Characterization of the anterior segment in Trisomy 21-associated cataract using ultrasound biomicroscopy.

Backgroundobjectives: To compare the structural anatomy of the anterior segment in pediatric Trisomy 21 (T21) subjects with and without cataracts to age-matched controls. Design: Prospective case-control study. Participants: 40 subjects (57 eyes) age 0-25 years old (9.1 ± 10.6 years). Methods: This prospective case-control study evaluated anterior segment measurements from ultrasound biomicroscopy (UBM) imaging on 342 images. Results: Among persons with T21 cataract, the iris was significantly thinner than T21 individuals without cataract (0.28 vs 0.32 mm, p = 0.0181). T21/cataract subjects also had significantly thinner lenses than subjects without cataract, regardless of whether they have T21 or are controls (3.1 mm vs 3.5 mm, p = 0.0074).Thinner lens (<3.5 mm) was insignificantly associated with increased odds of cataract (OR = 9.5 [0.872,104], p = 0.065). Thinner iris (<0.32 mm) was associated with increased odds of cataract (OR = 8.4 [1.188, 59.273], p = 0.033). Conclusions: These findings support the hypothesis that subtle quantitative anatomic variants are present in the anterior eye of individuals with T21. Specific anatomic variants are unique to the presence of cataract among subjects with T21.

Performance analysis of non-invasive prenatal testing for trisomy 13, 18, and 21: A large-scale retrospective study (2018-2021).

Background: Non-invasive prenatal tests (NIPT) are used to screen for trisomy 21, 18, and 13. This study investigated NIPT performance and the clinical significance of its results. Methods: Pregnant women (n = 282,911) participating in a free NIPT (April 2018-December 2021) were screened for common trisomies, and the results were retrospectively analyzed. NIPT performance was evaluated by its positive predictive value (PPV), sensitivity, and specificity. Results were analyzed using number, percentage, and chi-squared/t-test analyses. Results: After NIPT screening, patients with common trisomies (n = 746) included 457 with T21, 160 with T18, and 129 with T13. Seven false negative cases were identified. High PPV (86.81 %, 56.81 %, 18.18 %), sensitivity (99.25 %, 98.33 %, 100.00 %), and specificity (99.98 %, 99.98 %, 99.97 %) values were detected for trisomy 21, 18, and 13, respectively. The PPVs of common trisomies were significantly different between pregnant women older than 35 (85.53 %, 136/159) and those aged 35 or younger (58.90 %, 311/528) (χ2 = 125.02, P = 2.20e-16). As the NIPT uptake increased from 2018 to 2021, live-born birth defect incidence decreased. Conclusion: NIPT performed well in screening for T21, T18, and T13. Our discoveries offer an important and useful guideline in laboratory and clinical genetic counseling.

Infertility following trisomic pregnancies: A nationwide cohort study.

OBJECTIVE: To study whether gynecologic or reproductive disorders show association with trisomic conceptions. METHODS: This nationwide cohort study utilized the Registry of Congenital Malformations to identify women who had a trisomic pregnancy (n = 5784), either with trisomy 13 (T13; n = 351), trisomy 18 (T18; n = 1065) or trisomy 21 (T21; n = 4369) from 1987 to 2018. We used the Finnish Maternity cohort to match the cases to population controls (n = 34 422) on the age, residence, and timing of pregnancy. These data were cross-linked to the ICD-10 diagnoses of the national Care Registry for Health Care data on specialized health care in Finland during 1996 to 2019. Both inflammatory (ICD-10 diagnoses: N70-N77) and noninflammatory disorders of the genital tract (N80-N98) were studied. Crude odds ratios (ORs) with 95% CIs were calculated for associations between diagnoses and trisomic conceptions. RESULTS: The diagnosis of female infertility (N97) at any time was associated with trisomic conceptions (OR: 1.19, 95% CI: 1.08-1.32). In the subgroup analysis, this association was found for T18 (OR: 1.29, 95% CI: 1.03-1.61) and T21 (OR: 1.17, 95% CI: 1.04-1.32), but not for T13 (OR: 1.15, 95% CI: 0.75-1.72). When restricting the timing of the diagnosis of female infertility, an elevated OR was found only after the index pregnancy (OR: 1.81, 95% CI: 1.56-2.09). These increased odds for infertility after trisomic conceptions were observed both in women <35 years (T18 OR: 1.91, 95% CI: 1.21-3.00; T21 OR: 1.68, 95% CI: 1.31-2.14) and in women ≥35 years (T18 OR: 2.17, 95% CI: 1.40-3.33; T21 OR: 1.87; 95% CI: 1.47-2.39), but not after T13 conceptions. CONCLUSION: Our observational data suggest a link between trisomic conceptions and subsequent diagnoses of infertility but do not demonstrate causality. These data implicate that partially similar mechanisms might predispose to trisomy and infertility, regardless of maternal age.

