ASXL1-related Bohring-Optiz Syndrome complicated by Persistent Neonatal Pulmonary Hypertension and Abnormal Alveoli Formation

Makoto Arioka; Shinji Nakamura; Katsufumi Nishioka; Kota Inoue; Yasuhiro Nakao; Yumi Miyai; Hirosuke Morita; Kosuke Koyano; Toshiki Takenouchi; Saneyuki Yasuda; Yoichi Chiba; Takashi Iwase; Masaki Ueno; Takashi Kusaka

doi:10.1016/j.ejmg.2024.104978

ASXL1-related Bohring-Optiz Syndrome complicated by Persistent Neonatal Pulmonary Hypertension and Abnormal Alveoli Formation

Eur J Med Genet. 2024 Oct 16:104978. doi: 10.1016/j.ejmg.2024.104978. Online ahead of print.

Authors

Makoto Arioka¹, Shinji Nakamura², Katsufumi Nishioka³, Kota Inoue⁴, Yasuhiro Nakao⁵, Yumi Miyai⁶, Hirosuke Morita⁷, Kosuke Koyano⁸, Toshiki Takenouchi⁹, Saneyuki Yasuda¹⁰, Yoichi Chiba¹¹, Takashi Iwase¹², Masaki Ueno¹³, Takashi Kusaka¹⁴

Affiliations

¹ Maternal and Perinatal Center, Kagawa University Hospital, Kagawa, Japan. Electronic address: [email protected].
² Department of Pediatrics, Faculty of Medicine, Kagawa University, Kagawa, Japan. Electronic address: [email protected].
³ Department of Pediatrics, Faculty of Medicine, Kagawa University, Kagawa, Japan. Electronic address: [email protected].
⁴ Department of Pediatrics, Faculty of Medicine, Kagawa University, Kagawa, Japan. Electronic address: [email protected].
⁵ Department of Pediatrics, Faculty of Medicine, Kagawa University, Kagawa, Japan. Electronic address: [email protected].
⁶ Department of Pathology and Host Defense, Faculty of Medicine, Kagawa University, Kagawa, Japan. Electronic address: [email protected].
⁷ Maternal and Perinatal Center, Kagawa University Hospital, Kagawa, Japan. Electronic address: [email protected].
⁸ Maternal and Perinatal Center, Kagawa University Hospital, Kagawa, Japan. Electronic address: [email protected].
⁹ Department of Pediatrics, School of Medicine, Keio University, Tokyo, Japan. Electronic address: [email protected].
¹⁰ Clinical training center, Kagawa University Hospital, Kagawa, Japan. Electronic address: [email protected].
¹¹ Department of Pathology and Host Defense, Faculty of Medicine, Kagawa University, Kagawa, Japan. Electronic address: [email protected].
¹² Department of Pediatrics, Faculty of Medicine, Kagawa University, Kagawa, Japan. Electronic address: [email protected].
¹³ Department of Pathology and Host Defense, Faculty of Medicine, Kagawa University, Kagawa, Japan. Electronic address: [email protected].
¹⁴ Department of Pediatrics, Faculty of Medicine, Kagawa University, Kagawa, Japan. Electronic address: [email protected].

PMID: 39423952
DOI: 10.1016/j.ejmg.2024.104978

Abstract

Bohring-Opitz syndrome (BOS) is a rare disease with a characteristic facial appearance and limb position. This report describes a case of BOS complicated by persistent pulmonary hypertension of the newborn (PPHN) and formation of abnormal alveoli that was confirmed by autopsy. A female neonate was born by cesarean section at 37 weeks and 2 days of gestation and found to have a nevus flammeus, exophthalmos, abnormal palate, retraction of the mandible, and a posture characteristic of BOS. The patients had severe PPHN requiring inhalation of nitric oxide. Genetic testing revealed a de novo frameshift variant in ASXL1. Autopsy revealed that the lung was at the saccular stage, equivalent to 28-34 weeks of gestation. This is the first report to present pathological evidence of immaturity of the lung that may be associated with PPHN in a patient with BOS caused by a variant in ASXL1.

Keywords: ASXL1; Bohring-Opitz syndrome; persistent pulmonary hypertension of the newborn; respiratory distress syndrome.

Publication types

Case Reports