Phenotypic expansion of the BPTF-related neurodevelopmental disorder with dysmorphic facies and distal limb anomalies

Kevin E. Glinton; Anna C.E. 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 Steensbjerre Møller; Irma van de Beek; Linda Zuurbier; Phillis Lakeman; Allan Bayat; Julian Martinez; Rebecca Signer; Pernille M. Torring; Morten Buch Engelund; Karen W. Gripp; Louise Amlie-Wolf; Lindsay B. Henderson; Alina T. Midro; Eugeniusz Tarasów; Beata Stasiewicz-Jarocka; Diana Moskal-Jasinska; Paul Vos; Felix Boschann; Corinna Stoltenburg; Oliver Puk; Inger Lise Mero; Kristine Lossius; Cyril Mignot; Boris Keren; Johanna C. Acosta Guio; Ignacio Briceño; Alberto Gomez; Yaping Yang; Pawel Stankiewicz

doi:10.1002/ajmg.a.62102

Phenotypic expansion of the BPTF-related neurodevelopmental disorder with dysmorphic facies and distal limb anomalies

Kevin E. Glinton, Anna C.E. 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 Steensbjerre MøllerIrma van de Beek, Linda Zuurbier, Phillis Lakeman, Allan Bayat, Julian Martinez, Rebecca Signer, Pernille M. Torring, Morten Buch Engelund, Karen W. Gripp, Louise Amlie-Wolf, Lindsay B. Henderson, Alina T. Midro, Eugeniusz Tarasów, Beata Stasiewicz-Jarocka, Diana Moskal-Jasinska, Paul Vos, Felix Boschann, Corinna Stoltenburg, Oliver Puk, Inger Lise Mero, Kristine Lossius, Cyril Mignot, Boris Keren, Johanna C. Acosta Guio, Ignacio Briceño, Alberto Gomez, Yaping Yang, Pawel Stankiewicz

Research output: Contribution to journal › Article › peer-review

10 Scopus citations

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.

Original language	English
Pages (from-to)	1366-1378
Number of pages	13
Journal	American Journal of Medical Genetics, Part A
Volume	185
Issue number	5
DOIs	https://doi.org/10.1002/ajmg.a.62102
State	Published - May 2021

Keywords

chromatin remodeling
epilepsy
microcephaly

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Glinton, K. E., Hurst, A. C. E., Bowling, K. M., Cristian, I., Haynes, D., Adstamongkonkul, D., Schnappauf, O., Beck, D. B., Brewer, C., Parikh, A. S., Shinde, D. N., Donaldson, A., Brautbar, A., Koene, S., van Haeringen, A., Piton, A., Capri, Y., Furlan, M., Gardella, E., ... Stankiewicz, P. (2021). Phenotypic expansion of the BPTF-related neurodevelopmental disorder with dysmorphic facies and distal limb anomalies. American Journal of Medical Genetics, Part A, 185(5), 1366-1378. https://doi.org/10.1002/ajmg.a.62102

@article{b42f13c1be2444d693328edc43431c14,

title = "Phenotypic expansion of the BPTF-related neurodevelopmental disorder with dysmorphic facies and distal limb anomalies",

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.",

keywords = "chromatin remodeling, epilepsy, microcephaly",

author = "Glinton, {Kevin E.} and Hurst, {Anna C.E.} and Bowling, {Kevin M.} and Ingrid Cristian and Devon Haynes and Dusit Adstamongkonkul and Oskar Schnappauf and Beck, {David B.} and Carole Brewer and Parikh, {Aditi Shah} and Shinde, {Deepali N.} and Alan Donaldson and Ariel Brautbar and Saskia Koene and {van Haeringen}, Arie and Am{\'e}lie Piton and Yline Capri and Margherita Furlan and Elena Gardella and M{\o}ller, {Rikke Steensbjerre} and {van de Beek}, Irma and Linda Zuurbier and Phillis Lakeman and Allan Bayat and Julian Martinez and Rebecca Signer and Torring, {Pernille M.} and Engelund, {Morten Buch} and Gripp, {Karen W.} and Louise Amlie-Wolf and Henderson, {Lindsay B.} and Midro, {Alina T.} and Eugeniusz Taras{\'o}w and Beata Stasiewicz-Jarocka and Diana Moskal-Jasinska and Paul Vos and Felix Boschann and Corinna Stoltenburg and Oliver Puk and Mero, {Inger Lise} and Kristine Lossius and Cyril Mignot and Boris Keren and {Acosta Guio}, {Johanna C.} and Ignacio Brice{\~n}o and Alberto Gomez and Yaping Yang and Pawel Stankiewicz",

