Double somatic mosaicism in Cornelia de Lange syndrome.

Post-zygotic mosaicism is a well-known biological phenomenon characterized by the presence of genetically distinct lineages of cells in the same individual due to post-zygotic de novo mutational events. It has been identified in about 13% of Cornelia de Lange (CdLS) syndrome patients with a molecular diagnosis, an unusual high frequency. Here, we report the case of a patient affected by classic CdLS harboring post-zygotic mosaicism for two different likely pathogenic variants at the same nucleotide position in NIPBL. Double somatic mosaicism has never been reported in CdLS and only rarely recognized in human diseases. Possible pathogenetic mechanisms are discussed.

The impact of catastrophic events on the sex ratio at birth: A systematic review.

OBJECTIVE: The impact of maternal stress on birth outcomes is well established in the scientific research. The sex ratio at birth (SRB), namely the ratio of male to female live births, shows significant alteration when mothers experience acute stress conditions, as proposed by the Trivers-Willard Hypothesis. We aimed to synthetize the literature on the relationship between two exogenous and catastrophic stressful events (natural disasters and epidemics) and SRB. METHODS: A systematic search was run in Scopus, PubMed, Web of Science, and Cochrane Library, until March 9, 2023. The search produced 1336 articles and 25 articles met the inclusion criteria. We found seven case-control studies and 18 observational studies. Most of studies investigated the impact of earthquakes and other natural disasters. Only seven studies examined the effect of epidemics or pandemics. RESULTS: The results of the studies seem inconsistent, as 16 studies found a decline in SRB, three found a rise, four did not record any change and two studies gave contradictory results. The period and population analyzed, the source of information, the method of variance analysis in the SRB, and the failure to assess confounding variables may have influenced the incongruence of the results. CONCLUSION: Our findings contribute to improve the knowledge about the relationship between socio-ecological factors and SRB. Future studies should investigate the mechanisms by which this relationship impacts public health, in particular the health of pregnant women and their newborn, through an accurate and consistent methodology that also includes confounding factors.

The "facie sympathique" sign in hanging: historical background, forensic review, and perspectives.

The "facie sympathique" is a vital sign first described by Etienne Martin in 1899 referring to unilateral miosis, with or without ptosis, at the opposite side from the knot in hanging. This mark is scarcely reported in legal medicine textbooks and scientific papers. Moreover, when cited, it is referred to differently from its original meaning, both as unilateral contraction (miosis) and dilatation (mydriasis) of the pupil depending on the antemortem firmness of the ligature's neck pressure in hanging with little attention to ptosis. Due to the sympathetic nervous pathway supplying the eye, the review of this ocular sign in hanging supports the importance of revitalizing the "facie sympathique" in research on lesion vitality in mechanical asphyxia.

Rock around DYRK1A: Ethnic diversity, clinical challenges.

DYRK1A-related intellectual disability is a recently described syndrome characterized by microcephaly, global developmental delay, impaired speech development, and distinctive facial features, which let to define it as a recognizable syndrome. Here we report four new patients of different ethnicity, broadening the clinical phenotype of the condition and highlighting how ethnic influences in the facial appearance could make it less recognizable.

Healthy orthorexia vs. orthorexia nervosa: Italian validation of the Teruel Orthorexia Scale (TOS).

PURPOSE: Orthorexia nervosa (OrNe) is a potentially pathological condition characterized by a fixation on healthy diet. An increasing number of studies have been conducted on this mental preoccupation, but the validity and reliability of some of the psychometric instruments employed in its assessment are still under debate. Among these measures, the Teruel Orthorexia Scale (TOS) seems to be promising, given that it allows to differentiate between OrNe and other non-problematic forms of interest with healthy eating, named as healthy orthorexia (HeOr). The aim of this study was to examine the psychometric properties of an Italian version of the TOS, by testing its factorial structure, internal consistency, test-retest reliability, and validity. METHOD: Through an online survey, we recruited 782 participants from different regions of Italy, asking them to complete the following self-report instruments: TOS, EHQ, EDI-3, OCI-R, and BSI-18. From the initial sample, 144 participants agreed to complete a second TOS administration 2 weeks later. RESULTS: Data confirmed the validity of the 2-correlated factors structure of the TOS. The questionnaire also showed good reliability, both in terms of internal consistency and temporal stability. With regard to the TOS validity, results showed that OrNe was significantly and positively associated with measures of psychopathology and psychological distress, while HeOr showed no correlations or negative associations with the above-mentioned measures. CONCLUSION: Based on these results, the TOS can be considered a promising measure for the assessment of both pathological and non-problematic forms of orthorexic eating behavior also in Italian population. LEVEL OF EVIDENCE: Level V, descriptive cross-sectional study.

