Obsessive Compulsive Symptoms and Psychopathological Profile in Children and Adolescents with KBG Syndrome

Alfieri, Paolo; Demaria, Francesco; Licchelli, Serena; Santonastaso, Ornella; Caciolo, Cristina; Digilio, María Cristina; Sinibaldi, Lorenzo; Leoni, Chiara; Gnazzo, Maria; Tartaglia, Marco; Pasqualetti, Patrizio; Vicari, Stefano

doi:10.3390/brainsci9110313

Cited by 8 publications

(12 citation statements)

References 48 publications

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“…It seems warranted to conduct in the future quantitative studies, with rating scales, as part of a longitudinal natural history study, as a way to really elaborate what ASD symptoms manifest in KBG syndrome, independent of the intellectual disability. However, from an overall psychiatric perspective, eighty percent had behavioral abnormalities, including aggressive and violent behavior, impulsivity, or repetitive compulsive behavior, consistent with what has been previously reported [33].…”

Section: Discussionsupporting

confidence: 84%

KBG Syndrome: Prospective Videoconferencing and Use of AI-driven Facial Phenotyping in 25 New Patients

Guo

Park

et al. 2021

Preprint

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Genetic variants in the gene Ankyrin Repeat Domain 11 (ANKRD11) and deletions in 16q24.3 are known to cause KBG syndrome, a rare syndrome associated with craniofacial, intellectual, and neurobehavioral anomalies. We report 25 unpublished individuals from 22 families, all with molecularly confirmed diagnoses of KBG syndrome. Twenty-one individuals have de novo variants, three have inherited variants, and one is inherited from a parent exhibiting low-level mosaicism. Of these variants, 20 are truncating (frameshift or nonsense), and five are missense. We created a novel protocol for collection and reporting of data, including prospectively interviewing these individuals and their families throughout eight countries via videoconferencing by a single clinician. Participants’ medical records, including imaging, were reviewed, and data was uploaded to the Human Disease Gene website using Human Phenotype Ontology (HPO) terms. Photos of the participants were submitted to GestaltMatcher and Face2Gene (FDNA Inc, USA) for facial analysis, and we found similar facial phenotypes among the participants. Within our cohort, common traits included short stature, macrodontia, anteverted nares, wide nasal bridge, wide nasal base, thick eyebrows, synophrys and hypertelorism. Seventy-two percent of participants had gastrointestinal complaints and 80% had hearing loss. Three participants were started on growth hormone with positive results. Behavioral issues and global developmental delays were found in most participants. Neurologic abnormalities including seizures and/or EEG abnormalities were also very common (44%), suggesting that early detection and seizure prophylaxis could be an important point of intervention. Twenty-four percent were diagnosed with attention deficit hyperactivity disorder (ADHD) and 28% were diagnosed with autism spectrum disorder (ASD). Additionally, we have identified minimally reported symptoms, including recurrent sinus infections (16%) and previously unreported migraines (20%). Based on the videoconferencing and these data, we provide a set of recommendations regarding diagnostic and treatment approaches for KBG syndrome.

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Section: Discussionsupporting

confidence: 84%

KBG Syndrome: Prospective Videoconferencing and Use of AI-driven Facial Phenotyping in 25 New Patients

Guo

Park

et al. 2021

Preprint

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“…Participants were recruited at the Child and Adolescent Psychiatry Units of Bambino Gesù Hospital and Policlinico Universitario Agostino Gemelli in Rome. Fifteen participants had already enrolled in a previous related study [ 25 ].…”

Section: Methodsmentioning

confidence: 99%

Cognitive and Adaptive Characterization of Children and Adolescents with KBG Syndrome: An Explorative Study

Alfieri

Caciolo

Lazzaro

et al. 2021

JCM

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KBG syndrome (KBGS) is a rare Mendelian condition caused by heterozygous mutations in ANKRD11 or microdeletions in chromosome 16q24.3 encompassing the gene. KBGS is clinically variable, which makes its diagnosis difficult in a significant proportion of cases. The present study aims at delineating the cognitive profile and adaptive functioning of children and adolescents with KBGS. Twenty-four Italian KBGS with a confirmed diagnosis by molecular testing of the causative ANKRD11 gene were recruited to define both cognitive profile as measured by the Wechsler Intelligence Scale and adaptive functioning as measured by Vineland Adaptive Behavior Scales-II Edition or the Adaptive Behavior Assessment System-II Edition. Among children and adolescents, 17 showed intellectual disability, six presented borderline intellectual functioning and only one child did not show cognitive defects. Concerning cognitive profile, results revealed significant differences between the four indexes of Wechsler Intelligence Scale. Namely, the verbal comprehension index was significantly higher than the perceptual reasoning index, working memory index and the processing speed index. Concerning adaptive functioning, no difference between the domains was found. In conclusion, in our cohort, a heterogeneous profile has been documented in cognitive profiles, with a spike on verbal comprehension, while a flat-trend has emerged in adaptive functioning. Our cognitive and adaptive characterization drives professionals to set the best clinical supports, capturing the complexity and heterogeneity of this rare condition.

