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

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.

Adolescent selfie: an Italian Society of Paediatrics survey of the lifestyle of teenagers.

BACKGROUND: Epidemiological studies worldwide indicate that teenagers are at risk of internalizing and externalizing problems that persist into adulthood. In our country, there are few epidemiological studies on adolescents internalizing and externalizing problems. These studies, however, were not conducted in all of Italy. The aim of this study, promoted by the Italian Society of Paediatrician (SIP), was to investigate: a) the lifestyle and the prevalence of internalizing and externalizing problems in Italian teenagers and b) the risk and protective factors in family and social contexts. A further aim was to analyse gender differences in the above-mentioned variables. METHODS: 11,527 adolescents aged 13 to 21 years were recruited among students of Italian high schools. Participants were contacted by school authorities inviting them to participate in an internet survey on youth health and lifestyle. If they agreed to participate, the adolescents filled out an on-line anonymous questionnaire. The questionnaire was composed of 60 multiple choice items to investigate nutrition, body perception and lifestyle, internet exposure and sexual behaviour, externalizing and internalizing problems, family context and social context. Participation in the study was completely voluntary. The statistical significance of gender differences was tested by means of Chi-square analyses. Results displayed that Italian female adolescents are at risk of internalizing problems while males are at higher risk of externalizing problems. Moreover, several risk factors emerged from the family context in terms of violence, physical and psychological abuse. CONCLUSIONS: It is critical to make paediatricians and schools aware of the main points to improve prevention and healthcare in the teenage population. To our knowledge, this is the first study in the Italian context to enrol more than 11,000 adolescents.

Massive asymptomatic creatine kinase elevation in youth during antipsychotic drug treatment: case reports and critical review of the literature.

A massive asymptomatic creatine kinase elevation (MACKE) has been described during antipsychotic exposure in adult psychotic patients without signs of neuroleptic malignant syndrome (NMS), or other most frequent reasons for high creatine kinase (CK) serum level (intramuscular injections, restraints, intense physical activity, dystonic reactions). In this article, we review this clinical condition, and report three cases of MACKE in nonpsychotic, drug-naïve youth during treatment with second generation antipsychotics. The diagnosis of MACKE should be considered after ruling out other possible common reasons of CK increase. The finding of MACKE should indicate a need for weekly monitoring of the CK level only when there are reasons to believe elevated CK is toxic or harmful. Further investigations are recommended when signs and symptoms raise a suspicion of NMS or rhabdomyolysis, including flu-like syndrome, fever, weakness, alteration of consciousness, muscle rigidity, tachycardia, hyper-/hypotension, and dark urine. A drug discontinuation should be considered when possible signs of NMS or rhabdomyolysis are suspected, or in cases of very high and persisting CK levels. Empirical evidence indicates that there is not a "safe" antipsychotic medication; therefore, a switch to another antipsychotic with a different profile is not necessarily a safe option. The spontaneously remitting or intermittent course suggests that the "true" MACKE should be kept distinct from both rhabdomyolysis and NMS. Raising awareness with MACKE may reduce the need for unnecessary diagnosis of NMS or rhabdomyolysis, which may otherwise lead to an unnecessary discontinuation of an effective therapeutic agent.

The Italian preadolescent mental health project (PrISMA): rationale and methods.

The Italian preadolescent mental health project (PrISMA--Progetto Italiano Salute Mentale Adolescenti) is the first Italian study designed to estimate the prevalence of mental disorders in preadolescents (10-14 years old) living in urban areas, and to analyse the demographic and biological correlates of emotional and behavioural problems. This paper describes the rationale, methods and the analysis plan of the project. The design of the study used a two-stage sampling procedure, one screening stage of emotional and behavioural problems in a large sample of subjects attending public and private schools and a second stage of diagnostic assessment in a sample including all high scorers and a proportion of low scorers. In the screening stage, parents of preadolescents were asked to fill in the Child Behavior Checklist (CBCL), whereas in the second stage preadolescents and their parents were administered the Development and Well Being Assessment for the assessment of mental disorders together with the Strengths and Difficulties Questionnaire and two scales (C-GAS and HoNOSCA) designed to evaluate the functioning of the preadolescent in different areas. Genetic samples were collected during the screening stage, after parents gave their informed written consent. The findings of this study are expected to allow an adequate planning of interventions for the prevention and the treatment of mental disorders in preadolescence as well as efficient health services.