Copy number variants analysis in a cohort of isolated and syndromic developmental delay/intellectual disability reveals novel genomic disorders, position effects and candidate disease genes.

BACKGROUND: Array-comparative genomic hybridization (array-CGH) is a widely used technique to detect copy number variants (CNVs) associated with developmental delay/intellectual disability (DD/ID). AIMS: Identification of genomic disorders in DD/ID. MATERIALS AND METHODS: We performed a comprehensive array-CGH investigation of 1,015 consecutive cases with DD/ID and combined literature mining, genetic evidence, evolutionary constraint scores, and functional information in order to assess the pathogenicity of the CNVs. RESULTS: We identified non-benign CNVs in 29% of patients. Amongst the pathogenic variants (11%), detected with a yield consistent with the literature, we found rare genomic disorders and CNVs spanning known disease genes. We further identified and discussed 51 cases with likely pathogenic CNVs spanning novel candidate genes, including genes encoding synaptic components and/or proteins involved in corticogenesis. Additionally, we identified two deletions spanning potential Topological Associated Domain (TAD) boundaries probably affecting the regulatory landscape. DISCUSSION AND CONCLUSION: We show how phenotypic and genetic analyses of array-CGH data allow unraveling complex cases, identifying rare disease genes, and revealing unexpected position effects.

Clinical, psychological and personality features related to age of onset of anorexia nervosa.

BACKGROUND: To investigate the relationship between age of onset and clinical and personality features of patients with anorexia nervosa (AN). SAMPLING AND METHOD: We assessed 250 outpatients with AN with the Temperament and Character Inventory, the Eating Disorder Inventory 2, the Beck Depression Inventory and the Body Shape Questionnaire. The patients were subdivided into 3 groups: early (n=73), intermediate (n=96) and late onset (n=81), based on age of onset of symptoms. RESULTS: The early-onset group shows higher body dissatisfaction, maturity fear, impulsivity and asceticism than the other 2 groups. This group shows a greater character fragility, as described in particular by a lower self-directedness, than the other 2 groups. CONCLUSIONS: Even several years after the onset of the disorder, early-onset subjects affected by AN seem characterized by a more disturbed personality, with a higher body dissatisfaction than late-onset subjects affected by AN and a pursuit of thinness based on an ascetic drive.

[Preadolescence and suicide attempts]. / Preadolescenza e tentativi di suicidio.

The authors refer their experience regarding suicide attempts in preadolescence, an age less discussed than adolescence in the international literature on the subject. A case-study of 27 patients (12 boys and 15 girls), all under 13 years and in-patients in the Child Neuropsychiatry Section of the Department of Pediatric and Adolescence Sciences of the Turin University during ten years (1990-1999), is described. Various criteria are taken into consideration, including incidence peaks, social extraction, birth order, methods used, psychiatric illness in the family, family break-ups, organic illness in the family, experience of loss, previous signs of emotional disturbance, precipitant events, any repeat attempts and the patients' psychopathological profiles, and the most important aspects are illustrated. The data resulting from the case-study show that suicide attempts by pre-teenagers are not as rare as commonly believed, especially at the age just before entering into true adolescence. The authors conclude by emphasising that suicide attempts seem to be a phenomenon involving particularly less well-off classes (a good 87% of the case-study); among the methods used, the ingestion of drugs is the most common, the incidence of psychiatric illness in the family (45%) is certainly relevant and in 70% of cases there were previous and evident signs of emotional disturbance. In consideration of the information already available and the findings reported in this study, attempted suicide attempts appear to be a <> and not a pathology, at which basis different psychopathological profiles can be found: it is a symptom of a serious emotional and relational problem, which rarely reveals itself suddenly and even more rarely is resolved without help.

Neurophysiologic exploration: a reliable tool in HIV-1 encephalopathy diagnosis in children.