Low-level mosaic trisomy 7 at amniocentesis in a pregnancy associated with cytogenetic discrepancy between cultured amniocytes and uncultured amniocytes, perinatal progressive decrease of the trisomy 7 cell line and a favorable fetal outcome.

OBJECTIVE: We present low-level mosaic trisomy at amniocentesis in a pregnancy associated with cytogenetic discrepancy between cultured amniocytes and uncultured amniocytes, perinatal progressive decrease of the trisomy 7 cell line and a favorable fetal outcome. CASE REPORT: A 40-year-old, primigravid woman underwent amniocentesis at 16 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype of 46,XY in cultured amniocytes. Simultaneous array comparative genomic hybridization (aCGH) analysis on the DNA extracted from uncultured amniocytes revealed the result of arr (7) × 2-3, (X,Y) × 1, consistent with 24% mosaicism for trisomy 7. Polymorphic DNA marker analysis on the DNA extracted from the uncultured amniocytes and parental bloods excluded uniparental disomy (UPD) 7. Prenatal ultrasound findings were normal. She was referred for genetic counseling at 19 weeks of gestation. No repeat amniocentesis was suggested, and continuing the pregnancy was advised. At 22 weeks of gestation, the result of soluble fms-like tyrosine kinase-1 (sFlt-1)/placental growth factor (PlGF) = 6.1 (normal < 38). She did not have preeclampsia. At 39 weeks of gestation, a 3346-g male baby was delivered without any phenotypic abnormality. aCGH analysis on the DNA extracted from cord blood and placenta revealed the result of arr (1-22) × 2, (X,Y) × 1 with no genomic imbalance in all tissues. When follow-up at age three months, the baby was normal in development and phenotype. The peripheral blood had a karyotype of 46,XY, and interphase fluorescence in situ hybridization (FISH) analysis using the bacterial artificial chromosome (BAC) probes of chromosome 7 showed disomy 7 cells in all 102/102 cells. CONCLUSION: Low-level mosaic trisomy 7 at amniocentesis can be associated with cytogenetic discrepancy between cultured amniocytes and uncultured amniocytes, perinatal progressive decrease of the trisomy 7 cell line and a favorable fetal outcome.

Trisomy 21 with Maternally Inherited Balanced Translocation (15q;22q) in a Female Fetus: A Rare Case of Probable Interchromosomal Effect.

Chromosomal rearrangements can interfere with the disjunction and segregation of other chromosome pairs not involved in the rearrangements, promoting the occurrence of numerical abnormalities in resulting gametes and predisposition to trisomy in offspring. This phenomenon of interference is known as the interchromosomal effect (ICE). Here we report a prenatal case potentially generated by ICE. The first-trimester screening ultrasound of the pregnant woman was normal, but the NIPT indicated a high risk for three copies of chromosome 21, thus suspecting trisomy 21 (T21). After a comprehensive clinical evaluation and genetic counseling, the couple decided to undergo amniocentesis. The prenatal karyotype confirmed T21 but also showed a balanced translocation between the long arm of chromosome 15 (q22) and the long arm of chromosome 22. The parents' karyotypes also showed that the mother had the 15;22 translocation. We reviewed T21 screening methods, and we performed a literature review on ICE, a generally overlooked phenomenon. We observed that ours is the first report of a prenatal case potentially due to ICE derived from the mother. The recurrence risk of aneuploidy in the offspring of translocated individuals is likely slightly increased, but it is not possible to estimate to what extent. In addition to supporting observations, there are still open questions such as, how frequent is ICE? How much is the aneuploidy risk altered by ICE?

