22q11 Deletion Research Articles

SAT086 Early-onset HNF1B-MODY With Persistent Insulin Requirement In A 2-year-old Female

Abstract Disclosure: F. Ighalo: None. S.R. Kelly: None. M. Tosur: None. M.E. Craven: None. Introduction: Diabetes related to HNF1B pathogenic variants or deletions (maturity-onset diabetes of the young 5 [MODY 5]) typically presents in adolescence or early adulthood, with a median age of 20 years. Bustamante et al. previously described two patients with 17q12 deletion encompassing HNF1B presenting with diabetes and pre-diabetes before the age of 3, who were managed with dietary intervention alone without insulin requirement. This case describes a 2-year-old diagnosed with HNF1B-MODY after developing hyperglycemia in the setting of an acute illness, who continued to require insulin therapy following recovery. Clinical Case: A 2-year-old female with a history of recurrent viral infections and failure to thrive was admitted to the intensive care unit in hypovolemic shock due to hemolytic uremic syndrome due to Shiga toxin. On hospital day 7, while on supraphysiologic steroid doses, she developed hyperglycemia with glucoses above 600 mg/dL. She required an insulin drip to maintain blood glucoses between 100 and 200 mg/dL. Her four-month hospital stay was complicated by cardiogenic shock requiring extracorporeal mechanical oxygenation, renal failure requiring hemodialysis, respiratory failure resulting in a tracheostomy, and dysphagia resulting in a gastrostomy tube. During this time, she continued to require insulin despite being weaned off steroids and transitioning from total parenteral nutrition to gastrostomy tube feeds. Her hemoglobin A1c one month post-diagnosis was 4.9%, and continued to rise to 6.6% and 7.6% at 3 and 4 months post-diagnosis, respectively. Testing for islet autoantibodies was negative. A chromosomal microarray analysis revealed a micro-deletion in chromosome 17q12 that included the HNF1B gene. MRI showed a near total absent pancreas, and multiple small cysts scattered throughout both kidneys. She also had fecal elastase levels in the insufficient range (135 mcg/g, normal >200 mcg/g). Six weeks after the start of insulin drip, she was transitioned from an insulin drip to subcutaneous insulin injections, and eventually placed on an insulin pump prior to discharge. With continued clinical improvement, her insulin doses decreased, but she was not able to come off insulin completely. She had gradual decline in her insulin requirements from 1.0 units/kg/day down to 0.1 units/kg/day at time of discharge. Her current insulin requirement at 6 months post-diagnosis is 0.2 units/kg/day. Conclusion: This case represents the rare development of diabetes before adolescence in HNF1B-MODY, and one of the most severe presentations seen in a prepubertal child requiring persistent insulin therapy at 6 months post-diagnosis. Potential contribution of complicated hospital course on persistent insulin requirement in the setting of 17q12 micro-deletion cannot be excluded. Presentation: Saturday, June 17, 2023

Incidental finding at methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA): how to proceed?

Introduction: Since the advent of new generation sequencing, professionals are aware of the possibility of obtaining findings unrelated to the pathology under study. However, this possibility is usually forgotten in the case of studies aimed at a single gene or region. We report a case of a 16-month-old girl with clinical suspicion of Silver-Russell syndrome (SRS). Methods: Following the international SRS consensus, methylation alterations and copy number variations (CNVs) at 11p15 region and maternal uniparental disomy of chromosome 7 were analysed and discarded by MS-MLPA. Results: Unexpectedly, the 11p15 region MS-MLPA showed a decrease in the signal of a copy number reference probe. Deletions affecting a single probe are inconclusive. So, we faced the ethical dilemma of whether it was appropriate to confirm this alteration with independent techniques and to offer a diagnostic possibility that was in no way related to clinical suspicion. Fortunately, in this particular case, the informed consent had not been specific to a particular pathology but to any disorder associated with growth failure. Performed alternative studies allowed the final diagnosis of 22q deletion syndrome. Conclusion: We demonstrate the importance of informing patients about the possibility of obtaining incidental findings in genetic techniques (not only in next generation sequencing) during pre-test genetic counselling consultations. In addition, we highlight the relevance of including in the informed consent the option of knowing these unexpected incidental findings as in some cases, this will help to elucidate the definitive diagnosis and provide the correct follow-up and treatment.

