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BACKGROUND: A prospective randomized controlled trial of exclusive human milk nutrition (EHM) in infants with single-ventricle physiology (SVP) was previously published. This study evaluates growth and health outcomes at 3-6 months. METHODS: Demographics, anthropometrics, and clinical outcomes were collected prospectively. Anthropometric z-scores were calculated using WHO standards. RESULTS: One hundred seven infants were randomized to EHM or control diet, with 23 infants meeting predefined exclusion criteria, 8 infants withdrawn/died, leaving 76 infants at discharge. At 3-6 months, 74 infants completed follow-up. Infants with hypoplastic left heart syndrome (HLHS) were similar (control 73%, EHM 86.5%; p = 0.24). Growth, z-scores, and hospitalization did not differ between groups up to 6 months. Median growth velocity was 25 (IQR: 20.24-30.99) and 22 (IQR: 18.76-23.94) g/day from birth to 3-6 months. Overall, 50-60% of infants achieved 100% PO intake by 3-6 months of age. CONCLUSIONS: Neonates with SVP receiving an EHM diet from birth to 30 days post-surgery had similar growth at 3-6 months of age compared to the control diet. Infants with SVP benefit from a protocolized nutritional approach, as evidenced by normal growth velocities in infancy. Centers may consider delaying gastrostomy tube placement until after the Glenn operation. TRIAL REGISTRATION: This trial is registered with ClinicalTrials.gov ( www. CLINICALTRIALS: gov , Trial ID: NCT02860702). IRB APPROVAL: This trial was approved by the Institutional Review Board of the University of Texas Health Sciences Center at San Antonio (ID: HSC20150779H). IMPACT: This multicenter RCT demonstrates the long-term benefits of exclusive human milk nutrition in infants with SVP, with improved growth and reduced necrotizing enterocolitis. A multidisciplinary approach and a well-thought-out nutritional algorithm can optimize growth in infants with complex congenital heart disease, similar to healthy term infants up to 6 months of age. The majority of infants with SVP requiring an operation within the first month of life are able to achieve 100% of their intake via PO by 6 months of age; therefore, delaying gastrostomy tube placement until after the Glenn operation may be considered.

RASopathies comprise a group of congenital malformation syndromes with predominant neuro-cardio-facial-cutaneous involvement resulting from pathogenic variants in RAS/mitogen-activated protein kinase (MAPK) signaling pathway genes. In this study 33 patients are presented with their clinical and molecular findings as an RASopathy cohort including a family with an AMMECR1-related disorder. The diagnostic distribution of the cohort included Noonan syndrome (n = 18), neurofibromatosis type 1 (n = 8), and single cases of cardiofaciocutaneous syndrome, Costello syndrome, neurofibromatosis-Noonan syndrome, NF1 microdeletion syndrome, Noonan syndrome-like disorder with loose anagen hair, Noonan syndrome with multiple lentigines and AMMECR1-related midface hypoplasia, hearing impairment, elliptocytosis, and nephrocalcinosis (MIM# 300990). The most prevalent clinical manifestations were dermatological findings (90.9%), skeletal features (84.4%), cardiovascular involvement (75.8%), and typical craniofacial dysmorphism suggestive of RASopathy (72.7%). Variants were most frequently identified in PTPN11 and NF1, followed by single cases involving the BRAF, HRAS, LZTR1, RAF1, RIT1, SHOC2, and SOS1. Notably, one patient harbored a variant in AMMECR1, which is not involved in the RAS/MAPK pathway. Overall, this study delineates the clinical and molecular landscape of a cohort from Türkiye and underscores that the AMMECR1-related phenotype represents a distinct entity that closely mimics Noonan syndrome.

We present a unique case of spontaneous chordal rupture in a young infant with Down syndrome and unrepaired transitional atrioventricular septal defect. This resulted in abrupt onset of severe left atrioventricular valve regurgitation, cardiogenic shock, and multiorgan dysfunction. Our case highlights the need for a high index of suspicion for a ruptured chord in a young infant presenting with acute onset of pulmonary edema.

Down syndrome, caused by trisomy 21, increases the risk of diverse co-occurring conditions. With more than 34,000 related publications indexed in PubMed as of early 2026, keeping pace with this expanding literature is challenging. While general-purpose large language models are widely used for information retrieval, they often rely on broad training data rather than specific evidence. Retrieval-augmented generation (RAG) improves rigor and reliability of responses by linking model outputs to source texts. In research, source texts are peer-reviewed articles. Standard implementations treat all manuscript sections equally, allowing background text to rank as highly as experimental results. To focus model outputs on experimentally supported responses, we developed the T21 Research Assistant, a section-aware RAG system that prioritizes Results sections to ground responses in primary experimental evidence. The system draws exclusively from 1,789 open-access Down syndrome publications from PubMed Central, including 327 NIH INCLUDE-funded studies, and uses a multistage pipeline for query validation, retrieval, reranking, synthesis, and citation verification. Built on NVIDIA Nemotron models, it generates structured, cited responses. Evaluation using expert-curated questions demonstrated strong performance, achieving a BERTScore F1 of 0.712 and recall of 0.758, comparable to or exceeding leading proprietary and open-source models. T21 Research Assistant is available at: https://bioinformatics.cuanschutz.edu/t21-res-assi/.

RASopathies are a group of developmental disorders caused by variations in genes of the RAS/mitogen activated protein kinase (MAPK) pathway and affect 1 in 1000 individuals worldwide. Due to overlapping clinical features, accurate diagnosis is challenging and therefore we used next-generation sequencing (NGS) panels as an effective molecular diagnostic tool. Targeted sequencing was performed on 130 samples using a multigene panel comprising of 21 RASopathy genes. Molecular analysis revealed variations in 74 individuals (57%). Pathogenic or likely pathogenic variations were observed in 60/74 (81%) of the cases, 13 (17.5%) had variant(s) of uncertain significance (VUS), and one novel variant was identified in RASA2 whose pathogenicity has not yet been established. In individuals with Noonan Syndrome, pathogenic variants were identified in eight different genes mainly PTPN11, SOS1, RAF1 and LZTR1. Nine clinically diagnosed Cardio-facio-cutaneous syndrome cases harboured variations in BRAF, MAP2K2 and MAP2K1 The c.34G>A variant in HRAS was seen in all nine individuals diagnosed with Costello syndrome. This study provides a comprehensive molecular and clinical profile of the largest Indian RASopathy cohort. The use of targeted gene panel has increased the variation detection rate in affected individuals.