FOXG1

Angelman and Rett syndrome are neurodevelopmental disorders with significant phenotypic overlap. Classic Rett syndrome is a progressive disorder characterized by acquired microcephaly, loss of purposeful hand movements, and autistic behaviors, following a period of normal growth and development. Additional features include scoliosis, epilepsy, poor growth, and irregular breathing. There is broad clinical variability in the severity of Rett syndrome, including variants of Rett syndrome which may be associated with atypical features compared to the classic phenotype. Classic Rett syndrome primarily affects females.

 Angelman syndrome is characterized by functionally severe developmental delay or intellectual disability, movement or balance disorders of variable severity, behavioral uniqueness exemplified by apparent happy demeanor (frequent laughing/smiling) and easy excitability, and severe speech impairment. Other characteristics noted in over 80% of patients include microcephaly, seizures, and a specific, abnormal EEG pattern.  Patients may also exhibit wide mouths with unusual tongue/mouthing behaviors, hypopigmentation, and abnormal sleep-wake cycles.  Older patients may experience obesity.

This oligonucleotide microarray-based assay allows for the detection of exonic deletions or duplications of 105 genes currently tested in our laboratory. This is a custom designed array by Agilent technologies that contains ~140,000 probes present in a 4x180K format with probes more densely spaced in the exons of the genes being tested.  The array has been designed to detect copy number changes as small as 300-400 bp.  Single genes and custom panels of clinically related genes can be analyzed for deletions and duplications and results may be confirmed by qPCR, MLPA or alternative methodologies.

This assay will allow deletion/duplication analysis for disorders known to be caused by deletions or duplications within a single gene as well as for disorders for which the frequency of gene deletions/duplications is currently not well established. The array-CGH test is particularly indicated for disorders resulting from loss of function or haploinsufficiency. In addition, testing for exonic deletions/duplications is useful in autosomal recessive conditions in which only one mutation is identified by sequence analysis.  This assay will detect exonic deletions/duplications of the 105 genes on the array that may not be detected by whole genome array CGH.

Rett syndrome is a progressive neurodevelopmental disorder, primarily affecting females. Rett syndrome is characterized by acquired microcephaly, loss of purposeful hand movements, and autistic behaviors, following a period of normal growth and development. Additional features include scoliosis, epilepsy, poor growth, and irregular breathing. There is broad clinical variability in the severity of Rett syndrome, including other variants of Rett syndrome.

• MeCP2 mutations are present in 70-90% of females with classic Rett syndrome and approximately 20% of females with atypical Rett syndrome.  Partial deletions of MeCP2 are found in approximately 16% of girls with classic or atypical Rett syndrome.
• CDKL5 mutations have been demonstrated in a broad spectrum of phenotypes including atypical Rett syndrome with infantile spasms.
• Mutations of the MEF2C gene have been identified in patients with severe mental retardation, stereotypic movements, hypotonia, and epilepsy. Phenotypic overlap exists between patients with MEF2C mutations and atypical Rett syndrome.
• Abnormalities of the FOXG1 gene have been identified in patients with the congenital variant of Rett syndrome. Patients with the congenital variant of Rett syndrome have features similar to classic Rett syndrome, but hypotonia and severe developmental delay starts in the first months of life.  

We offer full gene sequencing for all coding exons and the intron/exon boundaries of MECP2, CDKL5, MEF2C, and FOXG1 as well as deletion/duplication analysis for all four genes by array-CGH. These tests are offered together as a panel or separately (see individual tests for pricing on separate tests).