Interrupted aortic arch in children: An in-depth look at etiology, embryological mechanisms, and morphology (a literature review)

Relevance: Congenital heart defects (CHD) account for one-third of all congenital malformations and occur in 0.7-1.7% of newborns. Interrupted aortic arch (IAA) is quite rare, accounting for 1% of CHD. IAA is an unusual shape of critical neonatal heart disease in which there is a lack of continuity between the ascending aorta and the descending thoracic aorta. IAA is almost always severe in the neonatal period and requires urgent corrective surgery.This study aimed to identify gaps in knowledge, suggest directions for in-depth research through critical analysis, and improve our understanding of risk factors and mechanisms of embryology that contribute to aortic arch interruption to improve the approach to diagnosis and treatment.Materials and Methods: A literature search was conducted in electronic databases PubMed, MEDLINE, Web of Science, Google Scholar, and e-library. The review covered 20 sources meeting the inclusion criteria.Results: We systematize the available literature data on embryology and risk factors to improve the IAA diagnosis and treatment approach. We found that aorta development begins at Week 3 of pregnancy, and the main factor in further IAA etiology is the chromosomal deletion 22q11.2.Conclusion: Understanding the timeline during early embryonic development plays a critical role in aortic arch formation. Abnormalities occurring in this period, such as chromosomal deletions, may contribute to IAA. This finding highlights the importance of genetic factors in the etiology of this condition and the potential for genetic screening and counseling for individuals with chromosomal abnormalities, especially those in the 22q11.2 region.

Risk factors for Microtia and preventive approaches

Microtia is a congenital anomaly that directly affects the external ear. Although the etiology of this pathology is not fully elucidated, there are several factors that are associated with its occurrence, such as genetics, perinatal and maternal conditions. During organogenesis of the outer ear it is important to mention that as anomalies occur before the sixth week of pregnancy, the chances of severe defects or total absence of the outer ear increase. At the genetic level, the etiology of microtia has been related to multiple causes, as well as the identification of genes involved in allelic expression pathways and transcription factors. Furthermore, this anomaly does not always occur alone, but associated with other pathologies such as cleft palate (12.8%), cleft lip and palate (11.5%), anophthalmia/microphthalmia (11.5%), facial asymmetry (10.6%), as well as oculoauriculovertebral spectrum syndromes, Goldenhar syndrome, craniofacial microsomia, Treacher Collins syndrome, Nager, DiGeorge or 22q deletion, Townes-Brock syndrome and branchi oto-renal syndrome. Treatments are based on the aesthetic management of the patient, but also related to the improvement of the patient's hearing ability. Epidemiologically, the prevalence ranges from 0.8 to 17.5 per 10,000 live births. One of the main risk factors for variation in case identification is altitude, genetics and maternal-perinatal factors. This literature review provides a thorough analysis of information for the better understanding, analysis and clinical management of this congenital anomaly.

Adaptive behaviour deficits in individuals with 3q29 deletion syndrome.