BACKGROUND: HIV-1 related encephalopathy has a bad prognostic meaning in the course of AIDS disease, but the early association of different drugs can modify its course. For this reason it is very important to recognize CNS involvement as soon as possible. As shown in the literature, at least in adult studies, EEG and Evoked Potentials (EP) are good tools in evaluating CNS alterations. In children data are rare. METHODS: A ten-year prospective study of 44 infected children out of 142 born from HIV-1 positive mothers has been done. The children have been submitted to EEG recording every six months in the first 18 months of life and then every year, to multimodal EP every six months. A total of 357 EEG, 47 P-VEP, 62 F-VEP and 98 BAEP have been performed. RESULTS: EEG: we found no pathologic results in patients belonging to category A; results were pathologic in 17.7% in category B, in 47.7% in C and in 77% of encephalopathic patients. It seems that EEG alterations are parallel to disease progression, with a relative risk of developing encephalopathy (R.R. = 1.15) and of death (R.R. = 2.33) for patients belonging to category C. We obtained a statistically significant lengthening in BAEP interpeak latency of left ear in all groups. For patients in category C the risk of developing encephalopathy is statistically significant (p = 0.045; R.R. = 6.75) and risk of death is high (R.R. = 4). CONCLUSIONS: Neurophysiologic exams are a reliable tool for the diagnosis of encephalopathy, in addition to clinical evidence.

[Psychological assistance in organ transplantation]. / L'assistenza psicologica nei trapianti d'organo.

The aim of this report is introducing with a series of psychological, psychiatric and psychosocial problems, that can arise, at every point, in the procedure of organ transplantations. Different areas of intervention are considered: the assistance to the patients and their families during the pre- and post-operative periods; the evaluation of transplant recipients' quality of life; ethical and psychological problems of living kidney donation; psychosocial support to donors' families; the training of the intensive therapy units to entertain relationships with donors' relatives; the delicate psychological aspects of transplantation during childhood. The sense of awareness about these matters is growing in Italy too, and many initiatives of psychological and psychiatric help are being developed in collaboration with several transplantation centres.

Evolution of HIV-1 encephalopathy in children.

BACKGROUND: This study has been conducted on a series of HIV-1 infected children, with the aim of illustrating the features of encephalopathy onset, its evolution and its influence on life expectancy. The most useful exams for diagnosis are also outlined. METHODS: The perspective study lasted from January 1989 to June 1997. Forty six symptomatic patients, out of 142 seropositive children, were followed up in the Department of Paediatric and Adolescence Sciences of the University of Turin. The patients, now between 1 yr 2 mth and 13 yr 9 mth old, were born from HIV-1 seropositive mothers; seroreverters have been excluded. Scheduled neuropsychiatric consultations were used, consisting of a neurologic exam and an interview with parents, cognitive evaluations, EEGs, Evoked Potentials and CT scans. The results have been evaluated with log-rank test for the analysis of the survival curves. RESULTS: We found a significantly higher mortality rate in encephalopathic versus non encephalopathic patients; encephalopathic patients, in whom neurologic signs began in the first year of life, have a worse prognosis than the other patients, in whom encephalopathy appeared later. We did not find a statistical correlation between clinical course and immunological deficit. The clinical features of encephalopathy are mainly characterized by pyramidal signs and cognitive deterioration. Clinical sign evolution is linked to the age of encephalopathy onset: plateau pattern encephalopathy, characterized by an early onset, severe motor signs and cognitive delay from the very beginning, shows a greater severity and a shorter survival than progressive encephalopathy, characterized by a slowly progressive evolution of pyramidal signs, to which a cognitive deterioration may be added. CONCLUSIONS: Neuropsychological exams can be helpful in the diagnosis and follow-up of encephalopathy.

Diagnostic value of multimodal evoked potentials in HIV-1 infected children.