A missense mutation in DDRGK1 gene associated to Shohat-type spondyloepimetaphyseal dysplasia: Two case reports and a review of literature.

Spondylo-epi-metaphyseal dysplasia Shohat type (SEMDSH, OMIM # 602557) is a rare skeletal dysplasia. Until recently, only eight patients of five families have been reported. The disorder is characterized by severely disproportionate short stature with a short neck, small trunk with abdominal distension, and short lower limbs. Joint laxity and bowed legs are seen. The same homozygous splicing pathogenic variant in the DDRGK1 gene was found in four Iraqi families. Here we report a homozygous missense pathogenic variant in DDRGK1 in two children from unrelated two Moroccan families. The clinical and radiological phenotypes of the affected children were similar to those previously described.

Identical EP300 variant leading to Rubinstein-Taybi syndrome with different clinical and immunologic phenotype.

The Rubinstein-Taybi syndrome (RSTS) is a rare developmental disorder characterized by craniofacial dysmorphisms, broad thumbs and toes, intellectual disability, growth deficiency, and recurrent infections. Mutations in the cyclic adenosine monophosphate response element-binding protein (CREB)-binding protein (CREBBP) or in the E1A-associated protein p300 (EP300) genes have been demonstrated in 55% (RSTS1) and up to 8% of the patients (RSTS2), respectively. Dysfunction of immune response has been reported in a subgroup of individuals with RSTS. Here we characterize two patients carrying the same EP300 variant and distinctive RSTS features (including congenital heart abnormalities, short stature, feeding problems, and gastroesophageal reflux). Whole exome sequencing did not support a dual molecular diagnosis hypothesis. Nonetheless, patients showed distinct clinical manifestations and immunological features. The most severe phenotype was associated with reduced T-cell production and diversity. This latter feature was confirmed in a control group of four RSTS patients.

Family history is key to the interpretation of exome sequencing in the prenatal context: unexpected diagnosis of Basal Cell Nevus Syndrome.

OBJECTIVES: To reach a molecular diagnosis for a family with two consecutive fetuses presenting with multiple congenital anomalies. METHODS: The two fetuses underwent prenatal ultrasound, autopsy, radiologic, and genetic investigation. Genetic analysis included karyotype and array-CGH for both fetuses and trio-based whole exome sequencing (WES) only for the second fetus. RESULTS: WES results, initially focusing on recessive or dominant de novo variants, were negative.However, as a result of new relevant information regarding family history, the variant c.648_651dup in the PTCH1 gene was identified as causative of the fetal phenotype. CONCLUSIONS: This case further highlights how WES data analysis and interpretation strongly rely on family history and robust genotype-phenotype correlation. This is even more relevant in the prenatal setting, where access to fetal phenotype is limited and prenatal recognition of many morbid genes is not fully explored. We also provide a detailed description of the prenatal manifestations of Basal Cell Nevus Syndrome.

Childhood maltreatment, personality vulnerability profiles, and borderline personality disorder symptoms in adolescents.

Adverse childhood experiences are significant risk factors in the development of adolescent borderline personality disorder symptoms (BPDs). Theorists have posited that two personality vulnerabilities factors, self-criticism and dependency, may inform our understanding of this relationship. However, no research has examined the associations between early negative experiences, personality vulnerabilities, and adolescent BPDs. The current study aimed to identify profiles of dependency and self-criticism to examine the associations of these profiles with cumulative forms of childhood maltreatment (CM) and BPDs as well as to explore the mediating and moderating role of vulnerable personality profiles in the relationship between cumulative CM and BPDs. Two hundred and forty-one nonclinical and clinical adolescents participated in the study (Mage = 16.37, SD = 1.84). The findings indicated three different profiles: average dependent profile, dependent and self-critical profile, and self-critical profile. Individuals in the average dependent profile presented lower levels of CM and BPDs. Mediation analyses showed that relative to the average dependent profile, a higher cumulative CM history predicted a higher probability of belonging in the dependent and self-critical profile or the self-critical profile and, in turn, this was associated with higher levels of BPDs. No moderating effects of profiles of dependency and self-criticism were found.

The role of eating disorders features, psychopathology, and defense mechanisms in the comprehension of orthorexic tendencies.

