Jacobsen syndrome (JS) is a rare syndrome caused by a deletion of chromosome 11q. We report a patient with JS and hypoplastic left heart syndrome (HLHS) who required cardiac transplantation. She had many of the recognized morphological features in addition to immunological (lymphopenia) and hematological (thrombocytopenia) issues. The patient underwent a Norwood procedure with a modified Blalock–Taussig shunt (MBTS) and subsequently a Glenn procedure at six months of age. She developed desaturation, with severe tricuspid regurgitation and right ventricular dysfunction, and underwent heart transplantation at 7 months of age. After the transplant, she was hospitalized several times for severe infections. The diagnosis of Jacobsen syndrome came 2 months after transplant. Now, 5 years post-transplant, she is in relatively good health—her heart is functioning normally, her hospitalization rate is getting lower, and her immunological profile is stable.

Sotos syndrome is an autosomal dominant condition characterized by overgrowth with advanced bone age, macrodolicocephaly, motor developmental delays and learning difficulties, and characteristic facial features caused by heterozygous pathogenetic variants in the NSD1 gene located on chromosome 5q35. The prevalence of heart defects (HDs) in individuals with Sotos syndrome is estimated to be around 15–40%. Septal defects and patent ductus arteriosus are the most commonly diagnosed malformations, but complex defects have also been reported. The aim of our study was to analyze the prevalence of HD, the anatomic types, and the genetic characteristics of 45 patients with Sotos syndrome carrying pathogenetic variants of NSD1 or a 5q35 deletion encompassing NSD1, who were followed at Bambino Gesù Children’s Hospital in Rome. Thirty-nine of the forty-five patients (86.7%) had a mutation in NSD1, while six of the forty-five (13.3%) had a deletion. Most of the patients (62.2%, 28/45) were male, with a mean age of 14 ± 7 years (range 0.2–37 years). A total of 27/45 (60.0%) of the patients had heart defects, isolated or combined with other defects, including septal defects (12 patients), aortic anomalies (9 patients), mitral valve and/or tricuspid valve dysplasia/insufficiency (1 patient), patent ductus arteriosus (3 patients), left ventricular non-compaction/hypertrabeculated left ventricle (LV) (4 patients), aortic coarctation (1 patient), aortopulmonary window (1 patient), and pulmonary valve anomalies (3 patients). The prevalences of HD in the two subgroups (deletion versus intragenic mutation) were similar (66.7% (4/6) in the deletion group versus 58.91% (23/39) in the intragenic variant group). Our results showed a higher prevalence of HD in patients with Sotos syndrome in comparison to that described in the literature, with similar distributions of patients with mutated and deleted genes. An accurate and detailed echocardiogram should be performed in patients with Sotos syndrome at diagnosis, and a specific cardiological follow-up program is needed.

The "mediastinal syndrome" is an oncological urgency but, in some situations as in the case report described below, it can present itself in a subtle and inextricable way with symptoms and signs that, if singularly evaluated, can be nonspecific. In particular, we report the case of facial edema and a rash that, developing in an unusual and progressive way during about 2 months, concealed a voluminous mediastinal formation due to the localization of non-Hodgkin B-cell lymphoma that caused a "superior caval vein syndrome".