Severe Suprasystemic Refractory Pulmonary Hypertension in a Neonate with Stüve-Wiedemann Syndrome Associated with Biallelic LIFR Variants: Molecular Insights and a Neonatal Case Report.
Chojnacka K, Sibrecht G, Gruca-Stryjak K, Szczapa T • International journal of molecular sciences • 2026
A neonate with genetically confirmed Stüve-Wiedemann syndrome presented with severe suprasystemic persistent pulmonary hypertension of the newborn refractory to standard pulmonary vasodilators including inhaled nitric oxide, providing detailed longitudinal hemodynamic characterization of pulmonary vascular involvement in this ultra-rare disorder.
Key Findings
Background
Stüve-Wiedemann syndrome (SWS) is caused by loss-of-function variants in the leukemia inhibitory factor receptor (LIFR) gene and follows an autosomal recessive inheritance pattern.
SWS is classified as an ultra-rare autosomal recessive skeletal dysplasia.
The condition results from biallelic LIFR variants, as confirmed in the reported case.
Clinical features include bone deformities and dysautonomia.
Severe persistent pulmonary hypertension of the newborn (PPHN) significantly contributes to high early mortality in SWS.
Results
The reported neonate with SWS developed severe, suprasystemic PPHN that was refractory to standard pulmonary vasodilator therapies.
The PPHN was classified as suprasystemic, meaning pulmonary arterial pressures exceeded systemic arterial pressures.
The neonate did not respond adequately to inhaled nitric oxide, a standard first-line pulmonary vasodilator.
The case represents genetically confirmed SWS with molecular characterization of LIFR variants.
The PPHN was described as refractory to standard pulmonary vasodilators.
Results
The case provides a detailed longitudinal hemodynamic characterization of PPHN in SWS, including serial assessment of pulmonary pressures, shunt direction, and right ventricular function during treatment.
Serial echocardiographic assessments were performed to monitor pulmonary pressures over time.
Shunt direction was assessed longitudinally during the treatment course.
Right ventricular function was evaluated serially during treatment.
This characterization extends the phenotypic and hemodynamic description of pulmonary vascular involvement in SWS rather than identifying PPHN as a novel manifestation.
Discussion
The paper provides molecular insights into how LIFR pathway disruption may contribute to pulmonary vascular disease in SWS.
LIFR encodes the leukemia inhibitory factor receptor, a cytokine receptor involved in multiple signaling pathways.
Loss-of-function variants in LIFR are proposed to underlie the pulmonary vascular phenotype observed in SWS.
The molecular analysis focused on biallelic LIFR variants identified in the proband.
The paper frames the pulmonary hypertension within the context of LIFR signaling disruption as a mechanistic consideration.
Conclusions
PPHN in SWS represents a significant contributor to the high early mortality associated with this syndrome.
Severe PPHN is identified as a major factor in early neonatal death in SWS.
The refractory nature of PPHN to conventional therapies in this case illustrates the clinical challenge posed by pulmonary vascular involvement in SWS.
The case extends phenotypic characterization of SWS to include detailed hemodynamic data on pulmonary vascular disease.
The authors frame the report as extending rather than newly identifying pulmonary hypertension as part of the SWS phenotype.
What This Means
This research describes a newborn baby diagnosed with Stüve-Wiedemann syndrome (SWS), an extremely rare genetic disorder caused by mutations in both copies of the LIFR gene. The baby developed a life-threatening condition called severe suprasystemic persistent pulmonary hypertension of the newborn (PPHN), where blood pressure in the lungs rose so high it exceeded the pressure in the rest of the body. Standard treatments, including a common therapy called inhaled nitric oxide that helps relax lung blood vessels, did not adequately control the condition. The doctors performed repeated heart ultrasounds over time to carefully track how lung pressures, blood flow patterns, and heart function changed during treatment.
The paper also explores the molecular biology behind why LIFR gene mutations might cause such severe lung blood vessel problems. The LIFR protein is part of a signaling system that affects many body functions, and when it does not work properly, it appears to contribute to abnormal development or function of the blood vessels in the lungs. This research suggests that pulmonary hypertension is an important and potentially underappreciated part of what makes SWS so dangerous in the newborn period, contributing significantly to the high rate of early death seen in this condition.
This research suggests that clinicians caring for newborns with SWS should be prepared for the possibility of severe and treatment-resistant pulmonary hypertension. By documenting the detailed course of hemodynamic changes in this confirmed genetic case, the authors provide a clearer picture of what pulmonary vascular disease looks like in SWS, which may help guide monitoring and treatment decisions in future cases of this ultra-rare syndrome.
Chojnacka K, Sibrecht G, Gruca-Stryjak K, Szczapa T. (2026). Severe Suprasystemic Refractory Pulmonary Hypertension in a Neonate with Stüve-Wiedemann Syndrome Associated with Biallelic LIFR Variants: Molecular Insights and a Neonatal Case Report.. International journal of molecular sciences. https://doi.org/10.3390/ijms27177824