PURPOSE: Recent studies pointed out the importance to distinguish orthorexia nervosa (ON) from non-problematic forms of interest with healthy eating. This distinction needs to be further explored since it may favor a better comprehension of the relationship between orthorexic behaviors and psychopathology and lead to an improved understanding of the psychological processes implicated in ON. Therefore, the aim of the current study was to investigate the associations between ON and the core features of eating disorders (EDs), psychopathological symptoms and defense mechanisms, by differentiating three groups of individuals: an ON symptoms group, a healthy-eating control group, and a normal-eating control group. METHODS: College students (n = 270, Mage = 21.57, SD = 2.16) were recruited from Palermo's University, in the south of Italy, and were assigned to three groups: 52 in the ON symptoms group, 157 in the healthy-eating control group and 61 in the normal-eating control group. Participants completed four questionnaires assessing ON (EHQ-21), eating psychopathology (EDI-3), psychopathological symptoms (BSI) and defense mechanisms (DSQ-40). RESULTS: Compared to the control groups, the ON symptoms group reported greater EDs' features, higher psychopathological symptoms and greater employment of different neurotic and immature defense mechanisms. No differences were found between groups with regard to obsessive-compulsive symptoms. CONCLUSION: Our findings support the notion that ON behaviors should be carefully distinguished from non-problematic forms of interest with healthy eating. Indeed, results suggest that ON individuals are characterized by similar clinical features and defensive functioning as those observed in traditional EDs, indicating the importance of deepening our understanding of the relationship between these conditions. LEVEL OF EVIDENCE: Level V, descriptive cross-sectional study.

Age-related differences in the perception of COVID-19 emergency during the Italian outbreak.

OBJECTIVES: Older adults have been identified as a high-risk population for COVID-19, therefore it is crucial to understand how they perceived and reacted to the emergency. We examined age-related differences in emotions, cognitive attitudes, and behavioral responses to the COVID-19 crisis. Based on the Socioemotional Selectivity Theory, we expected to find a positive approach in older adults, which may translate into lower compliance with restrictive measures.Methods: We analyzed data (n = 306) from a nation-wide online survey conducted between April 1st and April 16th, 2020. We compared young (18-29 years), middle-aged (30-50 years), and older (65-85 years) adults' self-reported emotions, attitudes toward the emergency, and compliance with governmental rules.Results: Older adults showed lower negative emotions than young and middle-aged adults. Also, older adults were more confident about COVID-related information received, more favorable toward the restrictive measures, and perceived lower underestimation of the emergency compared to the other age groups. However, older people anticipated a longer time for the emergency to resolve. No age-related differences in compliance with the rules emerged.Conclusion: Older people showed a positive attitude toward the emergency. This attitude was confined in the here and now and did not extend to expectations for the future. Compliance with rules was high across our sample. However, less compliant individuals were also less confident in COVID-related information received by the media and official sources, suggesting the importance of providing precise and reliable information to promote adherence to restrictive measures.

"What's next?" Individual differences in expected repercussions of the COVID-19 pandemic.

The effects of the COVID-19 pandemic on the future are hardly predictable, and people differ in terms of expected repercussions on their future. This study investigated individual differences in the pandemic's expected repercussions, with particular attention to a Balanced Time Perspective (BTP). BTP reflects an individual profile with optimal temporal orientations, it is positively associated with mental health, and it has proven to promote successful coping with unexpected crises. We analyzed data from 3991 adults from 18 to 85 years old participating in an online survey conducted during the Italian lockdown. Participants provided information on BTP, affective states, financial resources, and expectations for the future. Multi-group path analysis was used to test the hypothesized model and to explore gender differences. Results showed that people with a more BTP had fewer negative beliefs about COVID-19's consequences on their future life. BTP affected expected repercussions also indirectly, via affects and beliefs. Finally, gender emerged as a significant moderator of some of the relationships highlighted. The present study contributes to the understanding of the psychological reactions to the current health emergency by confirming its impact on several life domains besides health, not only in the present but also in the anticipated future.

The COVID-19 lockdown and psychological distress among Italian parents: Influence of parental role, parent personality, and child difficulties.

The Italian lockdown following the spread of COVID-19 exposed residents to a long and unexpected period of managing offspring at home. Throughout this time, most parents continued to work remotely. The present research aimed at assessing multiple sociodemographic and psychological variables for parental well-being during the lockdown. An online survey was administered from 6 to 11 April 2020. Respondents were 917 parents aged 23-67 years with up to six children, aged 3-13 years. The measures employed were: 14 demographic questions, the Big Five Inventory (BFI-10), the Emotional Symptoms and Hyperactivity-Inattention subscales of the Strength and Difficulties Questionnaire (SDQ-P), and the General Health Questionnaire (GHQ-12). Multiple moderated linear regression analyses were performed. Motherhood, higher levels of education, higher neuroticism, lower extroversion, and more child emotional and hyperactivity-inattention symptoms were found to be significant predictors of parent distress. Furthermore, a significant two-way interaction between child emotional problems and parent extroversion was found. Overall, parents showed high rates of psychological distress, signalling severe difficulties during the lockdown. Families with a child suffering from emotional and behavioural difficulties should immediately be detected by social services to activate support interventions to prevent chronic and amplified manifestations of these problems.