Prevalence, diagnostic features, and medical outcomes of females with Turner syndrome with a trisomy X cell line (45,X/47,XXX): Results from the InsighTS Registry.

Turner syndrome (TS) is defined by partial or complete absence of a sex chromosome. Little is known about the phenotype of individuals with TS mosaic with trisomy X (45,X/47,XXX or 45,X/46,XX/47,XXX) (~3% of TS). We compared the diagnostic, perinatal, medical, and neurodevelopmental comorbidities of mosaic 45,X/47,XXX (n = 35, 9.4%) with nonmosaic 45,X (n = 142) and mosaic 45,X/46,XX (n = 66). Females with 45,X/47,XXX had fewer neonatal concerns and lower prevalence of several TS-related diagnoses compared with 45,X; however the prevalence of neurodevelopmental and psychiatric diagnoses were not different. Compared to females with 45,X/46,XX, the 45,X/47,XXX group was significantly more likely to have structural renal anomalies (18% vs. 3%; p = 0.03). They were twice as likely to have congenital heart disease (32% vs. 15%, p = 0.08) and less likely to experience spontaneous menarche (46% vs. 75% of those over age 10, p = 0.06), although not statistically significant. Congenital anomalies, hypertension, and hearing loss were primarily attributable to a higher proportion of 45,X cells, while preserved ovarian function was most associated with a higher proportion of 46,XX cells. In this large TS cohort, 45,X/47,XXX was more common than previously reported, individuals were phenotypically less affected than those with 45,X, but did have trends for several more TS-related diagnoses than individuals with 45,X/46,XX.

Bruxism in a Child with Trisomy 21 (Down Syndrome)-Case Report.

Bruxism has been defined in recent years and analyzed in detail as the repetitive activity of the muscles of the masticatory system. Both adults and children experience two different forms of bruxism: daytime and nighttime bruxism. According to the WHO, bruxism affects 5% to 50% of the world's pediatric population. The symptoms of this disease include tooth wear and fractures, temporomandibular disorders, headaches, behavioral and sleep disorders, and parafunctional habits such as nail biting. According to scientists, psychosocial factors are the most likely factors causing bruxism in children. To this day, we do not have established standards of treatment for children, especially for those with disabilities. The issue of bruxism in children with Down syndrome (DS) is still unexplained. Anatomical abnormalities in the facial skeleton, reduced muscle tone, personality traits, and sleep problems in these people may cause the symptoms of bruxism. Our study aimed to present a clinical case of a 13-year-old girl with DS and symptoms of bruxism. Diagnostics and dental examination in children with intellectual disabilities and a lack of understanding of the disease create a great challenge for the treatment team, including the dentist, physiotherapist, psychologist, and family. Creating standards for treating and preventing bruxism symptoms is demanding, among other things, due to the lack of sufficient scientific research.

Craniofacial and Airway Morphology in Down Syndrome: A Cone Beam Computed Tomography Case Series Evaluation.

Background: Down syndrome (DS) is a genetic condition characterized by an extra copy of chromosome 21, resulting in various physical and cognitive features. This study aimed to comprehensively analyze the dental and craniofacial morphology of individuals with DS using Cone Beam Computed Tomography (CBCT). Methods: Six individuals with DS, comprising five males and one female aged 17 to 35 years, underwent CBCT scanning. Radiographic assessments included dentition, occlusion, paranasal sinuses, airway, skull bones, and suture calcification. Linear and angular cephalometric measurements were performed, and airway analysis was conducted using Dolphin 3D imaging software v.11. Results: The study revealed prognathic maxilla in five patients, prognathic mandible in four, and bimaxillary protrusion in two. Dental findings included microdontia, enamel hypoplasia, and congenitally missing teeth, with maxillary and mandibular third molars most commonly absent. Sinus abnormalities, delayed suture closure, and cervical spine anomalies were also observed. Conclusion: These findings contribute to a deeper understanding of DS-related craniofacial characteristics and emphasize the importance of considering these morphometric features in clinical management strategies for individuals with DS. This study's limited sample size underscores the significance of radiographic assessment in planning interventions such as cosmetic reconstructions, prosthetic rehabilitation, or orthodontic treatment for individuals with DS.

