PT  - JOURNAL ARTICLE
AU  - Peluso, Francesca
AU  - Caraffi, Stefano G
AU  - Contrò, Gianluca
AU  - Valeri, Lara
AU  - Napoli, Manuela
AU  - Carboni, Giorgia
AU  - Seth, Alka
AU  - Zuntini, Roberta
AU  - Coccia, Emanuele
AU  - Astrea, Guja
AU  - Bisgaard, Anne-Marie
AU  - Ivanovski, Ivan
AU  - Maitz, Silvia
AU  - Brischoux-Boucher, Elise
AU  - Carter, Melissa T
AU  - Dentici, Maria Lisa
AU  - Devriendt, Koenraad
AU  - Bellini, Melissa
AU  - Digilio, Maria Cristina
AU  - Doja, Asif
AU  - Dyment, David A
AU  - Farholt, Stense
AU  - Ferreira, Carlos R
AU  - Wolfe, Lynne A
AU  - Gahl, William A
AU  - Gnazzo, Maria
AU  - Goel, Himanshu
AU  - Grønborg, Sabine Weller
AU  - Hammer, Trine
AU  - Iughetti, Lorenzo
AU  - Kleefstra, Tjitske
AU  - Koolen, David A
AU  - Lepri, Francesca Romana
AU  - Lemire, Gabrielle
AU  - Louro, Pedro
AU  - McCullagh, Gary
AU  - Madeo, Simona F
AU  - Milone, Annarita
AU  - Milone, Roberta
AU  - Nielsen, Jens Erik Klint
AU  - Novelli, Antonio
AU  - Ockeloen, Charlotte W.
AU  - Pascarella, Rosario
AU  - Pippucci, Tommaso
AU  - Ricca, Ivana
AU  - Robertson, Stephen P
AU  - Sawyer, Sarah
AU  - Falkenberg Smeland, Marie
AU  - Stegmann, Sander
AU  - Stumpel, Constanze T
AU  - Goel, Amy
AU  - Taylor, Juliet M
AU  - Barbuti, Domenico
AU  - Soresina, Annarosa
AU  - Bedeschi, Maria Francesca
AU  - Battini, Roberta
AU  - Cavalli, Anna
AU  - Fusco, Carlo
AU  - Iascone, Maria
AU  - Van Maldergem, Lionel
AU  - Venkateswaran, Sunita
AU  - Zuffardi, Orsetta
AU  - Vergano, Samantha
AU  - Garavelli, Livia
AU  - Bayat, Allan
TI  - Deep phenotyping of the neuroimaging and skeletal features in KBG syndrome: a study of 53 patients and review of the literature
AID  - 10.1136/jmg-2023-109141
DP  - 2023 Dec 01
TA  - Journal of Medical Genetics
PG  - 1224--1234
VI  - 60
IP  - 12
4099  - http://jmg.bmj.com/content/60/12/1224.short
4100  - http://jmg.bmj.com/content/60/12/1224.full
SO  - J Med Genet2023 Dec 01; 60
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).