Initial validation of the diagnostic performance of Thymic-Thoracic Ratio as a marker of conotruncal abnormalities and for prediction of surgical prognosis in fetuses without 22q11.2 deletion.

AIM: The present study aimed to perform an initial validation of the Thymic-Thoracic Ratio as a sonographic marker of conotruncal defects in non-syndromic fetuses and to assess the possible correlation between the grade of thymic hypoplasia and the severity of conotruncal defects. METHODS: The study was conducted between January and June 2018 on singleton pregnant women who underwent fetal echocardiography at our institution. Fetuses with a diagnosis of conotruncal defects without 22q11.2 deletion composed the study group, while healthy appropriate for gestational age fetuses composed the control group. The Thymic-Thoracic Ratio was measured in all included fetuses and compared between the study and control group. A ROC curve analysis to evaluate the diagnostic performance of Thymic-Thoracic Ratio toward the diagnosis of conotruncal defects was performed, with determination of sensitivity, specificity, PPV, NPV, positive likelihood ratio, and negative likelihood ratio. The severity of conotruncal defects was defined with the Aristotle score in each newborn who underwent a surgical operation. The correlation between Thymic-Thoracic Ratio and Aristotle score was assessed. RESULTS: During the study period, 23 fetuses with conotruncal defects without 22q11.2 deletion constituted the study group, and 67 healthy appropriate for gestational age fetuses were included in the control group. The T-T ratio of the study group was significantly lower than the control group (0.32 ± 0.08 vs. 0.41 ± 0.08, p < .001). The ROC curve analysis showed an AUC of 0.80 (95% CI, 0.71-0.89, p < .001) and a T-T ratio cutoff value of 0.35 for the identification of a CTD, with a sensibility of 73.9% (95% CI: 51.6-89.8%), a specificity of 79.1% (95% CI: 67.4-88.1%) a PPV of 54.8% (95% CI: 41.8-67.3%), a NPV of 89.8% (95% CI: 81.5-94.7), a positive likelihood ratio of 3.54 (95% CI 2.09-5.98), and a negative likelihood ratio of 0.33 (95% CI 0.16-0.66). A negative correlation between Aristotle score and T-T ratio was found, with a Kendall-Tau coefficient of -0.41, p = .04. CONCLUSION: T-T ratio measurement could be useful to identify fetuses at higher risk of conotruncal heart diseases, even without chromosomic deletion, with a cutoff of 0.35. Since a lower T-T ratio seems to be related to a worse surgical neonatal prognosis, it could be possible to provide effective counseling and refer patients to high-specialized centers for fetal echocardiography and cardiac surgery.

The Clinical Spectrum of Inflammatory Bowel Disease Associated With Specific Genetic Syndromes: Two Novel Pediatric Cases and a Systematic Review.

Background and Aims: Inflammatory bowel disease (IBD) is a typical polygenic disorder and less frequently shows a monogenic origin. Furthermore, IBD can originate in the context of specific genetic syndromes associated with a risk of autoimmune disorders. We aimed to systematically evaluate the prevalence of IBD in specific genetic syndromes and to review the clinical characteristics of the published cases. Methods: According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, studies describing patients with IBD and a genetic syndrome and/or studies indicating the prevalence or incidence of IBD in subjects with a genetic syndrome were included. Results: Forty-six studies describing a total of 67 cases of IBD in six genetic syndromes and two personally assessed unpublished cases were included in the review. The majority of cases were associated with Turner syndrome (TS) (38 cases), Down syndrome (DS) (18 cases) and neurofibromatosis type 1 (NF1) (8 cases). Sporadic cases were described in DiGeorge syndrome (2), Kabuki syndrome (2), and Williams syndrome (1). The prevalence of IBD ranged from 0.67 to 4% in TS and from 0.2 to 1.57% in DS. The incidence of IBD was increased in TS and DS compared to the general population. Eight cases of IBD in TS had a severe/lethal course, many of which described before the year 2000. Two IBD cases in DS were particularly severe. Conclusion: Evidence of a greater prevalence of IBD is accumulating in TS, DS, and NF1. Management of IBD in patients with these genetic conditions should consider the presence of comorbidities and possible drug toxicities. Systematic Review Registration: PROSPERO, identifier: CRD42021249820.