Cross-cultural adaptation and validation of the Italian version of the Montreal Children's Hospital Feeding Scale in a special healthcare needs population.

BACKGROUND: The Montreal Children's Hospital Feeding Scale (MCH-FS) allows paediatricians and other health care professionals to identify feeding difficulties among children. AIM: To translate and adapt the MCH-FS into Italian, and to evaluate the validity and reliability of this Italian version of the Montreal Children's Hospital Feeding Scale (I-MCH-FS). METHODS & PROCEDURES: A total of 150 children with special healthcare needs were admitted to the Rare Disease Unit of the Paediatrics Department at the Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy, between March 2021 and March 2022 (74 males; mean age = 3.85 ± 1.96 years; median age = 4 years; age range = 6 months-6 years and 11 months) and 150 healthy participants (83 males; mean age = 3.5 ± 1.98 years; median age = 3 years; age range = 6 months-6 years and 11 months) were included in the study, which was approved by the local ethics committee. The original version of the MCH-FS was translated and cross-cultural adapted through five stages: (1) initial translation, (2) synthesis of the translations, (3) back translation, (4) expert committee and (5) test of the prefinal version. Test-retest reliability and internal consistency were assessed using Pearson r, Spearman r and Cronbach's alpha, respectively. Construct validity was established by comparing data obtained from patients with those of healthy participants using the Mann-Whitney U-test. OUTCOMES & RESULTS: A Pearson r of 0.98, a Spearman r of 0.95 and Cronbach's alpha value of 0.86 were obtained. In the clinical group, 40.6% children were classified as having feeding disorders (n = 61), while in the normative group 4.7% were diagnosed with feeding problems (n = 7). Mean total score of the clinical group was significatively different from the normative's. CONCLUSIONS & IMPLICATIONS: The I-MCH-FS is a valid and reliable one-page, quick screening tool used to identify feeding disorders among children with special needs in outpatient paediatric setting. WHAT THIS PAPER ADDS: What is already known on the subject The MCH-FS is a valid and reliable parent-report measure aimed at discriminating between children presenting or not feeding disorders. What this paper adds to existing knowledge This paper presents the translation and cross-cultural adaptation of the scale into the Italian language. What are the potential or actual clinical implications of this work? The Italian version of the MCH-FS can be used in the special healthcare needs population.

DiGeorge-like syndrome in a child with a 3p12.3 deletion involving MIR4273 gene born to a mother with gestational diabetes mellitus.

Chromosome 22q11.2 deletion is the most common chromosomal alteration associated with DiGeorge syndrome (DGS), even though this is not the only underlying cause of DGS. In rare patients, mutations in a single gene, TBX1, have been described resulting in a DGS phenotype. Recently, it has been reported that at least part of the TBX1 mutant phenotype is due to excessive bone morphogenetic proteins (BMP) signaling. Evidence suggests that miRNA may modulate the expression of critical T-box transcriptional regulators during midface development and Bmp-signaling. We report on a 7-year-old Caucasian male born to a mother affected with gestational diabetes (GDM) who had a 371Kb-interstitial deletion of 3p12.3 identified by array CGH, involving the ZNF717, MIR1243, and 4273 genes. The child presented with a DiGeorge anomaly (DGA) associated with unilateral renal agenesis and language delay. The immunological evaluation revealed a severe reduction and impairment of T lymphocytes. FISH analysis and TBX1 sequencing were negative. Among the miRNA-4273 predicted target genes, we found BMP3, which is involved in several steps of embryogenesis including kidney and lung organogenesis and in insulin gene expression. Since, DGA is not commonly found in newborns of diabetic mothers, we hypothesize that the pathogenesis of DGA associated with GDM is multifactorial, involving both genetic and/or epigenetic cofactors.

Effects of a combined neuropsychological and cognitive behavioral group therapy on young adults with Fragile X Syndrome: An explorative study.

BACKGROUND: Fragile X Syndrome (FXS) is an X-linked neurodevelopmental disorder that leads to intellectual disability (ID) along with cognitive-behavioral difficulties. Research on psychosocial treatments in individuals FXS and ID is still lacking. This study aimed to investigate the effectiveness of a combined neuropsychological and cognitive behavioral group therapy (nCBT) among young adults with FXS. METHOD: Ten young adults diagnosed with FXS took part in the second stage intervention of "Corp-osa-Mente" (CoM II), a group nCBT program previously outlined by Montanaro and colleagues in an earlier study, with the participants being the same as in the previous research. This report details the outcomes of an additional twelve-month group sections aimed at enhancing the ability to manage emotions and the socio-communicative skills of these young adults. Caregivers completed measures of adaptive functioning, emotional and behavior problems, executive function, communication skills and family quality of life at pre-treatment (T0) and post-treatment (T1). RESULTS: CoM II showed a decrease in depressive and anxiety symptoms from T0 to T1, along with increased socio-pragmatic and communication skills from pre-test to post-test intervention. Additionally, our analysis revealed improvements in the adapative behavior of participants and in the family quality of life. CONCLUSIONS: These preliminary findings suggest that young adults with FXS and ID experienced positive outcomes through participation in CoM II, a group nCBT. However, it is recommended to undertake additional methodologically rigorous studies, such as randomized controlled trials (RCTs), to substantiate these initially promising findings.