Evoked potentials (EP) help guide the diagnosis of central nervous system involvement in demyelinating pathologies regarding both children and adults, and in human immunodeficiency virus-1 (HIV-1) correlated pathologies only in regard to adult patients. EP have been shown to be useful in highlighting early signs of the disease. We therefore studied EP in HIV-1 infected children with the aim of verifying the association of results with disease progression, clinical signs and electroencephalogram, and individualizing the most reliable test. Thirty-six patients (20 male and 16 female subjects, age range: 10 months to 12 years) belonging to a group of 45 symptomatic subjects seen at the Pediatric Department were included into the study from November 1991 to December 1994. Ten presented with neurological signs as of disease onset, eight others developed encephalopathy during the follow-up. One hundred seventeen EP, i.e., 27 pattern visual, 64 flash visual and 26 brain stem auditory EP, were recorded. Univariate statistical analysis using the Wilcoxon-Mann-Whitney U test and Student's t test was done. As a whole, we found 22.5% of abnormal EP in subjects without neurological signs and 28.3% in subjects with neurological signs. Results that were obtained suggested a close relationship between both the pattern of visual and brain stem auditory EP exams and disease progression.

[Adolescence in patients with cystic fibrosis studied by Rorschach test]. / L'adolescenza nei pazienti con fibrosi cistica studiata col test di Rorschach.

BACKGROUND: The majority of patients with cystic fibrosis today reach adulthood. During adolescence, however, many ask themselves questions regarding their possible future realisation. AIMS: The aim of this study, which was performed using the Rorschach test, was to identify areas of particular problems in a group of CF adolescents monitored by the Pneumology Division of Regina Margherita Children's Hospital in Turin: 26 subjects aged between 14 and 18, including 11 females and 15 males. METHODS: The analysis of the test was based on the use of thought, interior resources, instincts and interpersonal relations. The type of intimate resonance was also taken into account and, lastly, a study of the contents was performed using a self-representation grid. RESULTS: The results obtained show a dishomogeneous profile of the development and quality of intellectual processes faced with the intensity of anxiety, mainly loss anxiety, linked to the disease, even if unrelated to its severity. The integration of emotive and instinctual aspects is difficult: mental development towards adult life appears to be impeded by the predominance of regressive modalities. CONCLUSIONS: On the basis of the study performed, it is possible to hypothesise the need for psychological help aimed at achieving a more evolved psychic organisation, possible as part of an overall management programme by the medical and nursing team.

[Personality structure in children with cystic fibrosis studied using Rorschach test]. / La strutturazione della personalità nei bambini con fibrosi cistica studiata col test di Rorschach.

BACKGROUND AND AIMS: The recent positive evolution in the development of cystic fibrosis, resulting in the current prospect of survival, has led to the formation of a new population of chronic patients. The characteristics of the disease and treatment (hereditary, early onset, affecting the alimentary tract and airways) may interfere with personality structuring processes. The aim of the study was to identify the psychopathological risk. METHODS: The study was performed using the Rorschach test in a population of children with cystic fibrosis monitored by the Pneumology Division of the Ospedale Infantile Regina Margherita in Turin: 20 children aged between 7 and 13 years old were included in the study, most of whom had been diagnosed before the age of 2. The analysis of tests was focused on the use of thought, interior resources, instincts and interpersonal relations. A study of the contents was also made using a self-representational grid. RESULTS: The results obtained highlight an inhibitory attitude which cannot be attributed to intellectual insufficiency, but rather to the failed attempt to invest in the intellectual sphere, typical of this age range, owing to the intensity of anguish. Children with cystic fibrosis appear to be at an earlier stage of development, marked by emotive coarctation and the use of adult-type defensive methods, tending towards rationalisation. CONCLUSIONS: Oh the basis of this study, it is possible to detect a danger of disharmonious organisation in the personality structuring process of these children. The hospital must therefore offer adequate psychological support for their psychic evolution.

EEG diagnostic and predictive value on HIV infection in childhood.

This prospective study evaluated the electroencephalographic (EEG) diagnostic and prognostic value in childhood HIV infection. It was carried out on 125 subjects and included all Piemonte's seropositive children. The EEG was repeated every three months during the first 15 months of life, and then, at least, annually in the P1 and P2 group. Data of group P2 was compared blindly to that of the seroconverted control group of the same age and risk. EEG results were normal in P0, P1 and control patients. In group P2, EEG was abnormal in 35.5% of subjects, of these 54.6% developed an encephalopathy with a delay of 2.5 months to 2 years 11 months. EEG is therefore useful to evaluate early CNS damage and to identify onset features and evolution of encephalopathy in P2 patients.