Internalizing Psychiatric Symptoms in People with Mosaicism for Trisomy 21.

People with mosaicism for trisomy 21 have been shown to exhibit the many of same phenotypic traits present in people with non-mosaic Down syndrome, but with varying symptom severity. However, the behavioral phenotype of people with mosaic Down syndrome (mDS) has not been well characterized. This study aimed to examine the prevalence of self-report and caregiver-report symptoms of depression and anxiety among a sample of 62 participants with mDS aged 12 - 46, and assess their association with the percentage of trisomy 21 in blood and/or buccal mucosa cells. The results showed that 53% of the participants reported clinically significant depression symptoms and 76% reported clinically significant anxiety symptoms. No clear associations were observed between the percentage of trisomic cells and total anxiety or depression, but a significant positive association between the proband-reported specific fears subscale and the percentage of trisomic cells in buccal specimens was detected (r = .43, p = .007). This study highlights the high occurrence of depression and anxiety symptoms in individuals with mDS and the need for routine assessment to optimize their care. It also demonstrates the ability of people with mDS to complete these evaluations, thereby supporting their inclusion in research studies/clinical trials.

Guideline for treating relapsed or refractory myeloid leukemia in children with Down syndrome.

Treatment of relapsed and refractory myeloid leukemia in Down syndrome (r/r ML-DS) poses significant challenges, as prognosis is dire and there is no established standard treatment. This guideline provides treatment recommendations based on a literature review and collection of expert opinions, aiming to improve overall and event-free survival of patients. Treatment options include fludarabine and cytarabine (FLA) ± gemtuzumab ozogamicin (GO), azacytidine (AZA) ± panobinostat, and hematopoietic stem cell transplantation (HSCT). Preferred approaches are AZA ± panobinostat for cases with low blast count or FLA ± GO for cases with high blast count, followed by HSCT after remission. Further research is crucial for the investigation of targeted therapies (e.g., BH3 mimetics, LSD1, JAK inhibitors).

Discordant Prenatal Cell-Free DNA Screening vs. Diagnostic Results of Sex Chromosome Aneuploidies: Implications for Newborn Screening and Genetic Counseling.

Sex chromosome aneuploidies (SCAs) collectively occur in 1 in 500 livebirths, and diagnoses in the neonatal period are increasing with advancements in prenatal and early genetic testing. Inevitably, SCA will be identified on either routine prenatal or newborn screening in the near future. Tetrasomy SCAs are rare, manifesting more significant phenotypes compared to trisomies. Prenatal cell-free DNA (cfDNA) screening has been demonstrated to have relatively poor positive predictive values (PPV) in SCAs, directing genetic counseling discussions towards false-positive likelihood rather than thoroughly addressing all possible outcomes and phenotypes, respectively. The eXtraordinarY Babies study is a natural history study of children prenatally identified with SCAs, and it developed a longitudinal data resource and common data elements with the Newborn Screening Translational Research Network (NBSTRN). A review of cfDNA and diagnostic reports from participants identified a higher than anticipated rate of discordance. The aims of this project are to (1) compare our findings to outcomes from a regional clinical cytogenetic laboratory and (2) describe discordant outcomes from both samples. Twenty-one (10%), and seven (8.3%) cases were found to be discordant between cfDNA (result or indication reported to lab) and diagnosis for the Babies Study and regional laboratory, respectively. Discordant results represented six distinct discordance categories when comparing cfDNA to diagnostic results, with the largest groups being Trisomy cfDNA vs. Tetrasomy diagnosis (66.7% of discordance in eXtraordinarY Babies study) and Mosaicism (57.1% in regional laboratory). Traditional genetic counseling for SCA-related cfDNA results is inadequate given a high degree of discordance that jeopardizes the accuracy of the information discussed and informed decision making following prenatal genetic counseling.

Corrigendum: One-carbon pathway metabolites are altered in the plasma of subjects with Down syndrome: relation to chromosomal dosage.

