Deep phenotyping of the neuroimaging and skeletal features in KBG syndrome: a study of 53 patients and review of the literature.


Journal

Journal of medical genetics
ISSN: 1468-6244
Titre abrégé: J Med Genet
Pays: England
ID NLM: 2985087R

Informations de publication

Date de publication:
27 Nov 2023
Historique:
received: 03 01 2023
accepted: 30 06 2023
medline: 29 11 2023
pubmed: 17 8 2023
entrez: 16 8 2023
Statut: epublish

Résumé

KBG syndrome is caused by haploinsufficiency of CNS and/or skeletal imaging were collected from molecularly confirmed individuals with KBG syndrome through an international network. We evaluated the original imaging and compared our results with data in the literature. We identified 53 individuals, 44 with CNS and 40 with skeletal imaging. Common CNS findings included incomplete hippocampal inversion and posterior fossa malformations; these were significantly more common than previously reported (63.4% and 65.9% vs 1.1% and 24.7%, respectively). Additional features included patulous internal auditory canal, never described before in KBG syndrome, and the recurrence of ventriculomegaly, encephalic cysts, empty sella and low-lying conus medullaris. We found no correlation between these structural anomalies and epilepsy or intellectual disability. Prevalent skeletal findings comprised abnormalities of the spine including scoliosis, coccygeal anomalies and cervical ribs. Hand X-rays revealed frequent abnormalities of carpal bone morphology and maturation, including a greater delay in ossification compared with metacarpal/phalanx bones. This cohort enabled us to describe the prevalence of very heterogeneous neuroradiological and skeletal anomalies in KBG syndrome. Knowledge of the spectrum of such anomalies will aid diagnostic accuracy, improve patient care and provide a reference for future research on the effects of

Sections du résumé

BACKGROUND BACKGROUND
KBG syndrome is caused by haploinsufficiency of
METHODS METHODS
CNS and/or skeletal imaging were collected from molecularly confirmed individuals with KBG syndrome through an international network. We evaluated the original imaging and compared our results with data in the literature.
RESULTS RESULTS
We identified 53 individuals, 44 with CNS and 40 with skeletal imaging. Common CNS findings included incomplete hippocampal inversion and posterior fossa malformations; these were significantly more common than previously reported (63.4% and 65.9% vs 1.1% and 24.7%, respectively). Additional features included patulous internal auditory canal, never described before in KBG syndrome, and the recurrence of ventriculomegaly, encephalic cysts, empty sella and low-lying conus medullaris. We found no correlation between these structural anomalies and epilepsy or intellectual disability. Prevalent skeletal findings comprised abnormalities of the spine including scoliosis, coccygeal anomalies and cervical ribs. Hand X-rays revealed frequent abnormalities of carpal bone morphology and maturation, including a greater delay in ossification compared with metacarpal/phalanx bones.
CONCLUSION CONCLUSIONS
This cohort enabled us to describe the prevalence of very heterogeneous neuroradiological and skeletal anomalies in KBG syndrome. Knowledge of the spectrum of such anomalies will aid diagnostic accuracy, improve patient care and provide a reference for future research on the effects of

Identifiants

pubmed: 37586838
pii: jmg-2023-109141
doi: 10.1136/jmg-2023-109141
pmc: PMC10715526
doi:

Substances chimiques

Repressor Proteins 0
Transcription Factors 0

Types de publication

Review Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

1224-1234

Informations de copyright

© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Déclaration de conflit d'intérêts

Competing interests: None declared.

