Test Code: 9170

Congenital Variant Rett Syndrome: FOXG1 Gene Deletion/Duplication
Test Code: 9170
Turnaround time: 3 weeks

CONDITION DESCRIPTION

Mutations and deletions of the FOXG1 gene (14q13) cause a developmental disorder known as a Congenital Variant of Rett syndrome. Common features include severe postnatal microcephaly, severe intellectual disability with absent language, apraxia, hypogenesis of the corpus callosum, jerky movements and generalized seizures. These individuals have normal body measurements at birth but then have slow growth after leading to low weight and low normal stature. Sleep was reported to be disrupted starting in infancy and stereotypical hand movements were observed. Unlike Rett syndrome, individuals with a FOXG1 mutation do NOT have any periods of normal development.

Duplications of the FOXG1 gene have been associated with developmental epilepsy, intellectual disability, and severe speech impairment.

For patients with suspected Congenital Variant of Rett syndrome, sequence analysis is recommended as the first step in mutation identification. For patients in whom mutations are not identified by full gene sequencing, deletion/duplication analysis is appropriate.

References:
• Kortum et al. (2011). J Med Genet, 48:396-406.
• OMIM #613454: Congenital Variant Rett syndrome
• OMIM #164874: FOXG1 gene

GENES

FOXG1

INDICATIONS

This test is indicated for:

  • Confirmation of a clinical diagnosis of Congenital Variant Rett syndrome in an individual in whom sequence analysis was negative.
  • Carrier testing in adults with a family history of Congenital Variant Rett syndrome in whom sequence analysis was negative.

METHODOLOGY

DNA isolated from peripheral blood is hybridized to a CGH array to detect deletions and duplications. The targeted CGH array has overlapping probes which cover the entire genomic region.

Please note that a “backbone” of probes across the entire genome are included on the array for analytical and quality control purposes. Rarely, off- target copy number variants causative of disease may be identified that may or may not be related to the patient’s phenotype. Only known pathogenic off-target copy number variants will be reported. Off-target copy number variants of unknown clinical significance will not be reported.

Detection is limited to duplications and deletions. The CGH array will not detect point or intronic mutations. Results of molecular analysis must be interpreted in the context of the patient’s clinical and/or biochemical phenotype.

SPECIMEN REQUIREMENTS

Submit only 1 of the following specimen types

* Preferred specimen type: Whole Blood

Type: Whole Blood

Specimen Requirements:

In EDTA (purple top) or ACD (yellow top) tube: Infants (2 years): 3-5 ml
Older Children & Adults: 5-10 ml
Specimen Collection and Shipping: Refrigerate until time of shipment. Ship sample within 5 days of collection at room temperature with overnight delivery.

Type: Saliva

Specimen Requirements:
OrageneTM Saliva Collection kit (available through CEN4GEN) used according to manufacturer instructions.
Specimen Collection and Shipping: Store sample at room temperature. Ship sample within 5 days of collection at room temperature with overnight delivery.

SPECIAL INSTRUCTIONS

Sequence analysis is required before deletion/duplication analysis by targeted CGH array. If sequencing is performed by another third party provider, please submit a copy of the sequencing report with the test requisition.

RELATED TESTS

  • Sequence analysis of the FOXG1 gene is available and is required before deletion/duplication analysis.
  • Custom diagnostic mutation analysis (test code: 6875) is available to family members if mutations are identified by targeted mutation testing or sequencing analysis.