[This corrects the article DOI: 10.3389/fmed.2022.1006891.].

Management and Outcomes of Hepatoblastoma in Patients With Trisomy 18: A Systematic Review and Pooled Analysis of 70 Patients.

INTRODUCTION: Predicted 1-year survival of children with trisomy 18 (T18) has increased to 59.3%. We aimed to systematically review the characteristics, management, and outcomes of children with T18 and hepatoblastoma. METHODS: A systematic literature review of the PubMed, Embase, Scopus, Web of Science, and Cochrane Library databases was performed according to the PRISMA 2020 statement (end-of-search date: 03/03/2024). RESULTS: Fifty studies reporting on 70 patients were included. The median age at diagnosis was 11.5 months, 85.9% were female (n = 55/64), and 15.0% had mosaic T18 (n = 6/40). Diagnosis was made during symptom evaluation (most commonly hepatomegaly or abdominal mass) in 45.5% (n = 15/33), incidentally in 24.2% (n = 8/33), during surveillance with abdominal ultrasound in 18.2% (n = 6/33), and at autopsy in 12.1% (n = 4/33). The median tumor size was 6.4 cm, 33.3% had multiple tumors (n = 14/42), and metastasis was present in one patient (3.8%; n = 1/26). Neoadjuvant chemotherapy was administered in 42.6% (n = 26/61) and adjuvant chemotherapy in 31.6% (n = 18/57). Surgical treatment was performed in 64.2% (n = 43/67). Of the patients not diagnosed on autopsy, overall mortality was 35.5% (n = 22/62) over a median follow-up of 11.0 months. Among the 26 deceased patients (including those diagnosed on autopsy), the most common causes of death were cardiopulmonary disease (38.5%, n = 10/26) and tumor progression (30.8%, n = 8/26). CONCLUSIONS: T18 does not preclude resection with curative intent for hepatoblastoma. Combination of surgery and chemotherapy should be considered in children on an individualized basis depending on tumor characteristics and underlying cardiopulmonary comorbidities. Locoregional modalities may have a role in the setting of severe comorbidities. LEVEL OF EVIDENCE: Level IV evidence.

Practicalities (and real-life experiences) of dementia in adults with Down syndrome.

Adults with down syndrome (DS) have a lifetime dementia risk in excess of 95%, with a median age of onset of 55 years, due to trisomy 21. Co-occurring Alzheimer's disease (AD) has increased morbidity and mortality, and it is now recommended to screen for AD in all adults with DS beginning at 40 years of age. In this manuscript, we present two clinical cases of adults with DS who developed AD summarizing their medical histories, presenting symptoms, path to diagnosis and psychosocial aspects of care collected from retrospective chart review with caregiver consent. These two cases were chosen due to their complexity and interwoven nature of the medical and psychosocial aspects, and highlight the complexity and nuance of caring for patients with DS and AD.

Orthodontic findings in adults with Trisomy 21.

OBJECTIVES: Objective of this study was to describe orthodontic findings in adults with Down's syndrome, a matter insufficiently regarded in literature. MATERIALS AND METHODS: A group of 104 adults (33.8 ± 15 years) with trisomy 21 had an orthodontic check-up in their accustomed environment. Anamnestic and dental findings completed the examination and descriptive analysis was performed using SPSS23. Relative frequencies with 95% confidence intervals were compared to the average population (SHIP-study, 2003; DMS IV, 2006). RESULTS: Among the participants 46.2% (36.3-56.2%) (SHIP 36.7%) had already undergone orthodontic treatment. In 87.5% (79.6-93%) of the patients, less than 25.6 properly functioning permanent teeth (DMS IV's mean) were found. Gingival bleeding and recessions, as well as periodontal disease, were increasingly found in older affected persons. Patients with Down's syndrome showed less crowding, e.g., maxillary incisors 28% (19.3-39%) versus 41.9% (SHIP). Frontal open bite (35.2% (25.3-46.1%) versus 3.6% (SHIP)) and frontal crossbite (40.9% (30.5-51.9%) versus 4.2% (SHIP)) were more often observed. No considerable differences in frequencies of orthodontic findings were detected in the comparison of the subgroups "18-28 years" versus ">28 years", "with" versus "without orthodontic treatment", "male" versus "female", "with" versus "without periodontal problems", or "with" versus "without orofacial disturbances". CONCLUSIONS: Within the bounds of this study, we gathered orthodontic findings in adults with trisomy 21 for the first time. In comparison to the average population, the subject group showed a greater number of complex orthodontic findings. CLINICAL RELEVANCE: These persisting dental and orofacial problems must be considered when treating patients with Down's syndrome.