Exploring an objective measure of overactivity in children with rare genetic syndromes.

BACKGROUND: Overactivity is prevalent in several rare genetic neurodevelopmental syndromes, including Smith-Magenis syndrome, Angelman syndrome, and tuberous sclerosis complex, although has been predominantly assessed using questionnaire techniques. Threats to the precision and validity of questionnaire data may undermine existing insights into this behaviour. Previous research indicates objective measures, namely actigraphy, can effectively differentiate non-overactive children from those with attention-deficit hyperactivity disorder. This study is the first to examine the sensitivity of actigraphy to overactivity across rare genetic syndromes associated with intellectual disability, through comparisons with typically-developing peers and questionnaire overactivity estimates. METHODS: A secondary analysis of actigraphy data and overactivity estimates from The Activity Questionnaire (TAQ) was conducted for children aged 4-15 years with Smith-Magenis syndrome (N=20), Angelman syndrome (N=26), tuberous sclerosis complex (N=16), and typically-developing children (N=61). Actigraphy data were summarized using the M10 non-parametric circadian rhythm variable, and 24-hour activity profiles were modelled via functional linear modelling. Associations between actigraphy data and TAQ overactivity estimates were explored. Differences in actigraphy-defined activity were also examined between syndrome and typically-developing groups, and between children with high and low TAQ overactivity scores within syndromes. RESULTS: M10 and TAQ overactivity scores were strongly positively correlated for children with Angelman syndrome and Smith-Magenis syndrome. M10 did not substantially differ between the syndrome and typically-developing groups. Higher early morning activity and lower evening activity was observed across all syndrome groups relative to typically-developing peers. High and low TAQ group comparisons revealed syndrome-specific profiles of overactivity, persisting throughout the day in Angelman syndrome, occurring during the early morning and early afternoon in Smith-Magenis syndrome, and manifesting briefly in the evening in tuberous sclerosis complex. DISCUSSION: These findings provide some support for the sensitivity of actigraphy to overactivity in children with rare genetic syndromes, and offer syndrome-specific temporal descriptions of overactivity. The findings advance existing descriptions of overactivity, provided by questionnaire techniques, in children with rare genetic syndromes and have implications for the measurement of overactivity. Future studies should examine the impact of syndrome-related characteristics on actigraphy-defined activity and overactivity estimates from actigraphy and questionnaire techniques.

Case Report: Papillary thyroid carcinoma in Goltz-Gorlin syndrome.

Goltz-Gorlin syndrome (GGS), also known as focal dermal hypoplasia, is a rare X-linked disorder caused by pathogenic variants in the PORCN gene and characterized by several abnormalities, including skin and limb defects, papillomas in multiple organs, ocular malformations, and mild facial dysmorphism. To date, only approximately 300 cases have been described in the literature. A 16-year-old female patient, born with multiple congenital dysmorphisms consistent with GGS and confirmed by genetic exam, was referred to our outpatient clinic for the workup of a thyroid nodule. A thyroid ultrasound showed a bilateral nodular disease with a 17-mm large hypoechoic nodule in the right lobe. Cytological exam of fine needle aspiration biopsy was suspicious for malignancy. Thus, she underwent total thyroidectomy plus lymphadenectomy of the right central compartment. A histological exam disclosed a papillary thyroid carcinoma (PTC) with lymph node micrometastases. Radioiodine (131-Iodine) therapy was performed. At 3- and 6-month follow-up, the patient did not present either ultrasound or laboratory PTC recurrence. To our knowledge, we report the first case of PTC in a patient with GGS. Since thyroid cancer is rare among children and adolescents, we hypothesize that the PORCN pathogenic variant could be responsible for tumor susceptibility. We also provide an overview of the clinical findings on GGS patients already reported and discuss the possible pathogenetic mechanism that may underlie this rare condition, including the role of PORCN in tumor susceptibility.

Concordance of objective and subjective measures of sleep in children with neurodevelopmental conditions: A systematic review and meta-analysis.

The purpose of this systematic review and meta-analysis is to delineate the concordance of objective and subjective measures of sleep in children with neurodevelopmental conditions (NDCs). A systematic literature search identified 31 studies that compare objective and subjective estimates of sleep parameters in autism, ADHD or rare genetic syndromes associated with intellectual disability. The meta-analyses revealed smaller mean differences and larger correlations indicative of greater concordance for parameters associated with sleep scheduling compared to parameters associated with sleep duration and night awakenings. Relative to objective measures, subjective measures produced: 1) greater estimates of total sleep time, sleep efficiency and time in bed; and 2) lower estimates of wake after sleep onset and number of night awakenings. Subgroup analyses also revealed differences in concordance between measurement comparison types (e.g., stronger correlations between actigraphy and sleep diaries, compared to actigraphy and questionnaires) and NDC diagnostic groups. The results predominantly replicate concordance trends observed in typically-developing samples, although some NDC-specific patterns of concordance were identified. This indicates that objective and subjective sleep measures retain broadly similar properties across populations, although researchers and clinicians should be cautious of the impact of NDC-related characteristics on sleep parameter estimates. These findings should inform sleep assessment design and the interpretation of sleep parameter estimates in NDCs, increasing the rigour of sleep parameter description across research and clinical settings.

