Acinar dysplasia (AcDys) is one of the three main diffuse developmental disorders of the lung. The transcription factor NK2 homeobox 1 (NKX2.1) partly controls the synthesis of surfactant proteins by type 2 alveolar epithelial cells (AEC2), and germline mutations are known to be associated with brain-lung thyroid syndrome. We report the case of a full-term neonate who developed refractory respiratory failure with pulmonary hypertension requiring venoarterial extracorporeal membrane oxygenation. Histological examination of the lung biopsy specimen was consistent with the diagnosis of AcDys. Molecular analyses led to the identification of the missense heterozygous variant in NKX2.1 (NM_001079668) c.731A>G p.(Tyr244Cys), which is predicted to be pathogenic. After 5 weeks, because AcDys is a fatal disorder and the patient's status worsened, life-sustaining therapies were withdrawn, and she died after a few hours. This study is the first to extend the phenotype of NKX2.1 pathogenic variant, to a fatal form of AcDys.

中文翻译：

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NKX2.1 变异足月新生儿的腺泡发育不良。

腺泡发育不良（AcDys）是肺部三种主要弥漫性发育障碍之一。转录因子 NK2 同源框 1 (NKX2.1) 部分控制 2 型肺泡上皮细胞 (AEC2) 的表面活性蛋白合成，已知种系突变与脑肺甲状腺综合征相关。我们报告了一名足月新生儿的病例，该新生儿出现难治性呼吸衰竭并伴有肺动脉高压，需要静脉动脉体外膜氧合。肺活检标本的组织学检查与AcDys的诊断一致。分子分析鉴定出 NKX2.1 (NM_001079668) c.731A>G p.(Tyr244Cys) 中的错义杂合变体，预计该变体具有致病性。5周后，由于AcDys是一种致命性疾病，患者的病情恶化，维持生命的治疗被取消，几小时后她就去世了。这项研究首次将 NKX2.1 致病变异的表型扩展到 AcDys 的致命形式。