Hippocampal CA1 Pyramidal Neurons Display Sublayer and Circuitry Dependent Degenerative Expression Profiles in Aged Female Down Syndrome Mice.

Background: Individuals with Down syndrome (DS) have intellectual disability and develop Alzheimer's disease (AD) pathology during midlife, particularly in the hippocampal component of the medial temporal lobe memory circuit. However, molecular and cellular mechanisms underlying selective vulnerability of hippocampal CA1 neurons remains a major knowledge gap during DS/AD onset. This is compounded by evidence showing spatial (e.g., deep versus superficial) localization of pyramidal neurons (PNs) has profound effects on activity and innervation within the CA1 region. Objective: We investigated whether there is a spatial profiling difference in CA1 PNs in an aged female DS/AD mouse model. We posit dysfunction may be dependent on spatial localization and innervation patterns within discrete CA1 subfields. Methods: Laser capture microdissection was performed on trisomic CA1 PNs in an established mouse model of DS/AD compared to disomic controls, isolating the entire CA1 pyramidal neuron layer and sublayer microisolations of deep and superficial PNs from the distal CA1 (CA1a) region. Results: RNA sequencing and bioinformatic inquiry revealed dysregulation of CA1 PNs based on spatial location and innervation patterns. The entire CA1 region displayed the most differentially expressed genes (DEGs) in trisomic mice reflecting innate DS vulnerability, while trisomic CA1a deep PNs exhibited fewer but more physiologically relevant DEGs, as evidenced by bioinformatic inquiry. Conclusions: CA1a deep neurons displayed numerous DEGs linked to cognitive functions whereas CA1a superficial neurons, with approximately equal numbers of DEGs, were not linked to pathways of dysregulation, suggesting the spatial location of vulnerable CA1 PNs plays an important role in circuit dissolution.

Re-Examination of PGT-A Detected Genetic Pathology in Compartments of Human Blastocysts: A Series of 23 Cases.

Background: In recent years, preimplantation genetic testing for aneuploidies (PGT-A) has become widespread in assisted reproduction. However, contrary to expectations, PGT-A does not significantly improve the clinical outcomes of assisted reproductive technologies. One of the underlying reasons is the discordance between the PGT-A results and the true chromosomal constitution of the blastocyst. In this case series, we re-examined the PGT-A results in trophectoderm (TE) re-biopsies and in the two isolated blastocyst compartments-the TE and the inner cell mass (ICM). Methods: This study enrolled 23 human blastocysts from 17 couples who were referred for assisted reproduction. The blastocysts were unsuitable for uterine transfer due to the chromosomal imbalance revealed by PGT-A using array comparative genomic hybridization (aCGH) (n = 11) or next-generation sequencing (NGS) (n = 12). The re-examination of the PGT results involved two steps: (1) a TE re-biopsy with subsequent aCGH and (2) blastocyst separation into the TE and the ICM with a subsequent cell-by-cell analysis of each isolated compartment by fluorescence in situ hybridization (FISH) with the DNA probes to chromosomes 13, 16, 18, 21, and 22 as well as to the PGT-A detected imbalanced chromosomes. Results: In 8 out of 23 cases, the PGT-A results were concordant with both the re-biopsy and the isolated TE and ICM analyses. The latter included the diagnoses of full non-mosaic aneuploidies (five cases of trisomies and two cases of monosomies). In one case, the results of PGT-A, aCGH on the TE re-biopsy, and FISH on the isolated TE showed Xp tetrasomy, which contrasted with the FISH results on the isolated ICM, where this chromosomal pathology was not detected. This case was classified as a confined mosaicism. In 4 out of 23 cases, the results were partially discordant. The latter included one case of trisomy 12, which was detected as non-mosaic by PGT-A and the re-biopsy and as mosaic by FISH on the isolated TE and ICM. This case was classified as a true mosaicism with a false negative PGT-A result. In 11 out of 23 cases, the re-examination results were not concordant with the PGT-A results. In one of these discordant cases, non-mosaic tetraploidy was detected by FISH in the isolated TE and ICM, whereas the PGT-A and the TE re-biopsy failed to detect any abnormality, which advocated for their false negative result. In two cases, the re-examination did not confirm full aneuploidies. In eight cases, full or partial mosaic aneuploidies as well as chaotic mosacism were not confirmed in the isolated TE nor the isolated ICM. Thus, in 47.8% of cases, the PGT-A results did not reflect the true chromosomal constitution of a blastocyst. Conclusions: The PGT results may have different prognostic value in the characterization of the chromosomal constitution of a blastocyst. The detected non-mosaic aneuploidies have the highest prognostic value. In stark contrast, most PGT-identified mosaic aneuploidies fail to characterize the true chromosomal constitution of a blastocyst. Once detected, a differential diagnosis is needed.