Références

Am J Hum Genet. 2011 Aug 12;89(2):289-94
pubmed: 21782149
Eur J Paediatr Neurol. 2021 Nov;35:8-15
pubmed: 34547584
Epilepsia. 2021 Feb;62(2):383-396
pubmed: 33325054
Biomed Res Int. 2016;2016:8034613
pubmed: 27975060
Arch Otolaryngol Head Neck Surg. 2003 Sep;129(9):992-3
pubmed: 12975274
Am J Med Genet. 1994 Sep 1;52(3):302-7
pubmed: 7810561
Eur J Hum Genet. 2010 Apr;18(4):429-35
pubmed: 19920853
Mol Syndromol. 2019 May;10(3):130-138
pubmed: 31191201
Genet Med. 2022 Oct;24(10):2051-2064
pubmed: 35833929
J Pers Med. 2022 Mar 05;12(3):
pubmed: 35330407
Growth Horm IGF Res. 2017 Dec;37:19-25
pubmed: 29107171
Am J Med Genet A. 2020 May;182(5):1073-1083
pubmed: 32124548
BMC Med Genet. 2019 Jan 14;20(1):16
pubmed: 30642272
Am J Med Genet A. 2017 Jul;173(7):1866-1877
pubmed: 28449295
Rofo. 2015 Jun;187(6):450-8
pubmed: 25905691
Am J Med Genet A. 2018 Sep;176(9):1991-1995
pubmed: 30088855
Biochem Biophys Res Commun. 2007 Jul 13;358(4):1034-40
pubmed: 17521611
Am J Med Genet A. 2007 Feb 1;143A(3):292-300
pubmed: 17230487
Orphanet J Rare Dis. 2006 Dec 12;1:50
pubmed: 17163996
Ann N Y Acad Sci. 2009 Jan;1151:38-67
pubmed: 19154516
Neurobiol Dis. 2018 Mar;111:138-152
pubmed: 29274743
Genet Med. 2020 Feb;22(2):245-257
pubmed: 31690835
Am J Med Genet A. 2004 Dec 1;131(2):150-4
pubmed: 15384099
Pediatr Int. 2021 Dec;63(12):1530-1532
pubmed: 34418234
Birth Defects Orig Artic Ser. 1975;11(5):7-18
pubmed: 1218237
Front Neuroanat. 2015 Dec 22;9:160
pubmed: 26733822
Rev Neurol (Paris). 2021 May;177(5):498-507
pubmed: 32826067
Genet Med. 2015 May;17(5):405-24
pubmed: 25741868
J Pediatr Orthop. 2022 May-Jun 01;42(5):e538-e543
pubmed: 35297389
Eur J Hum Genet. 2015 Sep;23(9):1176-85
pubmed: 25424714
J Hum Genet. 2017 Aug;62(8):741-746
pubmed: 28250421
Eur J Hum Genet. 2017 Jun;25(6):694-701
pubmed: 28422132
Physiol Genomics. 2008 Feb 19;32(3):311-21
pubmed: 17986521
Eur J Hum Genet. 2012 Feb;20(2):131-3
pubmed: 21654729
Am J Med Genet A. 2004 Oct 15;130A(3):284-7
pubmed: 15378538
Front Cell Dev Biol. 2021 Apr 29;9:645386
pubmed: 33996804
J Pediatr Orthop. 2016 Dec;36(8):e106-e110
pubmed: 26398433
Arch Gynecol Obstet. 2007 Nov;276(5):487-90
pubmed: 17453222
Ital J Pediatr. 2021 Jan 25;47(1):15
pubmed: 33494799
Neurocirugia (Astur : Engl Ed). 2022 Jul-Aug;33(4):157-164
pubmed: 35725217
Am J Med Genet A. 2004 Dec 1;131(2):144-9
pubmed: 15523620
Am J Med Genet A. 2016 Nov;170(11):2835-2846
pubmed: 27667800
Orphanet J Rare Dis. 2017 Dec 19;12(1):183
pubmed: 29258554
Surg Neurol Int. 2022 Jan 29;13:33
pubmed: 35242399

Auteurs

Francesca Peluso (F)

Medical Genetics Unit, Maternal and Child Health Department, Azienda USL-IRCCS di Reggio Emilia, Reggio Emilia, Emilia-Romagna, Italy.

Stefano G Caraffi (SG)

Medical Genetics Unit, Maternal and Child Health Department, Azienda USL-IRCCS di Reggio Emilia, Reggio Emilia, Emilia-Romagna, Italy.

Gianluca Contrò (G)

Medical Genetics Unit, Maternal and Child Health Department, Azienda USL-IRCCS di Reggio Emilia, Reggio Emilia, Emilia-Romagna, Italy.

Lara Valeri (L)

Medical Genetics Unit, Maternal and Child Health Department, Azienda USL-IRCCS di Reggio Emilia, Reggio Emilia, Emilia-Romagna, Italy.
Department of Pediatrics, University of Modena and Reggio Emilia Faculty of Medicine and Surgery, Modena, Emilia-Romagna, Italy.

Manuela Napoli (M)

Neuroradiology Unit, Azienda USL - IRCCS di Reggio Emilia, Reggio Emilia, Emilia-Romagna, Italy.

Giorgia Carboni (G)

Radiology Unit, Azienda USL - IRCCS di Reggio Emilia, Reggio Emilia, Emilia-Romagna, Italy.

Alka Seth (A)

Radiology, Rigshospitalet, Kobenhavn, Denmark.

Roberta Zuntini (R)

Medical Genetics Unit, Maternal and Child Health Department, Azienda USL-IRCCS di Reggio Emilia, Reggio Emilia, Emilia-Romagna, Italy.

