Hidenori Kawasaki, Kazuhiko Nakabayashi, Masahiko Ikeda, Tetsuo Onda, Seiichi Tomotaki, Masako Torishima, Akiko Saito, Hirofumi Ohashi, Sachiko Minamiguchi, Kenichiro Hata, Masahiro Hayakawa, Masahiko Kawai, Kazutoshi Cho, Shinji Kosugi, akahiro Yamada
Kyoto University School of Public Health, Kyoto University Hospital and Kyoto University. National Center for Child Health and Development. Hokkaido University Hospital. Nagoya University Hospital. Saitama Children’s Medical Center. Gunma University Graduate School of Medicine.
Japan
American Journal of Medical Genetics A
Am J Med Genet A 2025;
DOI: 10.1002/ajmg.a.64056
Abstract
Alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) is a lethal disease characterized by severe respiratory distress and pulmonary hypertension during the neonatal period, which is seldom diagnosed prenatally. Ten percent of ACDMPV cases are familial and caused by single nucleotide or copy-number variants in FOXF1 or the FOXF1 enhancer in an autosomal dominant manner. Here, we report a familial case of paternal FOXF1 upstream enhancer deletion, detected as somatic mosaicism in his blood specimen. A 37- and 35-year-old couple had four children. The first, third, and fourth children suffered from ACDMPV that led to neonatal death. In this case, the first child was misdiagnosed with meconium aspiration syndrome, and the diagnosis of ACDMPV was first made after the autopsy of the third child. The option of preimplantation or prenatal genetic testing did not exist during the pregnancy of the fourth child, as the complex genetic basis became clear only after the death of the fourth child.
Category
Class III. Pulmonary Hypertension Associated with Developmental Diseases of the Lung
Genetic Factors Associated with Pulmonary Vascular Disease
Age Focus: Pediatric Pulmonary Vascular Disease or Adult Pulmonary Vascular Disease
Fresh or Filed Publication: Fresh (PHresh). Less than 1-2 years since publication
Article Access
Free PDF File or Full Text Article Available Through PubMed or DOI: No