed ID: 23838309
  • Dastidar SG, Landrieu PMZ, D’Mello SR. 2011. FoxG1 Promotes the Survival of Postmitotic Neurons. Journal of Neuroscience 31: 402–413. PubMed ID: 21228151
  • De Filippis R, Pancrazi L, Bjørgo K, Rosseto A, Kleefstra T, Grillo E, Panighini A, Cardarelli F, Meloni I, Ariani F, Mencarelli M, Hayek J, et al. 2012. Expanding the phenotype associated with FOXG1 mutations and in vivo FoxG1 chromatin-binding dynamics. Clinical Genetics 82: 395–403. PubMed ID: 22091895
  • Kortum F, Das S, Flindt M, Morris-Rosendahl DJ, Stefanova I, Goldstein A, Horn D, Klopocki E, Kluger G, Martin P, Rauch A, Roumer A, et al. 2011. The core FOXG1 syndrome phenotype consists of postnatal microcephaly, severe mental retardation, absent language, dyskinesia, and corpus callosum hypogenesis. Journal of Medical Genetics 48: 396–406. PubMed ID: 21441262
  • Martynoga B, Morrison H, Price DJ, Mason JO. 2005. Foxg1 is required for specification of ventral telencephalon and region-specific regulation of dorsal telencephalic precursor proliferation and apoptosis. Developmental Biology 283: 113–127. PubMed ID: 21418559
  • Méneret A, Mignot C, An I, Habert M-O, Jacquette A, Vidailhet M, Bienvenu T, Roze E. 2012. Generalized dystonia, athetosis, and parkinsonism associated with FOXG1 mutation. Mov. Disord. 27: 160–161. PubMed ID: 21953941
  • Van der Aa N, Bergh M Van den, Ponomarenko N, Verstraete L, Ceulemans B, Storm K. 2010. Analysis of FOXG1 Is Highly Recommended in Male and Female Patients with Rett Syndrome. Molecular Syndromology 1: 290–293. PubMed ID: 22190898

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.
  • PGnome sequencing panels can be ordered via the myPrevent portal only at this time.

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

View Ordering Instructions

1) Select Test Method (Backbone)


1) Select Test Type


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.

Note: acceptable specimen types are whole blood and DNA from whole blood only.
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