We report a novel genetic variant in a patient with treatment-resistant peripheral pulmonary artery stenosis (PPS) and progressive pulmonary arterial hypertension (PAH). A premature infant was diagnosed with bilateral PPS requiring multiple surgical reconstructions and interventional procedures with refractory proximal stenoses. Despite adequate anatomic repair preserving nearly all right lung segments, the child developed progressive PAH with elevated pressures in preserved segments out of proportion to residual obstruction. Genetic evaluation revealed a de novo heterozygous variant in FGD5, a critical regulator of VEGF signaling essential for pulmonary vascular development and homeostasis. We propose that FGD5 haploinsufficiency could disrupt endothelial function during development, leading to aberrant vascular patterning. This dysfunction may lead to PPS and ongoing endothelial dysfunction contributing to PAH. This represents a potential novel genetic cause of PPS with PAH, expanding the understanding of critical regulators in pulmonary vascular development and pathology. Comprehensive genetic evaluation in treatment-resistant pulmonary vascular disease may identify novel mechanisms and eventually guide personalized therapeutic approaches through enhanced genotype-phenotype correlation.

Alagille syndrome is a rare multisystemic genetic condition most commonly associated with neonatal liver disease. Variable expressivity is a defining feature of Alagille syndrome, resulting in a broad spectrum of phenotypic variation among individuals who meet the diagnostic criteria. We present an atypical case of cardiac-predominant Alagille syndrome diagnosed in adulthood after the detection of peripheral pulmonary stenosis on cardiac magnetic resonance imaging (CMR).

Targeted neonatal echocardiography (TNE) is increasingly utilized by neonatologists to assess hemodynamics, particularly when cardiology-performed echocardiography (CPE) is unavailable. It is crucial that TNE screens and identifies structural abnormalities. This study evaluated the agreement between TNE and CPE in detecting significant congenital heart disease (CHD). This retrospective, single-center cohort study included infants who underwent TNE between 2015 and 2019 and had at least one complete CPE before discharge. Infants with a known CHD diagnosis prior to TNE were excluded. Atrial septal defects (ASD) < 3 mm, peripheral pulmonary stenosis, and patent ductus arteriosus were excluded. Agreement between TNE and CPE was assessed using correlation coefficients and kappa statistics. A total of 339 infants with 954 TNE scans were included. TNE identified CHD in 41 infants, with all but one (a false positive bicuspid aortic valve) confirmed by CPE. TNE missed CHD in 29 infants (31 lesions), mostly minor, with only one case (pulmonary stenosis) requiring intervention. The overall agreement was 91.15%, with a kappa of 0.68 (p < 0.0001). TNE demonstrated good agreement with CPE in detecting significant CHD in a low-risk neonatal population. Most missed lesions were minor, underscoring the importance of ongoing training and quality assurance.

Beaulieu-Boycott-Innes syndrome (BBIS) is a rare autosomal recessive neurodevelopmental disorder caused by THOC6 gene mutations. While BBIS typically presents with intellectual disability, dysmorphic features, and congenital anomalies, its association with ambiguous genitalia and disorders of sexual development has not been previously reported. Expanding the phenotypic spectrum is crucial for early diagnosis and management. A 35-day-old Palestinian infant presented with loud breathing sounds and cough. Examination revealed dysmorphic facial features, ambiguous genitalia, and anorectal malformation. Further evaluation identified bilateral inguinal gonads and congenital heart defects, including a ventricular septal defect, patent foramen ovale, and peripheral pulmonary stenosis. Chromosomal analysis showed a normal male karyotype (46, XY). Whole exome sequencing identified a novel homozygous splice site mutation in the THOC6 gene (c.155+1G>T), confirming the diagnosis of BBIS. Both parents were found to be heterozygous carriers. The patient underwent surgical correction of the anorectal malformation and received supportive care for respiratory infection. A multidisciplinary follow-up plan was initiated involving pediatrics, endocrinology, neurology, cardiology, and genetics. Postsurgical recovery was uneventful, but the patient exhibited growth retardation and developmental delay. Long-term monitoring is ongoing to assess neurodevelopmental progress and organ function. This case reports a novel presentation of BBIS associated with ambiguous genitalia, emphasizing the importance of considering THOC6 mutations in patients with syndromic features and congenital anomalies. Early genetic testing is vital for diagnosis and management planning.

Infectious endocarditis (IE) in patients with Williams syndrome is usually associated with left-sided heart lesions, whereas right-sided endocarditis is rarely observed. This can be explained by the natural course of congenital heart lesions in Williams syndrome, in which right-sided heart lesions are likely to spontaneously regress with patient growth. We encountered a 29-year-old patient diagnosed with right-sided infective endocarditis. His diagnosis was supported by the modified Duke criteria, one major criterion of positive blood culture twice with Streptococcus oralis, a type of gram-positive viridance Streptococcus, and three minor criteria of the presence of congenital heart disease, persistent fever higher than 38.0℃, and spatial and temporal dissemination of septic pulmonary emboli. Although his supravalvular aortic stenosis remained mild, peripheral pulmonary stenosis was progressive even after adulthood, which might have been attributed to the development of right-sided infectious endocarditis, based on the biased distribution of septic emboli. Severely advanced caries with extensive tooth decay were not diagnosed until the development of IE because of intellectual disability and inability to report subjective symptoms. The subsequent development of diverticulitis after the treatment of infectious endocarditis was difficult to diagnose, and the management of this patient became more complicated. As the disease-specific pathophysiology progresses with age and adult Williams syndrome patients are less likely to express subjective symptoms, a multidisciplinary approach by the medical team comprised of cardiologists, nephrologists, gastroenterologists, dentists, and psychologists is needed in the management of Williams syndrome, particularly in adults in the process of becoming independent.