Rare Genetic Syndromes and Oral Anomalies: A Review of the Literature and Case Series with a New Classification Proposal.

Rare genetic syndromes, conditions with a global average prevalence of 40 cases/100,000 people, are associated with anatomical, physiological, and neurological anomalies that may affect different body districts, including the oral district. So far, no classification of oral abnormalities in rare genetic syndromes is present in the literature. The aim of this narrative review is to analyze literature on rare genetic syndromes affecting dento-oro-maxillofacial structures (teeth, maxillary bones, oral soft tissues, or mixed) and to propose a classification according to the detected oral abnormalities. In addition, five significant cases of rare genetic syndromes are presented. The Scale for the Assessment of Narrative Review Articles (SANRA) was followed for this review. From 674 papers obtained through PubMed search, 351 were selected. Sixty-two rare genetic syndromes involving oral manifestations were found and classified. The proposed classification aims to help the clinician to easily understand which dento-oro-maxillofacial findings might be expected in the presence of each rare genetic syndrome. This immediate framework may both help in the diagnosis of dento-oro-maxillofacial anomalies related to the underlying pathology as well as facilitate the drafting of treatment plans with the involvement of a multidisciplinary team.

Spontaneous neural activity relates to psychiatric traits in 16p11.2 CNV carriers: An analysis of EEG spectral power and multiscale entropy.

Copy number variations (CNV) at the 16p11.2 chromosomal region are rare high-risk CNVs associated with various clinical features and psychiatric disorders including intellectual disability, developmental delays, and autism spectrum disorder. No study to date has investigated whether spontaneous neural activity is altered for 16p11.2 CNV carriers and whether this relates to psychiatric traits. The aim of this study is to examine the impact of 16p11.2 deletions (del) and duplications (dup) on spontaneous neural activity and its relationship to psychiatric problems. EEG was previously collected as part of the Simons Searchlight initiative. Using spectral power (delta, theta, alpha, and beta frequency bands), complexity index (CI), and multiscale entropy analysis techniques, we analyzed frontal resting-state EEG data collected from 22 16p11.2 del carriers, 14 dup carriers, and 13 controls. We then examined associations between neural activity and psychiatric traits, measured with the Child Behavior Checklist. Results indicated that EEG entropy was higher for del and dup compared to controls, respectively, at all timescales. CI was also higher for del and dup compared to controls. Theta power of 16p11.2 dup carriers was higher than controls. A strong association was found between entropy at higher timescales and anxiety problems. In addition, a strong correlation was found between theta power and pervasive developmental problems. Atypical spontaneous neural activity is implicated in 16p11.2 CNVs. With higher entropy or theta power, psychiatric traits increase in severity. Our findings provide evidence of the link between genotype, neural activity, and phenotypes in 16p11.2 CNVs.

Use of a Sodium-Glucose Cotransporter 2 Inhibitor, Empagliflozin, in a Patient with Rabson-Mendenhall Syndrome.

INTRODUCTION: Among the insulin resistance syndromes that lead to diabetes mellitus in young people, Rabson-Mendenhall syndrome (RMS; OMIM # 262190) is an autosomal recessive inherited disease caused by an insulin receptor mutation (INSR; 147,670). Due to the rarity and complexity of the disease, we have few therapeutic alternatives other than insulin with clinical studies with robust evidence. Some reports suggest the adjunct use of metreleptin, metformin, and pioglitazone with improved glycemic control, however, with results still unsatisfactory for the desirable glycemic targets for this age group. CASE PRESENTATION: We report a case of an 11-year-old patient who was diagnosed with RMS at 6 years of age, confirmed through genetic sequencing, with unsatisfactory glycemic control despite the use of >5 IU/kg/day of insulin, pioglitazone, and metformin. To optimize therapy, we used empagliflozin (SGLT2i) to correct hyperglycemia. With the use of the drug, we obtained a decrease of almost 3% in the value of glycated hemoglobin (HbA1c) and about 30% reduction in the total daily dose of insulin. DISCUSSION/CONCLUSION: In this specific case, considering the glycosuric effects independent of the functionality of insulin receptors (which in this case had partial activity due to the INSR gene mutation), an improvement in glycemic control was obtained, with optimization of HbA1c without documented or reported adverse effects. From this isolated case and understanding the pharmacokinetics of this drug class, the question remains whether it would be possible to use this treatment in other situations of SIR where we also have few therapeutic perspectives.