Acinar Dysplasia in a Full-Term Newborn with a NKX2.1 Variant

Yohan Soreze (1) , Nadia Nathan (1, 2) , Julien Jegard (3) , Erik Hervieux (1) , Pauline Clermidi (1) , Chiara Sileo (1) , Camille Louvrier (1, 2) , Marie Legendre (1, 2) , Aurore Coulomb l'Herminé (1)

1 CHU Trousseau [APHP]
2 U933 - Maladies génétiques d'expression pédiatrique
3 CHU Nantes - Centre Hospitalier Universitaire de Nantes = Nantes University Hospital

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 After 5 weeks, because AcDys is a fatal disorder and the patient's status worsened, life-sustaining therapies were withdrawn, and she died after a few hours.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.

Keywords: Diffuse developmental disorder of the lung; Infant; NKX2.1; Pulmonary hypertension; Surfactant

Domains: Human genetics; Pulmonology and respiratory tract

Yohan Soreze, Nadia Nathan, Julien Jegard, Erik Hervieux, Pauline Clermidi, et al.. Acinar Dysplasia in a Full-Term Newborn with a NKX2.1 Variant. Neonatology, 2024, pp.1 - 4. ⟨10.1159/000534076⟩. ⟨inserm-04412777⟩