note = "Publisher Copyright: {\textcopyright} 2021 The Authors. American Journal of Medical Genetics Part A published by Wiley Periodicals LLC.",

year = "2021",

month = may,

doi = "10.1002/ajmg.a.62102",

language = "English",

volume = "185",

pages = "1366--1378",

journal = "American Journal of Medical Genetics, Part A",

issn = "1552-4825",

number = "5",

}

Glinton, KE, Hurst, ACE, Bowling, KM, Cristian, I, Haynes, D, Adstamongkonkul, D, Schnappauf, O, Beck, DB, Brewer, C, Parikh, AS, Shinde, DN, Donaldson, A, Brautbar, A, Koene, S, van Haeringen, A, Piton, A, Capri, Y, Furlan, M, Gardella, E, Møller, RS, van de Beek, I, Zuurbier, L, Lakeman, P, Bayat, A, Martinez, J, Signer, R, Torring, PM, Engelund, MB, Gripp, KW, Amlie-Wolf, L, Henderson, LB, Midro, AT, Tarasów, E, Stasiewicz-Jarocka, B, Moskal-Jasinska, D, Vos, P, Boschann, F, Stoltenburg, C, Puk, O, Mero, IL, Lossius, K, Mignot, C, Keren, B, Acosta Guio, JC, Briceño, I, Gomez, A, Yang, Y & Stankiewicz, P 2021, 'Phenotypic expansion of the BPTF-related neurodevelopmental disorder with dysmorphic facies and distal limb anomalies', American Journal of Medical Genetics, Part A, vol. 185, no. 5, pp. 1366-1378. https://doi.org/10.1002/ajmg.a.62102

TY - JOUR

T1 - Phenotypic expansion of the BPTF-related neurodevelopmental disorder with dysmorphic facies and distal limb anomalies

AU - Glinton, Kevin E.

AU - Hurst, Anna C.E.

AU - Bowling, Kevin M.

AU - Cristian, Ingrid

AU - Haynes, Devon

AU - Adstamongkonkul, Dusit

AU - Schnappauf, Oskar

AU - Beck, David B.

AU - Brewer, Carole

AU - Parikh, Aditi Shah

AU - Shinde, Deepali N.

AU - Donaldson, Alan

AU - Brautbar, Ariel

AU - Koene, Saskia

AU - van Haeringen, Arie

AU - Piton, Amélie

AU - Capri, Yline

AU - Furlan, Margherita

AU - Gardella, Elena

AU - Møller, Rikke Steensbjerre

AU - van de Beek, Irma

AU - Zuurbier, Linda

AU - Lakeman, Phillis

AU - Bayat, Allan

AU - Martinez, Julian

AU - Signer, Rebecca

AU - Torring, Pernille M.

AU - Engelund, Morten Buch

AU - Gripp, Karen W.

AU - Amlie-Wolf, Louise

AU - Henderson, Lindsay B.

AU - Midro, Alina T.

AU - Tarasów, Eugeniusz

AU - Stasiewicz-Jarocka, Beata

AU - Moskal-Jasinska, Diana

AU - Vos, Paul

AU - Boschann, Felix

AU - Stoltenburg, Corinna

AU - Puk, Oliver

AU - Mero, Inger Lise

AU - Lossius, Kristine

AU - Mignot, Cyril

AU - Keren, Boris

AU - Acosta Guio, Johanna C.

AU - Briceño, Ignacio

AU - Gomez, Alberto

AU - Yang, Yaping

AU - Stankiewicz, Pawel

PY - 2021/5

Y1 - 2021/5

N2 - 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.

AB - 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.

KW - chromatin remodeling

KW - epilepsy

KW - microcephaly

UR - http://www.scopus.com/inward/record.url?scp=85100012342&partnerID=8YFLogxK

U2 - 10.1002/ajmg.a.62102

DO - 10.1002/ajmg.a.62102

M3 - Article

C2 - 33522091

AN - SCOPUS:85100012342

SN - 1552-4825

VL - 185

SP - 1366

EP - 1378

JO - American Journal of Medical Genetics, Part A

JF - American Journal of Medical Genetics, Part A

IS - 5

ER -

Phenotypic expansion of the BPTF-related neurodevelopmental disorder with dysmorphic facies and distal limb anomalies

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Keywords

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