3q29 deletion syndrome (3q29del) is associated with a significantly increased risk for neurodevelopmental and neuropsychiatric phenotypes. Mild to moderate intellectual disability (ID) is common in this population, and previous work by our team identified substantial deficits in adaptive behaviour. However, the full profile of adaptive function in 3q29del has not been described nor has it been compared with other genomic syndromes associated with elevated risk for neurodevelopmental and neuropsychiatric phenotypes. Individuals with 3q29del (n=32, 62.5% male) were evaluated using the Vineland Adaptive Behaviour Scales, Third Edition, Comprehensive Parent/Caregiver Form (Vineland-3). We explored the relationship between adaptive behaviour and cognitive function, executive function, and neurodevelopmental and neuropsychiatric comorbidities in our 3q29del study sample, and we compared subjects with 3q29del with published data on fragile X syndrome, 22q11.2 deletion syndrome and 16p11.2 deletion and duplication syndromes. Individuals with 3q29del had global deficits in adaptive behaviour that were not driven by specific weaknesses in any given domain. Individual neurodevelopmental and neuropsychiatric diagnoses had a small effect on adaptive behaviour, and the cumulative number of comorbid diagnoses was significantly negatively associated with Vineland-3 performance. Both cognitive ability and executive function were significantly associated with adaptive behaviour, and executive function was a better predictor of Vineland-3 performance than cognitive ability. Finally, the severity of adaptive behaviour deficits in 3q29del was distinct from previously published data on comparable genomic disorders. Individuals with 3q29del have significant deficits in adaptive behaviour, affecting all domains assessed by the Vineland-3. Executive function is a better predictor of adaptive behaviour than cognitive ability in this population and suggests that interventions targeting executive function may be an effective therapeutic strategy.

Genetics of kidney disorders in Phelan-McDermid syndrome: evidence from 357 registry participants.

Phelan-McDermid syndrome (PMS) is a rare genetic disorder caused by SHANK3 pathogenic variants or chromosomal rearrangements affecting the chromosome 22q13 region. Previous research found that kidney disorders, primarily congenital anomalies of the kidney and urinary tract, are common in people with PMS, yet research into candidate genes has been hampered by small study sizes and lack of attention to these problems. We used a cohort of 357 people from the Phelan-McDermid Syndrome Foundation International Registry to investigate the prevalence of kidney disorders in PMS using a cross-sectional design and to identify 22q13 genes contributing to these disorders. Kidney disorders reported included vesicoureteral reflux (n = 37), hydronephrosis (n = 36), dysplastic kidneys (n = 19), increased kidney size (n = 19), polycystic kidneys (15 cases), and kidney stones (n = 4). Out of 315 subjects with a 22q13 deletion, 101 (32%) had at least one kidney disorder, while only one out of 42 (2%) individuals with a SHANK3 pathogenic variant had a kidney disorder (increased kidney size). We identified two genomic regions that were significantly associated with having a kidney disorder with the peak associations observed near positions approximately 5Mb and 400Kb from the telomere. The candidate genes for kidney disorders include FBLN1, WNT7B, UPK3A, CELSR1, and PLXNB2. This study demonstrates the utility of patient registries for uncovering genetic contributions to rare diseases. Future work should focus on functional studies for these genes to assess their potential pathogenic contribution to the different subsets of kidney disorders.

Musculoskeletal phenotypes in 3q29 deletion syndrome.

3q29 deletion syndrome (3q29del) is a rare genomic disorder caused by a 1.6 Mb deletion (hg19, chr3:195725000-197350000). 3q29del is associated with neurodevelopmental and psychiatric phenotypes, including an astonishing >40-fold increased risk for schizophrenia, but medical phenotypes are less well-described. We used the online 3q29 registry of 206 individuals (3q29deletion.org) to recruit 57 individuals with 3q29del (56.14% male) and requested information about musculoskeletal phenotypes with a custom questionnaire. 85.96% of participants with 3q29del reported at least one musculoskeletal phenotype. Congenital anomalies were most common (70.18%), with pes planus (40.35%), pectus excavatum (22.81%), and pectus carinatum (5.26%) significantly elevated relative to the pediatric general population. 49.12% of participants reported fatigue after 30 min or less of activity. Bone fractures (8.77%) were significantly elevated relative to the pediatric general population. Participants commonly report receiving medical care for musculoskeletal complaints (71.93%), indicating that these phenotypes impact quality of life for individuals with 3q29del. This is the most comprehensive description of musculoskeletal phenotypes in 3q29del to date, suggests ideas for clinical evaluation, and expands our understanding of the phenotypic spectrum of this syndrome.

Neurodegeneration or dysfunction in Phelan-McDermid syndrome? A multimodal approach with CSF and computational MRI

BackgroundPhelan-McDermid syndrome (PMS) is a rare multisystem disease with global developmental delay and autistic features. Genetically, the disease is based on a heterozygous deletion of chromosome 22q13.3 with involvement of at least part of the SHANK3 gene or heterozygous pathogenic variants in SHANK3. Pathophysiologically, this syndrome has been regarded as a synaptopathy, but current data suggest an additional concept, since axonal functions of neurons are also impaired, thus, the specific pathophysiological processes in this disease are not yet fully understood. Since symptoms of the autism spectrum, regression, and stagnation in development occur, we investigated whether neuroinflammatory and neurodegenerative processes may also play a role. To this end, we analysed biomarkers in cerebrospinal fluid (CSF) and parameters from magnetic resonance imaging with high-resolution structural T1w volumetry and diffusion tensor imaging analysis in 19 Phelan-McDermid syndrome patients.ResultsCSF showed no inflammation but abnormalities in tau protein and amyloid-ß concentrations, however, with no typical biomarker pattern as in Alzheimer’s disease. It could be demonstrated that these CSF changes were correlated with integrity losses of the fibres in the corticospinal tract as well as in the splenium and dorsal part of the cingulum. High CSF levels of tau protein were associated with loss of integrity of fibres in the corticospinal tract; lower levels of amyloid-ß were associated with decreasing integrity of fibre tracts of the splenium and posterior cingulate gyrus. Volumetric investigations showed global atrophy of the white matter, but not the grey matter, and particularly not in temporal or mesiotemporal regions, as is typical in later stages of Alzheimer’s disease.ConclusionsIn summary, alterations of neurodegenerative CSF markers in PMS individuals could be demonstrated which were correlated with structural connectivity losses of the corticospinal tract, the splenium, and the dorsal part of the cingulum, which can also be associated with typical clinical symptoms in these patients. These findings might represent a state of dysfunctional processes with ongoing degenerative and regenerative processes or a kind of accelerated aging. This study should foster further clinical diagnostics like tau- and amyloid-PET imaging as well as novel scientific approaches especially in basic research for further mechanistic proof.

Cross-species analysis identifies mitochondrial dysregulation as a functional consequence of the schizophrenia-associated 3q29 deletion.

The 1.6-megabase deletion at chromosome 3q29 (3q29Del) is the strongest identified genetic risk factor for schizophrenia, but the effects of this variant on neurodevelopment are not well understood. We interrogated the developing neural transcriptome in two experimental model systems with complementary advantages: isogenic human cortical organoids and isocortex from the 3q29Del mouse model. We profiled transcriptomes from isogenic cortical organoids that were aged for 2 and 12 months, as well as perinatal mouse isocortex, all at single-cell resolution. Systematic pathway analysis implicated dysregulation of mitochondrial function and energy metabolism. These molecular signatures were supported by analysis of oxidative phosphorylation protein complex expression in mouse brain and assays of mitochondrial function in engineered cell lines, which revealed a lack of metabolic flexibility and a contribution of the 3q29 gene PAK2. Together, these data indicate that metabolic disruption is associated with 3q29Del and is conserved across species.

Bridging the Communication Gap Between People With Cognitive Impairments and Their Caregivers Using mHealth Apps: User-Centered Design and Evaluation Study With People With 22q11 Deletion Syndrome.

In families with children with cognitive impairments, both parents and children experience tension and have questions because of a lack of communication and adequate information. Therefore, there is a great need to develop tools that can help bridge the communication gap between patients and caregivers by stimulating conversations and providing psychoeducational tools. mHealth apps show great potential in this context. The objective of this research is to discover the specific ways young people with cognitive impairments and their families interact with mHealth apps in the context of bridging the communication gap. This newly discovered information leads to potentially more impactful mHealth interventions in the future. Therefore, this paper documents the design and development of a mHealth app for a specific group of people with cognitive impairments-people with 22q11 deletion syndrome (22q11 DS)-and their caregivers, as well as key learnings from the evaluation of this app. An iterative, user-centered design approach is used to design and develop the app. Design and evaluation happens in 2 phases. During the design phase, feedback is gathered from 2 medical experts and 3 human computer interaction (HCI) experts using a low-fidelity paper prototype. During the evaluation phase, feedback is gathered from 8 families with a child with 22q11 DS using a fully working proof of concept. This phase consists of a semistructured interview, a 2-4-week trial period, and a concluding semistructured interview. The evaluation results of the fully working proof of concept led to design recommendations related to four different topics: (1) overcoming usage barriers, (2) stimulating conversation through a mHealth app, (3) providing information, and (4) bringing continual added value. Results are presented according to six different categories obtained in a thematic analysis: (1) feedback about the app "as is," (2) difficulties, (3) comparison between physical and digital tool, (4) extensions, (5) intention, and (6) other. In this research, the need for apps that help bridge the communication gap between a person with cognitive impairment and their caregiver is confirmed. All participating families express their gratitude and mention the added value for other families. Therefore, it is highly encouraged for clinics and institutions to take action and develop an app to be used in practice. Furthermore, considerations when developing for people with 22q11 DS, or more broadly, people with cognitive impairments, are proposed. First, one should keep design principles in mind to overcome usage barriers. Next, recognition is a key concept when stimulating conversations through mobile apps. Third, information should be provided by a trusted source, and more than just clinical information can be considered valuable. Finally, having the possibility of using a digital tool that can be personalized brings continual added value.

Genetic Spectrum of Congenital Anomalies of the Kidney and Urinary Tract in Chinese Newborn Genome Project

Congenital anomalies of the kidney and urinary tract (CAKUT) corresponds to a spectrum of defects. Several large-cohort studies have used high-throughput sequencing to investigate the genetic risk of CAKUT during antenatal, childhood, and adulthood period. However, our knowledge of newborns with CAKUT is limited. This multicenter retrospective cohort study explored the genetic spectrum of CAKUT in a Chinese neonatal cohort. Clinical data and whole exome sequencing (WES) data of 330 newborns clinically diagnosed with CAKUT were collected. WES data were analyzed for putative deleterious single nucleotide variants (SNVs) and potential disease-associated copy number variants (CNVs). In this study, pathogenic variants were identified in 61 newborns (18.5%, 61/330), including 35 patients (57.4%) with SNVs, 25 patients (41%) with CNVs, and 1 patient with both an SNV and a CNV. Genetic diagnosis rates were significantly higher in patients with extrarenal manifestations (P＜0.001), especially in those with cardiovascular malformations (P＜0.05). SNVs in genes related to syndromic disorders (CAKUT with extrarenal manifestations) were common, affecting 20 patients (57.1%, 20/35). KMT2D was the most common gene (5 patients) and 17q12 deletion was the most common CNV (4 patients). Patient 110 was detected with both a CNV (17q12 deletion) and an SNV (a homozygous variant of SLC25A13). Among the newborns with positive genetic results, 22 (36.1%, 22/61) patients may benefit from a molecular diagnosis and change in clinical management (including early multidisciplinary treatment, disease-specific follow-up, and familial genetic counseling). This study shows the heterogeneous genetic etiologies in a Chinese CAKUT neonatal cohort by using WES. Patients with CAKUT who have extrarenal manifestations are more likely to harbor genetic diagnoses. Kabuki syndrome and 17q12 deletion syndrome were the most common genetic findings. Approximately 36.1% of the patients may benefit from molecular diagnoses and a change in clinical management.

Polysomnographic findings in children with 22q deletion & duplication syndrome: relationship to genetic diagnosis, parent-reported symptoms, and calcium levels.

22q11.2 deletion syndrome (22q11.2DS) is the most common microdeletion syndrome. In the current study, we assessed the relationship between parent-reported symptoms of obstructive sleep apnea (OSA) and polysomnographic (PSG) results in patients with 22q11.2DS. Additionally, we explored the relationships between genetic diagnosis, serum calcium and ferritin levels, and PSG results. Retrospective chart review was completed for patients enrolled in our 22q Center's registry from 2015-2021. Data extracted included: patient characteristics, parent-reported sleep symptoms from the Childhood Sleep Habits Questionnaire (CSHQ), serum calcium and ferritin levels, and results from formal PSG. Overall, n = 89 encounters (60 unique patients) with PSG data demonstrated that there were no differences in OSA between those with deletion vs duplication, but PLMD was more common in those with deletion (35% vs 7%, p = 0.032). In a subset of n = 24 encounters with PSG and survey data in proximity, there were no significant associations between the CSHQ sleep-disordered breathing subscale and OSA presence or severity (p = 0.842). Likewise, we found no significant associations between the individual symptoms of OSA and PSG results (all p > 0.5). In those patients with available calcium (n = 44) and ferritin (n = 17) levels, we found a significant negative correlation between serum calcium and PLMS (r = -0.446, p = 0.002), but not ferritin (r = -0.067, p = 0.797) levels. Parent-reported symptoms do not predict the presence or severity of OSA in children with 22q11.2DS. There was a negative correlation between serum calcium, but not ferritin, and PLMS on PSG.

Prospective phenotyping of CHAMP1 disorder indicates that coding mutations may not act through haploinsufficiency

CHAMP1 disorder is a genetic neurodevelopmental condition caused by mutations in the CHAMP1 gene that result in premature termination codons. The disorder is associated with intellectual disability, medical comorbidities, and dysmorphic features. Deletions of the CHAMP1 gene, as part of 13q34 deletion syndrome, have been briefly described with the suggestion of a milder clinical phenotype. To date, no studies have directly assessed differences between individuals with mutations in CHAMP1 to those with deletions of the gene. We completed prospective clinical evaluations of 16 individuals with mutations and eight with deletions in CHAMP1. Analyses revealed significantly lower adaptive functioning across all domains assessed (i.e., communication, daily living skills, socialization, and motor skills) in the mutation group. Developmental milestones and medical features further showed difference between groups. The phenotypes associated with mutations, as compared to deletions, indicate likely difference in pathogenesis between groups, where deletions are acting through CHAMP1 haploinsufficiency and mutations are acting through dominant negative or gain of function mechanisms, leading to a more severe clinical phenotype. Understanding this pathogenesis is important to the future of novel therapies for CHAMP1 disorder and illustrates that mechanistic understanding of mutations must be carefully considered prior to treatment development.

An online survey to understand the needs of caregivers of family members with 22q11 deletion syndrome.

Most individuals with 22q11.2 deletion syndrome (22q11DS) have multi-system and lifelong needs requiring substantial support. Their primary caregivers are usually family members who dedicate lifelong time and effort to their role. The pressures of their roles can negatively impact caregivers' psychosocial well-being, suggesting a need for additional support for this community who currently have no specialised interventions available. This online study surveyed 103 caregivers of family members with 22q11DS to determine the barriers to accessing support that they faced, the kind of support they would value and whether an online intervention could meet their needs. The caregivers indicated that a brief online intervention focused on teaching practical skills and connecting them with a peer network of support would be most valuable. Future studies are planned that will build on these results by designing and testing online interventions tailored to this community.

Severe Hypocalcemia in the Adolescent as the Only Manifestation of <i>22q11</i> Microdeletion Syndrome: Clinical Case

Background. In this article, we would like to describe the atypical clinical picture and course of 22q11 microdeletion syndrome in a patient without specific phenotypic signs and symptoms typical for this disease.Clinical case description. Male patient, 13 years old, was hospitalized for the first time with seizure and multiple spinal fractures caused by hypocalcemia. He was referred to rheumatologist and clinical geneticist after hospital stay. Differential diagnosis included not only various bones metabolic diseases, but also 22q11 deletion syndrome. Later it was confirmed via FISH test.Conclusion. This clinical case proves once again the uniqueness of every single case, as well as the importance of comprehensive approach to the diagnosis and management of such patients.

Tracheostomy experiences in chronic respiratory failure after congenital heart surgery

Introduction
 A small number of children with repaired congenital heart defects may require a tracheostomy for ongoing ventilatory support. Congenital airway anomalies, laryngomalacia, postoperative airway complications and genetic syndromes associated with airway and facial anomalies, such as DiGeorge Syndrome (22q11 deletion), can be counted among the reasons why patients are unable to be weaned from the ventilator. In this study, we aimed to define the outcomes of patients who required a tracheostomy due to chronic respiratory failure after congenital heart surgery, and the existing risk factors for in-hospital and post-discharge mortality.
 Materials and methods
 The files of 1382 patients who underwent surgery due to CHD in the Pediatric Cardiovascular Surgery Clinic in ……………., between February 2019 and February 2023, were retrospectively scanned. Patients’ age, gender, body weight, cardiac diagnosis, surgical intervention, length of stay in the intensive care unit, number of extubation attempts, total length of stay on the ventilator, need for ventilator at discharge, rates of weaning from tracheostomy and time of weaning from tracheostomy and mortality rates, were obtained from patient files and hospital database.
 Results
 Tracheostomy was performed in 15 of 1382 patients who underwent surgery during the four year study period. Mean (SD) duration of ventilation prior to tracheostomy was 35 days (IQR= 19 – 47). The median follow up time in patients was 224 days (IQR=116-538). Three patients were decannulated and six had died. Causes of death in six patients included sepsis (2), cardiac instability (1), neurological complications (2) and pulmonary haemorraghia (1). 
 The median time to discharge after tracheostomy in patients was 51 days (IQR= 33.50 – 147). 
 Eight patients (53.3%) were discharged on home ventilation. Causes of deaths were often multifactorial for children who died during their initial hospital stay. Mortality was seen in six patients, a rate of 40%. 
 Conclusion
 The need for tracheostomy after cardiac surgery plays an important role in early and late mortality in children. Ventilator-dependent chronic respiratory failure is the most common cause of childhood tracheostomies. We believe that determining the optimal timing for tracheostomy in the pediatric population will be effective in reducing prolonged ventilation and tracheostomy-related morbidities.

Description of Neuropsychological Profile in Patients with 22q11 Syndrome

Background: 22q11 deletion syndrome (SD22Q11) is a neurogenetic condition that is associated with a high risk of neurodevelopmental disorders and intellectual disability. People with SD22Q11, both children and adults, often experience significant difficulties in social interactions, as well as neurocognitive deficits, and have elevated rates of autism spectrum disorder (ASD). Despite this, the relationship between basic cognitive processes and cognitive ability in this population has not been well investigated. Methods: the main objective of the present research is to describe the neurocognitive profile of people with SD22Q11 using standardized neuropsychological assessment instruments. For this purpose, a sample of 10 participants aged between 7 and 15 years was administered an assessment battery with the following tests: WISC-V, CELF-5, NEPSY-II, CSAT-R, CARAS-R, TP, MABC-2, BRIEF-2, SENA, DABAS, ABAS-II, SCQ, and ADOS-2. Results: the results showed IQ scores in the borderline normal range, as well as difficulties in language functions, social skills, motor skills, and executive functions. Conclusions: an individualized assessment taking into account the globality of its expression, and a therapeutic approach adapted to the specific needs of children with this syndrome is essential.

Visual-Motor Integration Deficits in 3q29 Deletion Syndrome

3q29 deletion syndrome (3q29del) is associated with neuropsychiatric and neurodevelopmental phenotypes. We previously reported that graphomotor weakness is present in up to 78% of individuals with 3q29del. We have now explored nuances of the graphomotor phenotype and its association with other comorbidities in this population. Participants were recruited from the online 3q29 registry (3q29deletion.org) for two days of deep phenotyping. 32 individuals with 3q29del (62.5% male) were evaluated with the Beery-Buktenica Developmental Test of Visual-Motor Integration (VMI) to assess visual-motor integration. Participants were also evaluated with measures of cognitive ability, executive function, adaptive behavior, and school function. Males with 3q29del performed significantly worse than females on the VMI and Motor Coordination subtest. VMI performance was significantly associated with ADHD diagnosis and cognitive ability. Compared to published data from individuals with 22q11.2 deletion syndrome, individuals with 3q29del showed significantly more impairment. The 3q29 deletion is associated with substantial deficits in visual-motor integration, Visual Perception, and Motor Coordination. Our data suggests that 3q29del may qualify as a nonverbal learning disability. Future studies should assess whether individuals with 3q29del would benefit from early interventions, including occupational therapy.

Contemporary Outcomes in Fetuses Diagnosed with Vascular Rings.

Vascular rings are increasingly identified on fetal echocardiography. The purpose of this study is to analyze clinical outcomes and patterns of diagnostic testing in fetuses with vascular rings diagnosed by echocardiography. A retrospective cohort study was performed of fetuses with postnatally confirmed vascular rings from 2017 to 2022. Clinical outcomes included type and timing of symptoms, and timing of surgical intervention. Freedom from symptoms and/or surgery was assessed by Kaplan-Meier analysis. Frequency of genetic and diagnostic testing (barium esophagogram, CT/MRI angiogram, and bronchoscopy) was also assessed. Overall, 46 patients were evaluated (91% with a right aortic arch/left ductus and 4% with a double aortic arch). A vascular ring was isolated in 59%, associated with structural heart lesions in 33%, and associated with noncardiac anomalies in 8%. Prenatal diagnoses increased over time. Symptoms developed in 24% (11/46); 82% (9/11) had respiratory and 45% (5/11) had gastroesophageal complaints. Surgery was performed in 17% (11/46). Symptoms presented bimodally, prior to 100 or after 400days of life. There was no difference in the type of symptoms for early (< 100days) or late (> 400days) presenters. Symptomatic patients received more diagnostic testing. Genetic testing was obtained in 46% and positive in 33%, with 22q11 deletion and Trisomy 21 being identified. Prenatal diagnoses of vascular rings increased over time, with subjects developing symptoms bimodally in early or late infancy. The frequency of genetic testing was suboptimal given the prevalence of genetic abnormalities seen in this population.

Purtscher-like retinopathy in a 19-year-old with maturity-onset diabetes of the young: a case report

BackgroundWe report the first case of Purtscher-like retinopathy in a patient with 17q12 deletion-associated maturity-onset diabetes of the young.Case presentationA 19-year-old diabetic Hispanic male with history of cataracts and toe amputations presented with sudden onset of painless bilateral vision loss for 1 week with no associated trauma. Visual acuity was counting fingers at six feet in both eyes. Dilated retinal examination revealed bilateral peripapillary cotton wool spots and intraretinal hemorrhages, and significant subretinal and intraretinal fluid on optical coherence tomography. Fluorescein angiography revealed arteriolar staining and leakage around the disc with areas of capillary nonperfusion, supporting the diagnosis of Purtscher-like retinopathy. Systemic workup revealed multiple diabetic complications including chronic osteomyelitis of multiple toes, nonhealing diabetic foot ulcers, neurogenic bladder and bowel, and bilateral lower-extremity muscular neuropathies. Genetic evaluation revealed a 17q12 deletion, which is associated with maturity-onset diabetes of the young 5. On follow-up examination, he received a single intravitreal antivascular endothelial growth factor injection in the left eye (off label) for persistent macular edema. Although his retinal edema improved, his visual acuity remained poor.ConclusionsThe presentation of our patient’s multiple diabetic complications along visual symptoms suggests Purtscher-like retinopathy can be a sequela of uncontrolled diabetes. Purtscher-like retinopathy is a rare but possible consideration in diabetic patients who present with acute-onset vision loss.