RT Journal Article
SR Electronic
T1 Deep phenotyping of the neuroimaging and skeletal features in KBG syndrome: a study of 53 patients and review of the literature
JF Journal of Medical Genetics
JO J Med Genet
FD BMJ Publishing Group Ltd
SP 1224
OP 1234
DO 10.1136/jmg-2023-109141
VO 60
IS 12
A1 Peluso, Francesca
A1 Caraffi, Stefano G
A1 Contrò, Gianluca
A1 Valeri, Lara
A1 Napoli, Manuela
A1 Carboni, Giorgia
A1 Seth, Alka
A1 Zuntini, Roberta
A1 Coccia, Emanuele
A1 Astrea, Guja
A1 Bisgaard, Anne-Marie
A1 Ivanovski, Ivan
A1 Maitz, Silvia
A1 Brischoux-Boucher, Elise
A1 Carter, Melissa T
A1 Dentici, Maria Lisa
A1 Devriendt, Koenraad
A1 Bellini, Melissa
A1 Digilio, Maria Cristina
A1 Doja, Asif
A1 Dyment, David A
A1 Farholt, Stense
A1 Ferreira, Carlos R
A1 Wolfe, Lynne A
A1 Gahl, William A
A1 Gnazzo, Maria
A1 Goel, Himanshu
A1 Grønborg, Sabine Weller
A1 Hammer, Trine
A1 Iughetti, Lorenzo
A1 Kleefstra, Tjitske
A1 Koolen, David A
A1 Lepri, Francesca Romana
A1 Lemire, Gabrielle
A1 Louro, Pedro
A1 McCullagh, Gary
A1 Madeo, Simona F
A1 Milone, Annarita
A1 Milone, Roberta
A1 Nielsen, Jens Erik Klint
A1 Novelli, Antonio
A1 Ockeloen, Charlotte W.
A1 Pascarella, Rosario
A1 Pippucci, Tommaso
A1 Ricca, Ivana
A1 Robertson, Stephen P
A1 Sawyer, Sarah
A1 Falkenberg Smeland, Marie
A1 Stegmann, Sander
A1 Stumpel, Constanze T
A1 Goel, Amy
A1 Taylor, Juliet M
A1 Barbuti, Domenico
A1 Soresina, Annarosa
A1 Bedeschi, Maria Francesca
A1 Battini, Roberta
A1 Cavalli, Anna
A1 Fusco, Carlo
A1 Iascone, Maria
A1 Van Maldergem, Lionel
A1 Venkateswaran, Sunita
A1 Zuffardi, Orsetta
A1 Vergano, Samantha
A1 Garavelli, Livia
A1 Bayat, Allan
YR 2023
UL http://jmg.bmj.com/content/60/12/1224.abstract
AB Background KBG syndrome is caused by haploinsufficiency of ANKRD11 and is characterised by macrodontia of upper central incisors, distinctive facial features, short stature, skeletal anomalies, developmental delay, brain malformations and seizures. The central nervous system (CNS) and skeletal features remain poorly defined.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 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 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 ANKRD11 variants in skeletal and brain development.Data are available upon reasonable request. All data, except any confidential information about the study participants, are available on reasonable request by contacting the corresponding author. Novel variants have been submitted to the ClinVar database (accession numbers SCV003927975 to SCV003927993).