A Five-Year Survey for Plastic Surgery Malpractice Claims in Rome, Italy.

(1) Introduction: Medical malpractice claims against both health institutions and physicians are a crucial topic in Italy, as well as in other countries, particularly regarding civil proceedings. Our study reports an analysis of all of the malpractice judgments concerning plastic surgery decided in the Civil Court of Rome between 2012 and 2016. (2) Methods: the database of the Observatory Project on Medical Responsibility (ORMe) was analyzed, which collects all of the judgments of the Civil Court of Rome, that is, the first instance district court. Therefore, neither the jurisprudence of the second level court nor that of the Supreme Court was taken into account. (3) Results: 144 judgments concerning plastic surgery were delivered in the five-year period of 2012-2016 (corresponding to 10.6% of total professional liability verdicts of the Civil Court of Rome in the same period). In 101/144 cases (70.14%), the claim was accepted. A total of €4,727,579.00 was paid in compensation for plastic surgery malpractice claims, with a range from a minimum amount of €1555.96 to a maximum amount of €1,425,155.00 and an average compensation of €46,807.71 per claim that was significantly lower compared to other surgical disciplines. (4) Conclusions: Our data confirm that the analyzed branch has a high litigation rate, with a prevalence of convictions for cosmetic procedures over reconstructive ones, both for malpractice and for violation of the informed consent. Plastic surgery is also confirmed among those branches in which the professionals are more frequently sued compared to health institutions.

PIGW-related glycosylphosphatidylinositol deficiency: Description of a new patient and review of the literature.

Inherited glycosylphosphatidylinositol (GPI) deficiencies are a group of clinically and genetically heterogeneous conditions belonging to the congenital disorders of glycosylation. PIGW is involved in GPI biosynthesis and modification, and biallelic pathogenic variants in this gene cause autosomal recessive GPI biosynthesis defect 11. Only five patients and two fetuses have been reported in the literature thus far. Here we describe a new patient with a novel homozygous missense variant in PIGW, who presented with hypotonia, severe intellectual disability, early-onset epileptic seizures, brain abnormalities, nystagmus, hand stereotypies, recurrent respiratory infections, distinctive facial features, and hyperphosphatasia. Our report expands the phenotype of GPI biosynthesis defect 11 to include stereotypies and recurrent respiratory infections. A detailed and long-term analysis of the electroclinical characteristics and review of the literature suggest that early-onset epileptic seizures are a key manifestation of GPI biosynthesis defect 11. West syndrome and focal-onset epileptic seizures are the most common seizure types, and the fronto-temporal regions may be the most frequently involved areas in these patients.

Parenting-Related Exhaustion During the Italian COVID-19 Lockdown.

OBJECTIVE: Worldwide, the coronavirus disease 2019 (COVID-19) pandemic has generated significant worry, uncertainty, anxiety, sadness, and loneliness. In Italy, these effects have been particularly pronounced. While research on the COVID-19 outbreak has mainly focused on the clinical features of infected patients and the psychological impact on the general population and health professionals, no investigation has yet assessed the psychological impact of the pandemic on parents. In the present research, we conducted a web-based survey of Italian parents to examine the prevalence of parenting-related exhaustion-and to identify its associated risk and protective factors-4 weeks into the lockdown. METHODS: A total of 1,226 parents provided their consent to participate in the study and completed a demographic questionnaire, information relating to particular COVID-19 experiences, and measures of emotional exhaustion, parental resilience, social connections, and psychological distress during the lockdown. RESULTS: Seventeen percent of our sample experienced significant parenting-related exhaustion, with mothers more severely affected. Multiple regression analyses showed that greater parenting-related exhaustion was predicted by psychological distress, lower parental resilience, motherhood, fewer perceived social connections, and being single, as well as having a child with special needs, having a large number of children, and having younger children. CONCLUSION: The findings add further support to the call for preventive programs to support parents throughout the COVID-19 pandemic. Mental health professionals and social workers should be warned of the effects of lockdown and social distancing on parenting and, consequently, the well-being of children.

Diagnostic Yield of an Algorithm for Neonatal and Infantile Cholestasis Integrating Next-Generation Sequencing.

