Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders caused by enzyme deficiencies required for cortisol biosynthesis in the adrenal cortex. The majority of CAH are due to the deficiency of the 21-hydroxylase enzyme, while 3β-hydroxysteroid dehydrogenase type 2 deficiency accounts for less than five percent of all CAH cases. We report two Moroccan twins from a spontaneous triplet pregnancy. The 46,XY newborn exhibited a disorder of sexual differentiation (DSD) with hypo virilization, while the 46,XX newborn had normal female external genitalia. In the first week of life, they showed hyponatremia and primary adrenal insufficiency with a slight 17OHP elevation and increased DHEAS and renin levels. The aCGH-SNP analysis disclosed a 8.36 Mb long contiguous stretch of homozygosity (LCSH) on chromosome 1p13.2-p11.2 including the candidate HSD3B2 gene, a LCSH of 7.3 Mb on 14q31.1-q32.11, and a 7 Mb duplication on 10q22.3-q23.2. Clinical exome sequencing revealed the biallelic c.969T > G (p.Asn323Lys) HSD3B2, likely pathogenic, variant in both of the affected twins. This case emphasizes the importance of a prompt molecular diagnosis performed through the combination of aCGH and clinical exome, both for establishment of correct therapy and for follow-up, as the newborns also carry a genomic rearrangement with possible clinical implications.

Background and Objectives: Pediatric cardiovascular risk factors tend to track into adulthood, accelerating the atherosclerotic process. This study aimed to assess the prevalence of cardiometabolic risk factors, integrating anthropometric parameters, central adiposity indices, early growth trajectories, family history, and household lifestyle, in a primary-care pediatric cohort (the RISCAPED study). Materials and Methods: A cross-sectional multicenter study was conducted across primary care pediatric practices in the province of Alessandria, Northwest Italy, enrolling children aged 6 to 12 years. Weight status was classified according to World Health Organization 2007 criteria, abdominal adiposity by Waist-to-Height Ratio (WHtR > 0.5), and high blood pressure according to American Academy of Pediatrics percentiles (≥95th percentile). Family lifestyle habits were evaluated via the Family Nutrition and Physical Activity (FNPA) screening tool. Factors independently associated with high blood pressure and excess weight were identified using multivariable logistic regression models. Results: Among 479 children with complete anthropometric data (median age: 9.0 years), 42.3% presented with excess weight (21.9% overweight, 20.4% obesity). WHtR increased significantly across weight groups (median 0.44, 0.46 and 0.50, respectively; p < 0.001). Previously undiagnosed high blood pressurewas identified in 7.1% of the cohort, with a significant systolic blood pressure gradient (p < 0.001). Rapid weight gain during early infancy was significantly more frequent in children with obesity (10.6% vs. <5.3%, p = 0.025). In multivariable models, a family history of thrombophilic disorders (OR 3.16, 95% CI 1.27–7.41) and a less favourable FNPA score (OR 0.94 per point, 0.89–0.99) were independently associated with high blood pressure; a family history of hyperglycemia was associated overweight/obesity (OR 1.71, 1.06–2.78), and a family history of obesity wa associated with childhood obesity (OR 1.71, 1.02–2.88). Conclusions: Cardiovascular risk factors emerge early during primary school age, with central adiposity and silent high blood pressure manifesting prior to clinical disease. Multi-generational family history emerged as a consistent marker of risk, supporting routine multi-domain cardiovascular screening in primary pediatric healthcare.