Heterozygous FOXN1 Variants Cause Low TRECs and Severe T Cell Lymphopenia, Revealing a Crucial Role of FOXN1 in Supporting Early Thymopoiesis.

FOXN1 is the master regulatory gene of thymic epithelium development. FOXN1 deficiency leads to thymic aplasia, alopecia, and nail dystrophy, accounting for the nude/severe combined immunodeficiency (nu/SCID) phenotype in humans and mice. We identified several newborns with low levels of T cell receptor excision circles (TRECs) and T cell lymphopenia at birth, who carried heterozygous loss-of-function FOXN1 variants. Longitudinal analysis showed persistent T cell lymphopenia during infancy, often associated with nail dystrophy. Adult individuals with heterozygous FOXN1 variants had in most cases normal CD4+ but lower than normal CD8+ cell counts. We hypothesized a FOXN1 gene dosage effect on the function of thymic epithelial cells (TECs) and thymopoiesis and postulated that these effects would be more prominent early in life. To test this hypothesis, we analyzed TEC subset frequency and phenotype, early thymic progenitor (ETP) cell count, and expression of FOXN1 target genes (Ccl25, Cxcl12, Dll4, Scf, Psmb11, Prss16, and Cd83) in Foxn1nu/+ (nu/+) mice and age-matched wild-type (+/+) littermate controls. Both the frequency and the absolute count of ETP were significantly reduced in nu/+ mice up to 3 weeks of age. Analysis of the TEC compartment showed reduced expression of FOXN1 target genes and delayed maturation of the medullary TEC compartment in nu/+ mice. These observations establish a FOXN1 gene dosage effect on thymic function and identify FOXN1 haploinsufficiency as an important genetic determinant of T cell lymphopenia at birth.

Post-SARS-CoV-2 Atypical Inflammatory Syndrome in a Toddler with X-Linked Inhibitor of Apoptosis Deficiency After Stem Cell Transplant.

A 10-month-old boy was diagnosed with X-linked lymphoproliferative syndrome type 2 due to X-linked inhibitor of apoptosis deficiency after presenting with failure to thrive and refractory inflammatory bowel disease. He underwent a matched unrelated donor stem cell transplant with reduced intensity conditioning at 16 months. At 27 months, he presented with an atypical inflammatory syndrome in the setting of recent COVID-19 infection, Epstein-Barr viremia, and low chimerism (7.3%). He recovered after treatment with intravenous immunoglobulin and steroids.

Myofascial Closure of Intradural Inclusion Cysts following in utero Myelomeningocele Repair.

Myelomeningocele is one of the most common congenital malformations. A randomized controlled trial, known as the Management of Myelomeningocele Study (MOMS), demonstrated that closure during the fetal period can be performed relatively safely and be of significant benefit to patients. However, postnatally, patients can develop resultant symptoms from a tethered cord and inclusion cysts; this often requires surgical treatment. Repeat surgery in this population can be challenging due to the age of the patients, the extent of surgical exposure needed and the need for resection of dermal and epidermal tissues in the midline. We describe our approach for closure of these complex defects using lateral fasciocutaneous flaps with relaxing incisions made in the posterior axillary line, in order to minimize tension and maximize soft tissue coverage of the midline.

Successful Pregnancy Outcome in a Hereditary Angioedema Patient With Previous Pregnancy Losses: A Proposed Delivery Plan.

This case report underscores the effective implementation of a delivery plan for a pregnant patient, focusing on a successful case study where a cesarean section, preceded by the pre-treatment of intravenous plasma-derived C1 inhibitor, resulted in the delivery of a healthy baby. The proposed delivery plan offers a systematic approach to managing hereditary angioedema during pregnancy. It recommends opting for delivery at an academic center equipped with high-risk obstetric care, obstetric anesthesia, and a level 4 Neonatal Intensive Care Unit. The plan also emphasizes the importance of early admission at the onset of labor and delineates specific protocols for both vaginal and cesarean deliveries.

Video capsule endoscopy impacts decision making in pediatric IBD: a single tertiary care center experience.

BACKGROUND: Little is known about the impact of video capsule endoscopy (VCE) on decision making in pediatric patients with IBD. Moreover, few studies have reported on the outcomes of treatment changes made based on VCE findings. Our aim was to identify the added value of VCE in pediatric patients in a tertiary IBD center with established or suspected IBD, by assessing changes in treatments and outcomes before and after VCE. METHODS: A retrospective chart review was performed in children with established (n = 66) or suspected (n = 17) IBD who underwent VCE. Diagnostic classifications, treatments, and clinical outcomes before and 1 year after VCE were compared. RESULTS: Primary indications for VCE included patients treated for Crohn's disease (CD) with poor growth or active symptoms (60%), patients with ulcerative colitis/IBD-unclassified (19%), and suspected IBD (20%). Abnormal VCE was seen in 86% of patients with CD, of whom 75% underwent treatment escalation. One year after VCE, patients with CD improved in growth (mean z-scores at baseline and 12 months, -0.5 and 0.2, respectively; P < 0.0001), mean body mass index (18.3 and 19.8, respectively; P = 0.004), mean erythrocyte sedimentation rate (25 versus 16, respectively; P = 0.012), and median Harvey-Bradshaw Index (2 and 0, respectively; P = 0.003). VCE revealed more extensive disease than concurrent imaging modalities in 43% of the patients with CD. VCE "ruled out" IBD in 94% who had suspected IBD, whereas 50% with presumed ulcerative colitis/IBD-unclassified had a diagnosis changed to CD. CONCLUSIONS: VCE provides additional clinical information that impacted management of pediatric patients with IBD in a tertiary IBD center and was associated with improved outcomes.