Department of Obstetrics and Gynecology, The Prenatal Diagnosis and Medical Genetics Program, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada.
Department of Genetics, CHEO, University of Ottawa, Ottawa, Ontario, Canada.
Am J Med Genet A. 2019 Jul;179(7):1325-1329. doi: 10.1002/ajmg.a.61162. Epub 2019 May 9.
Alveolar capillary dysplasia with misalignment of the pulmonary veins (ACDMPV) is a rare, autosomal dominant disorder of interstitial lung development, leading to pulmonary hypertension, and death in infancy. Associated features include malformations of the heart, gastrointestinal tract, and genitourinary system. ACDMPV is caused by heterozygous variants in the FOXF1 gene or microdeletions involving FOXF1. We present a male infant with ACDMPV, hypoplastic left heart sequence (HLHS), duodenal atresia, and imperforate anus due to a de novo, in frame deletion in FOXF1: c.209_214del (p.Thr70_Leu71del). Previous reports have suggested that microdeletions involving FOXF1 are associated with ACDMPV with congenital heart defects, including HLHS, gastrointestinal atresias, and other anomalies; whereas likely pathogenic variants within FOXF1 have not been reported with ACDMPV and HLHS. This is the first patient reported with ACDMPV, HLHS, imperforate anus, and duodenal atresia associated with a likely pathogenic variant in the FOXF1 gene.
肺泡毛细血管发育不良伴肺静脉异位（ACDMPV）是一种罕见的常染色体显性肺间质发育障碍疾病，可导致肺动脉高压和婴儿期死亡。相关特征包括心脏、胃肠道和泌尿生殖系统畸形。ACDMPV 是由 FOXF1 基因的杂合变异或涉及 FOXF1 的微缺失引起的。我们介绍了一名男性婴儿，患有 ACDMPV、左心发育不全序列（HLHS）、十二指肠闭锁和肛门闭锁，这是由于 FOXF1 中的从头、框内缺失引起的：c.209_214del（p.Thr70_Leu71del）。以前的报告表明，涉及 FOXF1 的微缺失与先天性心脏缺陷相关的 ACDMPV 相关，包括 HLHS、胃肠道闭锁和其他异常；而 FOXF1 内的可能致病性变异尚未与 ACDMPV 和 HLHS 相关报道。这是首例报道的与 FOXF1 中可能致病变异相关的 ACDMPV、HLHS、肛门闭锁和十二指肠闭锁患者。
