Fragile X syndrome (FXS, OMIM#300624) is the most common inherited cause of X-linked intellectual disability and behavior difficulties. In 99% of cases, it is caused by the pathological expansion (>200 repeats, full mutation -FM) of the CGG trinucleotide located at the 5′ UTR of the FMR1 (Fragile X Messenger Ribonucleoprotein 1) gene, leading to the lack of production of the FMRP. Clinical manifestations are well known in boys but are sometimes overlooked in girls, who may remain underdiagnosed. Premutation (PM) populations (55–200 repeats) may present other medical issues, such as FXPOI or FXTAS. Mosaic conditions, such as a combination of PM and FM lines in the same patient, may lead to milder phenotypes. With the improvement of genetic testing, information regarding the exact number of CGG triplet repeats and methylation status could help explain milder phenotypes in patients who may produce some FMRP. Chromosome X preferential inactivation (XCI) in FXS women can also play a role in clinical severity. We present four non-related families who were followed up in our FXS clinic. Some of their members showed FM on Southern blot, but had milder symptoms than expected. To rule out size mosaicism, a RT-PCR was performed, giving a different and more consistent molecular diagnosis. When mosaicism was not present, methylation status was performed, excluding full methylation. For females, XCI showed preferential inactivation in one case. Revisiting old molecular diagnoses should be considered in clinical practice, especially for patients with a milder phenotype than expected from their molecular reports. This personalized follow up may change their former diagnosis, prognosis, and expectations.

OBJECTIVES: To describe temporal trends and instantaneous relationships between middle cerebral artery (MCA) cerebral blood flow velocity, cerebral oxygen saturation (Csat), cerebral fractional tissue oxygen extraction (cFTOE), and systemic arteriovenous oxygen difference (AV o ₂ ) during the first 24 hours following congenital heart disease (CHD) surgery requiring cardiopulmonary bypass (CPB). DESIGN: Prospective observational study conducted from August 2021 to June 2022. SETTING: Single-center pediatric cardiac ICU in Canada. PATIENTS: Fifteen ventilated neonates and infants admitted to the PICU following CHD surgery requiring CPB. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Bilateral transcranial Doppler (TCD) assessments of the MCA were performed at seven predefined time points during the first 24 hours following CPB, with time 0 defined as the end of CPB. A total of 87 simultaneous measurements of systemic oxygen saturation, Csat, TCD-derived parameters, and AV o ₂ were analyzed. The nadir in MCA velocities occurred at a mean of 9.3 hours ( sd , 1.7 hr) post-CPB and coincided with the lowest Csat and the highest AV o ₂ difference and cFTOE. Lower MCA mean velocities were associated with higher AV o ₂ difference and increased cFTOE. CONCLUSIONS: In neonates and infants following CPB, MCA velocities reach its lowest point approximately 9 hours post-CPB, coinciding with the highest AV o ₂ difference and previously published nadir of cardiac output. These findings could suggest a period of relative cerebral hypoperfusion. Future studies should evaluate whether targeted interventions guided by multimodal cerebral monitoring can mitigate the risk of acute and long-term brain injury in this vulnerable population.