Management and outcomes of congenital nasolacrimal duct obstruction in trisomy 21 patients vs. non-trisomy 21 patients within a paediatric population: a 5-year follow-up.

PURPOSE: To assess the management of patients with congenital nasolacrimal duct obstruction (CNLDO) in a paediatric population and review the long-term outcomes over a 5-year interval, with particular emphasis on the difference between patients with trisomy 21 and those without trisomy 21. METHODS: This single-centre, retrospective, cross-sectional, case review study included patients suffering from CNLDO at Alder Hey Children's Hospital NHS foundation Trust. Patients were divided into two groups: Non-trisomy 21 and trisomy 21. Patients were followed-up for a 60-month interval. Patients aged <12 months at the time of surgery, patients with <60 months of follow-up data and patients with acquired nasolacrimal duct obstruction were excluded. The main outcome measures were discharge rates in patients undertaking primary intervention with syringe and probe (S&P), number of patients requiring further treatment with lacrimal intubation or dacryocystorhinostomy (DCR) and overall symptom-free periods post-treatment. RESULTS: Ninety-three patients (142 eyes) were included. The mean number of surgical interventions was 1.53 ± 0.65. The mean interval between the 1st and 2nd intervention was 15.54 ± 16.33 months. There was a trend towards greater success rates non-trisomy 21 patients versus patients with trisomy 21 (p = 0.1352). The average symptom-free period after the final intervention was 44.31 ± 20.68 months, significantly longer in the non-trisomy 21 group compared to the trisomy 21 group (p = 0.0074). CONCLUSIONS: The overall success rate after primary S&P was 55.9%. Our results suggest that in trisomy 21 patients suffering from CNLDO, a one-stage intervention with primary monocanalicular intubation should be considered instead of sequential approach.

Chronic Ileum Obstruction, Granulation, and Ulceration With IgG4-Positive Plasma Cell Infiltration in a Six-Year-Old Girl With 21trisomy.

Patients with 21trisomy often develop congenital or acquired gastrointestinal diseases, such as duodenal or anal atresia, celiac disease, intussusception, and constipation. In these patients, it is often challenging to diagnose gastrointestinal diseases because most patients have difficulty explaining their complaints in detail. Furthermore, these patients also possess immunological disorders, such as increased type I interferon activation, innate immune hypersensitivity, and polarization to autoimmune. Here, we present a girl with 21trisomy and constipation who developed severe anemia, occult blood and elevated levels of calprotectin in stool, and chronic ileum obstruction confirmed by computed tomography. The patient underwent surgical resection of the ileum and recovered without complications. Pathological examination demonstrated intussusception, ischemia, ulceration, inflammatory granulation, and massive IgG4-positive plasma cell infiltration. After the surgery, her fecal calprotectin levels were normalized. We assumed that the ileum inflammation caused by ileum dilation generated ulcers and granulation, which could be associated with immunological, gastrointestinal, and intellectual disorders in patients with 21trisomy.