Abstract Beckwith-Wiedemann syndrome (BWS) is a congenital overgrowth disorder characterized by macrosomia, macroglossia, omphalocele, and predisposition to embryonal tumors. It is characterized by either gene duplication or genomic imprinting at 11p15 from a maternally derived gene. Clinical features are variable. However, pulmonary involvement is not typically recognized as a classic feature of this syndrome. We report a 33 week premature newborn, dichorionic diamniotic twin with respiratory distress requiring intubation and ventilatory support. The infant was noted to have a moderate omphalocele. Maternal history is complicated by gestational diabetes on insulin, preeclampsia with severe features, severe polyhydramnios, and IVF conception. Despite standard management for respiratory distress syndrome, the neonate had persistent respiratory distress and difficulty in weaning from mechanical ventilation for over 6 weeks. Meanwhile, a genetic workup confirmed the diagnosis of Beckwith-Wiedemann syndrome. However, given the unusually prolonged respiratory course, a chest CT was obtained, revealing findings of bilateral diffuse ground glass opacities suggesting possible surfactant deficiency. A further genetic analysis focused on surfactant deficiency panel was negative for common mutations and positive for a single SMAD9 gene mutation. The CT Angio ruled out arteriovascular malformation. Given the negative surfactant gene panel (aside from the SMAD9 variant of uncertain significance), the team faced the clinical dilemma of whether to consider an invasive lung biopsy for definitive diagnosis versus conservative management.The case represents a neonate with BWS and omphalocele, accompanied by a coexisting pulmonary disease process. While pulmonary involvement is not a recognized feature of BWS, rare case reports may mention pulmonary complications secondary to other features (e.g., macroglossia causing airway obstruction, omphalocele affecting respiratory mechanics, or prematurity-related respiratory issues). In this patient persistent respiratory failure and characteristic imaging findings raised suspicion for intrinsic lung pathology and genetic studies were negative except for a SMAD9 variant of uncertain significance; SMAD 9 is a downstream modulator of the bone morphogenetic protein signaling pathway which is a part of the TGF B superfamily. Although SMAD 9 mutation has been linked to primary pulmonary hypertension, the infant showed no evidence of it. Currently, the clinical team is considering whether pursuing a tissue diagnosis would change management and be possible due to the significant respiratory support the infant requires. The definitive diagnosis remains unclear. To date, there are no reported cases of BWS coexisting with intrinsic lung parenchymal disorders like surfactant-related diseases or diffuse lung disease, making this presentation particularly unique and diagnostically challenging. This abstract is funded by: None
Raj et al. (Fri,) studied this question.