Department of Molecular & Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, Texas, USA.
Department of Genetics, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Am J Med Genet A. 2021 May;185(5):1366-1378. doi: 10.1002/ajmg.a.62102. Epub 2021 Jan 31.
Neurodevelopmental disorder with dysmorphic facies and distal limb anomalies (NEDDFL), defined primarily by developmental delay/intellectual disability, speech delay, postnatal microcephaly, and dysmorphic features, is a syndrome resulting from heterozygous variants in the dosage-sensitive bromodomain PHD finger chromatin remodeler transcription factor BPTF gene. To date, only 11 individuals with NEDDFL due to de novo BPTF variants have been described. To expand the NEDDFL phenotypic spectrum, we describe the clinical features in 25 novel individuals with 20 distinct, clinically relevant variants in BPTF, including four individuals with inherited changes in BPTF. In addition to the previously described features, individuals in this cohort exhibited mild brain abnormalities, seizures, scoliosis, and a variety of ophthalmologic complications. These results further support the broad and multi-faceted complications due to haploinsufficiency of BPTF.
神经发育障碍伴面畸形和远端肢体异常（NEDDFL），主要表现为发育迟缓/智力残疾、言语发育迟缓、出生后小头畸形和面畸形，是由 BPTF 基因（一种具有剂量敏感性的溴结构域 PHD 手指染色质重塑因子转录因子）杂合变异引起的综合征。迄今为止，仅有 11 名因 BPTF 新生变异导致 NEDDFL 的患者被描述过。为了扩大 NEDDFL 的表型谱，我们描述了 25 名新患者的临床特征，他们携带 20 种不同的、有临床意义的 BPTF 变异，包括 4 名携带 BPTF 遗传改变的患者。除了先前描述的特征外，该队列中的患者还表现出轻度脑异常、癫痫发作、脊柱侧凸和各种眼科并发症。这些结果进一步支持了 BPTF 单倍不足引起的广泛而多方面的并发症。