Emanuele Coccia (E)

Medical Genetics Unit, Maternal and Child Health Department, Azienda USL-IRCCS di Reggio Emilia, Reggio Emilia, Emilia-Romagna, Italy.

Guja Astrea (G)

Department of Developmental Neuroscience, IRCCS Stella Maris Foundation, Calambrone, Toscana, Italy.

Anne-Marie Bisgaard (AM)

Center for Rare Diseases, Department of Pediatrics and Adolescent Medicine, Copenhagen University Hospital, Kobenhavn, Denmark.

Ivan Ivanovski (I)

Institute of Medical Genetics, University of Zurich, Zurich, Switzerland.

Silvia Maitz (S)

Service of Medical Genetics, IOSI, EOC, Lugano, Switzerland.

Elise Brischoux-Boucher (E)

Hunter Genetics, John Hunter Hospital, New Lambton Heights, New South Wales, Australia.

Melissa T Carter (MT)

The University of Newcastle, Callaghan, New South Wales, Australia.

Maria Lisa Dentici (ML)

Department of Clinical Genetics, Copenhagen University Hospital, Kobenhavn, Denmark.

Koenraad Devriendt (K)

Department for Epilepsy Genetics and Personalized Medicine, Danish Epilepsy Centre, Dianalund, Denmark.

Melissa Bellini (M)

Department of Pediatrics, University of Modena and Reggio Emilia, Modena, Italy.

Maria Cristina Digilio (MC)

Department of Medical and Surgical Sciences of the Mother, Children and Adults, University of Modena and Reggio Emilia, Modena, Italy.

Asif Doja (A)

The University of Newcastle, Callaghan, New South Wales, Australia.

David A Dyment (DA)

The University of Newcastle, Callaghan, New South Wales, Australia.

Stense Farholt (S)

Department of Human Genetics, Radboud University Medical Center, Nijmegen, Gelderland, Netherlands.

Carlos R Ferreira (CR)

Medical Genetics Unit, Centro Hospitalar e Universitário de Coimbra EPE, Coimbra, Coimbra, Portugal.

Lynne A Wolfe (LA)

Medical Genetics Unit, Centro Hospitalar e Universitário de Coimbra EPE, Coimbra, Coimbra, Portugal.

William A Gahl (WA)

National Human Genome Research Institute, Bethesda, Maryland, USA.

Maria Gnazzo (M)

Translational Cytogenomics Research Unit, Laboratory of Medical Genetics, Bambino Gesu Pediatric Hospital, Roma, Lazio, Italy.

Himanshu Goel (H)

Hunter Genetics, John Hunter Hospital, New Lambton Heights, New South Wales, Australia.
The University of Newcastle, Callaghan, New South Wales, Australia.

Sabine Weller Grønborg (SW)

Center for Rare Diseases, Department of Pediatrics and Adolescent Medicine, Copenhagen University Hospital, Kobenhavn, Denmark.
Department of Clinical Genetics, Copenhagen University Hospital, Kobenhavn, Denmark.

Trine Hammer (T)

Department of Clinical Genetics, Copenhagen University Hospital, Kobenhavn, Denmark.
Department for Epilepsy Genetics and Personalized Medicine, Danish Epilepsy Centre, Dianalund, Denmark.

Lorenzo Iughetti (L)

Department of Pediatrics, University of Modena and Reggio Emilia, Modena, Italy.
Department of Medical and Surgical Sciences of the Mother, Children and Adults, University of Modena and Reggio Emilia, Modena, Italy.

Tjitske Kleefstra (T)

Department of Human Genetics, Radboud University Medical Center, Nijmegen, Gelderland, Netherlands.

David A Koolen (DA)

Department of Human Genetics, Radboud University Medical Center, Nijmegen, Gelderland, Netherlands.

Francesca Romana Lepri (FR)

Translational Cytogenomics Research Unit, Laboratory of Medical Genetics, Bambino Gesu Pediatric Hospital, Roma, Lazio, Italy.

Gabrielle Lemire (G)

Department of Genetics, Children's Hospital of Eastern Ontario (CHEO), Ottawa, Ontario, Canada.

Pedro Louro (P)

Medical Genetics Unit, Centro Hospitalar e Universitário de Coimbra EPE, Coimbra, Coimbra, Portugal.

Gary McCullagh (G)

Royal Manchester Children's Hospital and University of Manchester, Royal Manchester Children's Hospital, Manchester, Manchester, UK.

Simona F Madeo (SF)

Department of Medical and Surgical Sciences of the Mother, Children and Adults, University of Modena and Reggio Emilia, Modena, Italy.