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“…Haploinsufficiency of ANKRD11 due to microdeletion of chromosome 16q24.3 or loss of function mutation in the ANKRD11 gene results in the KBG syndrome phenotype, which includes neurodevelopmental problems. Alfieri et al reported a low mean TIQ score (66.0 ± 16.2, represented as mean ± SD) in 17 patients with KBG syndrome ( Alfieri et al, 2019 ), and van Dongen et al (2017) showed similar mean TIQ distribution (66.5 ± 15.6 in 12 children, 62.5 ± 7.1 in 6 adults). As mentioned above, most patients have moderate to mild ID and more than half of the adults with KBG syndrome have jobs and are self-sufficient in ordinary life ( Goldenberg et al, 2016 ; Low et al, 2016 ).…”

Section: Resultsmentioning

confidence: 98%

“…In addition to ID, some behavioral and psychopathologic problems such as ADHD, autism-like features, and impulsivity are major issues in patients with KBG syndrome ( Novara et al, 2017 ). In recent study of 17 pediatric patients with KBG syndrome, there was a higher prevalence of obsessive-compulsive traits, tic disorders, depressive mood, and ADHD as compared with the general population; obsessive-compulsive traits, in particular, did not seem to be related to cognitive level ( Alfieri et al, 2019 ). Similarly, another study also mentioned that ADHD-like behavioral problems associated with KBG syndrome could not be directly related or explained with a specific intelligence profile ( van Dongen et al, 2017 ).…”

Section: Resultsmentioning

confidence: 99%

Two Novel Mutations of ANKRD11 Gene and Wide Clinical Spectrum in KBG Syndrome: Case Reports and Literature Review

et al. 2020

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Background KBG syndrome (OMIM #148050) is a rare, autosomal dominant inherited genetic disorder caused by heterozygous mutations in the ankyrin repeat domain-containing protein 11 (ANKRD11) gene or by microdeletion of chromosome 16q24.3. It is characterized by macrodontia of the upper central incisors, distinctive facial dysmorphism, short stature, vertebral abnormalities, hand anomaly including clinodactyly, and various degrees of developmental delay. KBG syndrome presents with variable clinical feature and severity among individuals. Here, we report two KBG patients who have different novel heterozygous mutations of ANKRD11 gene with wide range of clinical manifestations. Case presentation Two novel heterozygous mutations of ANKRD11 gene were identified in two unrelated Korean patients with variable clinical presentations. The first patient presented with short stature and early puberty and was treated with growth hormone and gonadotropin-releasing hormone agonist without adverse effects. He had mild intellectual disability. In targeted exome sequencing, a novel de novo frameshift variant was identified in ANKRD11, c.5889del, and p. (Ile1963MetfsX9). The second patient had severe intellectual disability with epilepsy. He had normal height and prepubertal stage at the age of 11 years. He had behavioral problems such as autism-like features, anxiety, and stereotypical movements. Whole exome sequencing (WES) was performed, and the novel heterozygous mutation, c3310dup, p. (Glu110GlyfsTer5) in ANKRD11 was identified. Conclusion KBG syndrome is often underdiagnosed because of its non-specific features and phenotypic variability. Performing a next—generation sequencing panel, including the ANKRD11 gene for cases of developmental delay with/without short stature may be helpful to identify hitherto undiagnosed KBG syndrome patients.

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Obsessive Compulsive Symptoms and Psychopathological Profile in Children and Adolescents with KBG Syndrome

Cited by 8 publications

References 48 publications

KBG Syndrome: Prospective Videoconferencing and Use of AI-driven Facial Phenotyping in 25 New Patients

KBG Syndrome: Prospective Videoconferencing and Use of AI-driven Facial Phenotyping in 25 New Patients

Cognitive and Adaptive Characterization of Children and Adolescents with KBG Syndrome: An Explorative Study

Two Novel Mutations of ANKRD11 Gene and Wide Clinical Spectrum in KBG Syndrome: Case Reports and Literature Review

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