Phenotypic expansion of the <scp><i>BPTF</i></scp>‐related neurodevelopmental disorder with dysmorphic facies and distal limb anomalies
Kevin E. Glinton, Anna Hurst, Kevin M. Bowling, Ingrid Cristian, Devon Haynes, Dusit Adstamongkonkul, Oskar Schnappauf, David B. Beck, Carole Brewer, Aditi Shah Parikh, Deepali N. Shinde, Alan Donaldson, Ariel Brautbar, Saskia Koene, Arie van Haeringen, Amélie Piton, Yline Capri, Margherita Furlan, Elena Gardella, Rikke S. Møller, Irma van de Beek, Linda Zuurbier, Phillis Lakeman, Allan Bayat, Julián A. Martínez-Agosto, Rebecca Signer, Pernille Mathiesen Tørring, Morten Buch Engelund, Karen W. Gripp, Louise Amlie‐Wolf, Lindsay B. Henderson, Alina T. Midro, Eugeniusz Tarasów, Beata Stasiewicz‐Jarocka, Diana Moskal-Jasińska, Paul de Vos, Felix Boschann, Corinna Stoltenburg, Oliver Puk, Inger‐Lise Mero, Kristine Lossius, Cyril Mignot, Boris Keren, Johanna Acosta, Ignacio Briceño, Alberto Gómez, Yaping Yang, Paweł Stankiewicz
Abstract
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.