OBJECTIVE: To evaluate the performance of a diagnostic protocol for neonatal/infantile cholestasis in which the main clinical patterns steered the early use of different genetic testing strategies. STUDY DESIGN: An observational study was conducted between 2012 and 2017 in a tertiary care setting on a prospective cohort of children with cholestasis occurring at ≤1 year of age and persisting ≥6 weeks, to measure the detection rate of underlying monogenic diseases. After the exclusion of biliary atresia, a clinically driven genetic testing was performed, entailing 3 different approaches with different wideness: confirmatory single-gene testing; focused virtual panels; and wide search through trio whole-exome sequencing. RESULTS: We enrolled 125 children (66 female, median age 2 months); 96 (77%) patients had hypocholic stools and were evaluated rapidly to exclude biliary atresia, which was the final diagnosis in 74 (59%). Overall, 50 patients underwent genetic testing, 6 with single confirmatory gene testing, 38 through panels, and 6 with trio whole-exome sequencing because of complex phenotype. The genetic testing detection rate was 60%: the final diagnosis was Alagille syndrome in 11, progressive familial intrahepatic cholestasis type 2 in 6, alpha-1-antitrypsin deficiency in 3, and progressive familial intrahepatic cholestasis type 3 in 2; a further 7 genetic conditions were identified in 1 child each. Overall, only 18 of 125 (14%) remained with an indeterminate etiology. CONCLUSIONS: This protocol combining clinical and genetic assessment proved to be an effective diagnostic tool for neonatal/infantile cholestasis, identifying inherited disorders with a high detection rate. It also could allow a noninvasive diagnosis in children presenting with colored stools.

Anxiety and depression among adult amputees: the role of attachment insecurity, coping strategies and social support.

A number of studies have investigated the role of coping and social support as protective factors for psychosocial adjustment after amputation. In contrast, few have focused on the role of attachment styles. Therefore, the purpose of this study was to examine the relationship between attachment insecurity, social support, coping strategies and negative emotions, such as anxiety and depression, in adult amputees. Sixty-two amputated adults (71% males, 29% females), recruited from the Prosthetic Centre of the Italian Workers' Compensation Authority, completed the Attachment Style Questionnaire, the Coping Inventory for Stressful Situations, the Multidimensional Scale of Perceived Social Support, the Beck Depression Inventory II and the State-Trait Anxiety Inventory Y. Based on Pearson's correlations results, we conducted a mediation analysis to examine whether the association between attachment insecurity (i.e., attachment anxiety and attachment avoidance) and negative emotion (i.e. depression, state anxiety and trait anxiety) variables was mediated by emotion-oriented coping. Analyses revealed the role of insecure attachment styles in influencing the use of an emotion-oriented coping strategy in particular. The latter mediated the relationship between attachment insecurity, depression and anxiety in adult amputees.

Atypical presentation of pediatric BRAF RASopathy with acute encephalopathy.

We report a 9-year-old girl with hypotonia, severe motor delay, absent speech, and facial dysmorphism who developed acute encephalopathy with severe neurological outcome. Trio-based whole exome sequencing (WES) analysis detected a de novo heterozygous mutation in the BRAF gene leading to the diagnosis of an atypical presentation of cardiofaciocutaneous (CFC) syndrome. This is the second case of CFC syndrome complicated with acute encephalopathy reported in the literature and supports the hypothesis that acute encephalopathy might be one of the complications of the syndrome due to an intrinsic susceptibility to this acute event. The report furthermore highlights the role of WES in providing a fast diagnosis in patients in critical conditions with atypical presentation of rare genetic syndromes.

Expanding the phenotype of MED 17 mutations: Description of two new cases and review of the literature.

We report the case of two siblings presenting with failure to thrive in early years, progressive microcephaly, moderate intellectual disability, developmental delay, ataxic gait and seizures with an identical EEG pattern, and minimal cerebellar atrophy. We ruled out the syndromic and metabolic causes of microcephaly and subsequently conducted a panel of genetic diagnostic tests, including the clinical exome sequencing which revealed compound heterozygous mutations in MED 17 gene in both patients. p.Glu16fs was found to be inherited from the mother and p.Gly253Arg from the father. This case along with review of the literature suggests that mutations in MED17 may define a phenotype characterized by progressive microcephaly, intellectual disability, seizures, cerebellar atrophy of variable degree, and ataxia. More cases are needed to define the phenotype-genotype correlation in MED17 mutations. However, basing on our findings, we recommend testing MED17 mutations in any patient presenting with two or more of the aforementioned signs and symptoms.