Here is Olivia’s story diagnosed with TFE3-related neurodevelopmental disorder.
Olivia’s features shown before and at birth
Olivia had ultrasonography before birth, and was suspected of having a Dandy-walker variant. In January 2017, fetal MRI was conducted, and cerebellar development was found normal. When checking up her body conditions after birth, no anomalies were found. The echoencephalography and brain MR results found suspicious mega cisterna magna (enlargement of the CSF space in the posterior cranial fossa) but found nothing else.
Physical examination results
Doctors conducted several tests to find her problems and causes.
Her karyotype test result was found normal. However, echocardiography found mildly dilated left atrium and left ventricle, which gradually has resolved. Abdominal sonography has found dysplastic right kidney.
Olivia’s first visit to the hospital
When Olivia was 8-month-old, she presented with delayed development skills such as poor head control and not rolling over.
Physical examination at the moment found the following features: Anteverted nares, broad flat nasal bridge, coarse facial features, widely spaced eyes, full cheeks, widely spaced eyes, facial hypertrichosis, thin lip. Streaky marble-like hyperpigmentation was also found from the neck, trunk, and inguinal areas.
Olivia went through some other examinations, and the test results found no unusual problems. Chromosome karyotyping results found normal with 46 chromosomes, with XX chromosome. Multiplex Ligation-dependent Probe Amplification (MLPA) found no microdeletion detected in 26 microdeletion syndrome regions. Metabolic workup results were also found normal.
Whole exome sequencing and reanalysis
In July 2018, Olivia took Whole Exome Sequencing (WES) with 3billion’s rare disease genetic testing. However, there was no relevant variant detected at that time. 3billion first started running its reanalysis system every 6 months. In June 2020, 3billion started running the reanalysis every day. Until now, 3billion’s daily reanalysis system reflects new gene-disease evidence every day, continuously analyzing the undiagnosed patients’ genome data until they get diagnosed.
Olivia, finally diagnosed with regular reanalysis
Olivia was diagnosed with 3billion’s daily reanalysis system after 8 months the system launched.
In February 2021, she got diagnosed with De novo rare disease, with new evidence related to Olivia’s symptoms and genetic variant information. She had the matching variant and symptoms with the ones mentioned in the paper, ‘De novo mutations in the X-linked TFE3 gene cause intellectual disability with pigmentary mosaicism and storage disorder-like features’, and her parental testing confirmed the variant.
TFE3-related neurodevelopmental disorder (No registered name yet) Gene: TFE3
Genomic position: X-48895943-T-C
HGVS nomenclature: NM_006521.4 c.599A>G p.Thr187Ala
Rule: PS1, PM2, PP3
Related article: ‘De novo mutations in the X-linked TFE3 gene cause intellectual disability with pigmentary mosaicism and storage disorder-like features’