Luis Fernández

Background/Objectives: Current guidelines recommend 24–48 h Holter for risk stratification and atrial fibrillation (AF) screening in hypertrophic cardiomyopathy (HCM). However, the limited duration of this approach may not provide optimal sensitivity. In addition, extended ECG monitoring has been demonstrated to be more effective in detecting arrhythmias in other clinical entities. We aimed to assess the utility of extended ECG monitoring for 30 days in a non-high-risk cohort of HCM patients. Methods: We conducted a prospective multicentre study with 113 non-high-risk HCM patients who underwent 30-day ECG monitoring with a dedicated device. We compared the detection of relevant arrhythmias (AF, atrial flutter, and non-sustained ventricular tachycardia) during 30-day monitoring with the findings observed during the first 24 h. Results: Extended ECG monitoring detected relevant arrhythmias in 63.7% of patients, compared with 12.4% during the first 24 h (p < 0.001). This difference was mainly driven by non-sustained ventricular tachycardia (NSVT) (61.1% vs. 8.9%, p < 0.001). Atrial fibrillation episodes were detected in 10.6% of patients after completing prolonged monitoring vs. 6.2% during the first 24 h (p = 0.066). Extended monitoring resulted in a reclassification of 21.2% of patients to a higher sudden cardiac death (SCD) risk category using the HCM-SCD calculator. Conclusions: Extended ECG monitoring significantly enhances the detection of arrhythmias in HCM. Using this technique, NSVT were detected in most patients of a non-high-risk HCM cohort. Further investigation is warranted to determine the role of extended monitoring in SCD risk stratification and AF screening.

We present a 28‐year‐old Spanish female with a de novo heterozygous variant in FMR1 (NM_002024.6:c.1061_1062delAA), p.(Lys354Thrfs*15) detected by whole‐exome sequencing and confirmed by Sanger sequencing from cDNA. She was born full‐term with neonatal jaundice requiring phototherapy. At age 11, she exhibited weight and head circumference > 97th percentile, global developmental delay, mild ID (IQ: 71), and hyperactivity. FMR1 CGG analysis was normal. NGS panel of over 200 OGS‐related genes found no pathogenic variants. By age 28, she presented with macrocephaly, coarse facial features, mild joint hypermobility, left talo‐valgus, a port‐wine stain, a café‐au‐lait spot, and a piezogenic papule. Herein, we describe a clinical and molecular report of the second FXS female patient due to a heterozygous point variant. This study was approved by the ethical committee of Hospital Universitario La Paz (CEIm PI‐446), and informed consent was obtained from the patient and her parents.

The 22q11.2 region is highly susceptible to genomic rearrangements leading to multiple genomic disorders, including 22q11.2 microdeletion syndrome (22q11.2 DS) (MIM# 188400), 22q11.2 microduplication syndrome (MIM# 608363), supernumerary der(22)t(11;22) syndrome (also known as Emanuel Syndrome; MIM# 609029), and Cat Eye Syndrome (MIM# 115470). In this study, we present data on causes of mortality, average age of death, and the existing associated risk factors in patients with 22q11.2 rearrangements. Our cohort included 223 patients (120 males and 103 females) with confirmed diagnoses of 22q11.2 rearrangements diagnosed through molecular techniques (FISH, MLPA, and CMA). Relatives from patients who have been molecularly confirmed with 22q11.2 rearrangements have also been added to the study, regardless of the presence or absence of symptoms. Of these 223 individuals, 21 (9.4%) died. Deceased patients’ rearrangements include 19 microdeletions, 1 microduplication, and 1 patient with a marker chromosome. The median age of death was 3 months and 18 days (ranging from 3 days to 34 years). There were 17 patients who died at pediatric age (80.95%), 3 died at adult age (14.28%), and for 1 of whom, the age of death is unknown (4.76%). Eighteen patients were White Mediterranean (European non-Finnish) (85.71%) whereas three were Amerindian (South American) (14.28%). Mortality from cardiac causes accounted for 71.42%. The second most frequent cause of death was sepsis in two patients (9.52%). One patient died from respiratory failure (4.76%) and one from renal failure (4.76%). Information regarding the cause of death was not available in two patients (9.52%). Most patients who died were diagnosed within the first week of life, the majority on the first day. This study adds additional information on mortality in one of the largest cohorts of patients with 22q11.2 rearrangements in more than 30 years of follow-up.

Schizophrenia (SCZ) is a severe and chronic neurodevelopmental disorder with onset occurring during adolescence or early adulthood; notwithstanding, the brain dysfunction occurs before the disease and is not clinically evident. Recently, memantine (MEM) had been postulated as an effective preventive treatment in rats. In this study, was performed the Early Maternal Deprivation (EMD) protocol in Sprague–Dawley rats, establishing four groups (control, EMD, EMD treated with MEM, and MEM treatment). Behavioral parameters such as active linking (AL) and T maze were evaluated as well as quantitative brain histological changes at 3, 7, and 10 weeks of age, to understand the longitudinal demeanor of the disease. Prefrontal evoked potentials (PFEPs) were recorded to study functional synaptic connectivity and neuronal synchronicity changes. The results showed that EMD induces a decrease of AL and poor performance of T maze, in addition to volumetric changes of cortical and subcortical brain structures and abnormalities in PFEPs. The majority of this changes were absent by neonatal MEM administration. Taking into account that all these abnormalities are associated to SCZ, we propose to MEM as a potential preventive treatment.

We and others have previously reported that familial cytogenetic studies in apparently de novo genomic imbalances may reveal complex or uncommon inheritance mechanisms. A familial, combined genomic and cytogenetic approach was systematically applied to the parents of all patients with unbalanced genome copy number changes. Discordant array-CGH and FISH results in the mother of a child with a prenatally detected 16p13.11 interstitial microduplication disclosed a balanced uncommon rearrangement in this chromosomal region. Further dosage and haplotype familial studies revealed that both the maternal grandfather and uncle had also the same 16p duplication as the proband. Genomic compensation observed in the mother probably occurred as a consequence of interchromosomal postzygotic nonallelic homologous recombination. We emphasize that such a dualistic strategy is essential for the full characterization of genomic rearrangements as well as for appropriate genetic counseling.