Annarita Milone (A)

Department of Developmental Neuroscience, IRCCS Stella Maris Foundation, Calambrone, Toscana, Italy.

Roberta Milone (R)

Department of Developmental Neuroscience, IRCCS Stella Maris Foundation, Calambrone, Toscana, Italy.

Jens Erik Klint Nielsen (JEK)

Department of Pediatrics, Zealand University Hospital Roskilde, Roskilde, Sjaelland, Denmark.

Antonio Novelli (A)

Translational Cytogenomics Research Unit, Laboratory of Medical Genetics, Bambino Gesu Pediatric Hospital, Roma, Lazio, Italy.

Charlotte W Ockeloen (CW)

Department of Human Genetics, Radboud University Medical Center, Nijmegen, Gelderland, Netherlands.

Rosario Pascarella (R)

Neuroradiology Unit, Azienda USL - IRCCS di Reggio Emilia, Reggio Emilia, Emilia-Romagna, Italy.

Tommaso Pippucci (T)

U.O. Genetica Medica, IRCCS Azienda Ospedaliero-Universitaria di Bologna Policlinico S Orsola, Bologna, Emilia-Romagna, Italy.

Ivana Ricca (I)

Department of Developmental Neuroscience, IRCCS Stella Maris Foundation, Calambrone, Toscana, Italy.

Stephen P Robertson (SP)

Department of Women's and Children's Health, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand.

Sarah Sawyer (S)

Department of Genetics, Children's Hospital of Eastern Ontario (CHEO), Ottawa, Ontario, Canada.

Marie Falkenberg Smeland (M)

Department of Medical Genetics, University Hospital of North Norway, Tromso, Troms, Norway.

Sander Stegmann (S)

Department of Clinical Genetics and School for Oncology and Developmental Biology, Maastricht University Medical Centre+, Maastricht, Limburg, Netherlands.

Constanze T Stumpel (CT)

Department of Clinical Genetics and School for Oncology and Developmental Biology, Maastricht University Medical Centre+, Maastricht, Limburg, Netherlands.

Amy Goel (A)

University of Newcastle, Callaghan, The University of Newcastle, Callaghan, New South Wales, Australia.

Juliet M Taylor (JM)

Genetic Health Service - Northern Hub, Genetic Health Service - Northern Hub, Aukland, New Zealand.

Domenico Barbuti (D)

Radiology and Bioimaging Unit, Bambino Gesu Pediatric Hospital, Roma, Lazio, Italy.

Annarosa Soresina (A)

Paediatrics Clinic and Institute for Molecular Medicine A. Nocivelli, Department of Clinical and Ex-perimental Sciences, ASST Spedali Civili di Brescia, Brescia, Lombardia, Italy.

Maria Francesca Bedeschi (MF)

Medical Genetic Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.

Roberta Battini (R)

Department of Developmental Neuroscience, IRCCS Stella Maris Foundation, Calambrone, Toscana, Italy.
Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Toscana, Italy.

Anna Cavalli (A)

Child Neurology and Psychiatry Unit, Azienda USL - IRCCS di Reggio Emilia, Reggio Emilia, Emilia-Romagna, Italy.

Carlo Fusco (C)

Child Neurology and Psychiatry Unit, Azienda USL - IRCCS di Reggio Emilia, Reggio Emilia, Emilia-Romagna, Italy.

Maria Iascone (M)

Laboratory of Medical Genetics, ASST Papa Giovanni XXIII, Bergamo, Lombardia, Italy.

Lionel Van Maldergem (L)

Centre de génétique humaine, Université de Franche-Comté, Centre Hospitalier Universitaire de Besancon, Besancon, France.

Sunita Venkateswaran (S)

The University of Newcastle, Callaghan, New South Wales, Australia.

Orsetta Zuffardi (O)

Department of Molecular Medicine, University of Pavia, Pavia, Lombardia, Italy.

Samantha Vergano (S)

Division of Medical Genetics and Metabolism, Children's Hospital of The King's Daughters, Norfolk, Virginia, USA.

Livia Garavelli (L)

Medical Genetics Unit, Maternal and Child Health Department, Azienda USL-IRCCS di Reggio Emilia, Reggio Emilia, Emilia-Romagna, Italy livia.garavelli@ausl.re.it.

Allan Bayat (A)

Department for Epilepsy Genetics and Personalized Medicine, Danish Epilepsy Centre, Dianalund, Denmark.
Institute for Regional Health Services Research, University of Southern Denmark, Odense, Syddanmark, Denmark.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female
Humans United States Aged Cross-Sectional Studies Medicare Part C
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH