OBJECTIVE: To explore the role of multidisciplinary velopharyngeal dysfunction (VPD) assessment in diagnosing 22q11.2 deletion syndrome (22q) in children.
METHODS: Retrospective cohort study.
METHODS: Multidisciplinary VPD clinic at a tertiary pediatric hospital.
METHODS: Seventy-five children with genetically confirmed 22q evaluated at the VPD clinic between February 2007 and February 2023, including both previously diagnosed patients and those newly diagnosed as a result of VPD evaluation.
METHODS: Comprehensive review of medical records, utilizing ICD-10 codes and an institutional tool for keyword searches, to identify patients and collect data on clinical variables and outcomes.
METHODS: Characteristics of children with 22q, pathways to diagnosis, and clinical presentations that led to genetic testing for 22q.
RESULTS: Of the 75 children, 9 were newly diagnosed with 22q following VPD evaluation. Non-cleft VPI was a significant indicator for 22q in children not previously diagnosed, occurring in 100% of newly diagnosed cases compared to 52% of cases with existing 22q diagnosis (P = .008). Additional clinical findings leading to diagnosis included congenital heart disease, craniofacial abnormalities, and developmental delays.
CONCLUSIONS: VPD evaluations, particularly the presence of non-cleft VPI, play a crucial role in identifying undiagnosed cases of 22q. This underscores the need for clinicians, including plastic surgeons, otolaryngologists, and speech-language pathologists, to maintain a high degree of suspicion for 22q in children presenting with VPI without a clear etiology. Multidisciplinary approaches are essential for early diagnosis and management of this complex condition.

Congenital heart defects (CHDs) have had an increasing prevalence over the last decades, being one of the most common congenital defects. Their etiopathogenesis is multifactorial in origin. About 10-15% of all CHD can be attributed to copy number variations (CNVs), a type of submicroscopic structural genetic alterations. The aim of this study was to evaluate the involvement of CNVs in the development of congenital heart defects. We performed a cohort study investigating the presence of CNVs in the 22q11.2 region and GATA4, TBX5, NKX2-5, BMP4, and CRELD1 genes in patients with syndromic and isolated CHDs. A total of 56 patients were included in the study, half of them (28 subjects) being classified as syndromic. The most common heart defect in our study population was ventricular septal defect (VSD) at 39.28%. There were no statistically significant differences between the two groups in terms of CHD-type distribution, demographical, and clinical features, with the exceptions of birth length, weight, and length at the time of blood sampling, that were significantly lower in the syndromic group. Through multiplex ligation-dependent probe amplification (MLPA) analysis, we found two heterozygous deletions in the 22q11.2 region, both in patients from the syndromic group. No CNVs involving GATA4, NKX2-5, TBX5, BMP4, and CRELD1 genes were identified in our study. We conclude that the MLPA assay may be used as a first genetic test in patients with syndromic CHD and that the 22q11.2 region may be included in the panels used for screening these patients.

A frequently occurring genetic disorder, 22q11.2 deletion syndrome can manifest with various abnormalities. The range of cardiac anomalies associated with this syndrome is extensive, with conotruncal defects being the most prevalent. In this study, we report the case of a patient with a unique combination of anatomical abnormalities such as crisscross pulmonary arteries, a cervical aortic arch with coarctation of the aorta, and a ventricular septal defect. The patient underwent initial surgical intervention, which resulted in significant clinical improvement.

We present a case of an infant male born at 23 weeks\' gestation with an interrupted aortic arch (IAA) complex. We treated the patient with hypoxic gas ventilation to address developing systemic undercirculation in the acute postnatal phase. As the symptoms of bronchopulmonary dysplasia evolved, hypoxic gas ventilation was no longer required to stabilize the hemodynamics. The patient was discharged home after undergoing the palliative surgical procedure of bilateral pulmonary artery banding and ductus arteriosus stent implantation. Although he suffered from pulmonary hypertension, it was controllable with oxygen supplementation and pulmonary vasodilators. There are limited therapeutic options available for extremely preterm infants with critical congenital heart defects (CHDs). Hypoxic gas ventilation might be considered as one of the options, with its risks taken into account, to manage extremely preterm infants with CHDs with pulmonary overcirculation before performing surgical interventions.

Genomic disorders result from heterozygous copy number variants (CNVs). Homozygous deletions spanning numerous genes are rare, despite the potential contribution of consanguinity to such instances. CNVs in the 22q11.2 region are mediated by nonallelic homologous recombination between pairs of low copy repeats (LCRs), from amongst eight LCRs designated A-H. Heterozygous distal type II deletions (LCR-E to LCR-F) have incomplete penetrance and variable expressivity, and can lead to neurodevelopmental issues, minor craniofacial anomalies, and congenital abnormalities. We report siblings with global developmental delay, hypotonia, minor craniofacial anomalies, ocular abnormalities, and minor skeletal issues, in whom chromosomal microarray identified a homozygous distal type II deletion. The deletion was brought to homozygosity as a result of a consanguineous marriage between two heterozygous carriers of the deletion. The phenotype of the children was strikingly more severe and complex than that of the parents. This report suggests that the distal type II deletion harbors a dosage-sensitive gene or regulatory element, which leads to a more severe phenotype when deleted on both chromosomes.

To date, 22q11.2 deletion syndrome (DS) is regarded as the most commonly diagnosed DS in humans. The location of the deletion on chromosome 22 affects the phenotypic presentation, which ranges from subtle to severe. Common manifestations include congenital heart defects, calcium deficiency, clefts and other midline defects, immunodeficiencies, and neurocognitive delay. This wide range of clinical manifestations can complicate diagnostic reasoning as many align with other disease processes commonly observed in preterm neonates. This article presents the case of a preterm neonate born at 25-weeks\' gestation with 22q11.2 DS. The clinical presentation of this neonate included a right aortic arch, ventricular septal defect, hypocalcemia, borderline severe combined immunodeficiency, and abnormal thyroid function. The infant\'s hospital course is followed to highlight the challenges clinicians face when suspicious of a genetic disorder in a preterm neonate.

The 22q11.2 deletion syndrome is a multisystemic disorder characterized by a marked variability of phenotypic features, making the diagnosis challenging for clinicians. The wide spectrum of clinical manifestations includes congenital heart defects-most frequently conotruncal cardiac anomalies-thymic hypoplasia and predominating cellular immune deficiency, laryngeal developmental defects, midline anomalies with cleft palate and velar insufficiency, structural airway defects, facial dysmorphism, parathyroid and thyroid gland hormonal dysfunctions, speech delay, developmental delay, and neurocognitive and psychiatric disorders. Significant progress has been made in understanding the complex molecular genetic etiology of 22q11.2 deletion syndrome underpinning the heterogeneity of clinical manifestations. The deletion is caused by chromosomal rearrangements in meiosis and is mediated by non-allelic homologous recombination events between low copy repeats or segmental duplications in the 22q11.2 region. A range of genetic modifiers and environmental factors, as well as the impact of hemizygosity on the remaining allele, contribute to the intricate genotype-phenotype relationships. This comprehensive review has been aimed at highlighting the molecular genetic background of 22q11.2 deletion syndrome in correlation with a clinical multidisciplinary approach.

Investigate incidence and natural history of otologic and sinonasal disease associated with 22q11.2 deletion syndrome.
Case series.
Tertiary care children\'s hospital.
Charts from consecutive children born 2000 to 2018 with a diagnosis of 22q11.2 deletion, DiGeorge, or velocardiofacial syndrome based on the International Classification of Diseases (ICD)-9 and ICD-10 codes were reviewed. Otologic and rhinologic diagnoses and surgeries and immune and microbiologic laboratory findings were collected from the medical record.
After the exclusion of patients with no 22q11.2 deletion (n = 101), otologic care at an outside hospital (n = 59), and loss to follow-up prior to 3 years of age (n = 22), 128 were included. Males comprised 80 (62.5%) patients, 115 (89.8%) were white, and the median age at genetic confirmation of 22q11.2 deletion was 119 days (range 0 days to 14.6 years). Recurrent acute otitis media (RAOM), chronic otitis media with effusion, chronic rhinosinusitis, and recurrent acute sinusitis were diagnosed in 54 (42.2%), 37 (28.9%), 10 (7.8%), and 8 (6.3%), respectively. Tympanostomy tubes were placed in 49 (38.3%). Adenoidectomy and sinus surgery were performed in 38 (29.7%) and 4 (3.1%), respectively. Neither immunoglobulin nor cluster of differentiation deficiency increased the odds of RAOM diagnosis, tympanostomy tube placement, or chronic/recurrent sinusitis. Methicillin-resistant Staphylococcus aureus was the most common organism in sinus cultures (4/13, 30.8%). Streptococcus pneumonia dominated otorrhea cultures (11/21, 52.4%).
Approximately half of children with 22q11.2 deletion may experience otologic disease that often requires surgical management. Future studies will utilize a larger cohort to examine the role of immunodeficiency in otologic and rhinologic disease in this population.

The thymus gland plays a crucial role in the maturation process of lymphocyte T cells. Developmental disorders of this organ might be caused by genetic diseases, such as the 22q11.2 deletion and DiGeorge syndrome. Other manifestations of this condition are heart defects, a reduced number of T cells, hypocalcemia, and facial dysmorphia. A 13-year-old boy with 22q11 deletion syndrome presented with paresis and paresthesia of the right upper extremity. Magnetic resonance imaging (MRI) revealed a solid mass in the retropharyngeal and prevertebral areas. The lesion was excised and, upon histopathological examination, turned out to be ectopic thymic tissue. A follow-up examination showed no recurrence of the lesion. The ectopic thymus is a rare pathology, especially in 22q11 deletion syndrome patients. In general, thymic tissue can be found anywhere along its normal path of descent. In this case, however, its location cannot be explained solely by its embryological origin, as at no point should the thymus or its histological predecessor be located in the retropharyngeal area. As such, this finding challenges our current understanding of thymic embryological genesis.

Current practices vary widely regarding the immunological work-up and management of patients affected with defects in thymic development (DTD), which include chromosome 22q11.2 microdeletion syndrome (22q11.2del) and other causes of DiGeorge syndrome (DGS) and coloboma, heart defect, atresia choanae, retardation of growth and development, genital hypoplasia, ear anomalies/deafness (CHARGE) syndrome. Practice variations affect the initial and subsequent assessment of immune function, the terminology used to describe the condition and immune status, the accepted criteria for recommending live vaccines, and how often follow-up is needed based on the degree of immune compromise. The lack of consensus and widely varying practices highlight the need to establish updated immunological clinical practice guidelines. These guideline recommendations provide a comprehensive review for immunologists and other clinicians who manage immune aspects of this group of disorders.