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

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Emerging findings for the assessment and treatment of pediatric deep neck abscesses.

PURPOSE OF REVIEW: The purpose of this review is to summarize new literature regarding the description, diagnosis, and treatment of pediatric deep neck abscesses. RECENT FINDINGS: Providers should include multi-inflammatory syndrome in children (MIS-C) in a differential diagnosis in children suspected of having a retropharyngeal abscess. MRI may guide the proper management of children with deep neck abscesses by more accurately detecting free fluid compared to computed tomography imaging. Factors that may predict the need for surgical management include elevations in white blood cell counts and abscess size more than 3 cm. However, future investigation is necessary to establish consistent guidelines. Medical management is effective in many children, with a new study indicating success using a combination of cefotaxime and rifampicin. SUMMARY: Anatomical and age-related risk factors predispose children to the development of deep neck abscesses. Findings from recent studies may aid providers in making an accurate diagnosis and providing proper medical or surgical management of children with these infections.

Oropharyngeal Teratoma: Five-Month-Old Presenting With Failure to Thrive and Severe Obstructive Sleep Apnea.

Oropharyngeal teratomas are an extremely rare congenital tumor. They are often diagnosed prenatally and can cause significant airway obstruction and feeding difficulties at birth. We present a five-month-old female that was diagnosed with a palatal teratoma that presented with failure to thrive, difficulty feeding, and eventually with severe obstructive sleep apnea. We present a five-month-old term, otherwise healthy female who became stridulous after an episode of the respiratory syncytial virus at one month old. At three months old, an otolaryngologist diagnosed mild laryngomalacia with no mass identified, and no surgical intervention was recommended. Due to continued poor weight gain, at four months old, a nasogastric tube was placed. She was subsequently admitted for further workup. She had severe stridor, a failure to thrive, and was in the 0.07th percentile for weight. Workup revealed severe obstructive sleep apnea and a palatal mass obstructing her left oropharynx. A biopsy and debulking of the mass was performed in the operating room. Pathology resulted as a mature teratoma with evidence of glial and intestinal tissue. There are no pathognomonic characteristics found on imaging to diagnose teratomas, and diagnosis is made with pathologic identification of two of the three germ cell layers. Although most teratomas are benign, there is potential for malignant transformation involving any of the represented germ cell layers. Many teratomas are diagnosed prenatally and can be quite large, often requiring Ex Utero Intrapartum Treatment (EXIT) procedure at birth to establish a safe airway. Overall, this case highlights the importance of a thorough head and neck exam, including a bilateral flexible laryngoscopy, when evaluating an infant with airway obstruction. Providers evaluating these patients should consider oropharyngeal masses, such as teratoma, as part of the differential to ensure accurate and timely diagnosis.

Pediatric COVID-19 Involving Complicated Sinusitis With Intracranial Extension and Lemierre Syndrome: A Case Report.

Pediatric coronavirus disease 2019 (COVID-19) has been associated with various complications including chronic respiratory disease and multisystem inflammatory syndrome. There are a few reported cases of complicated sinusitis following pediatric COVID-19 infection. We present a patient with recent COVID-19 who developed complicated sinusitis with intracranial extension and Lemierre syndrome. A 16-year-old female with a history of COVID-19 diagnosis 17 days prior presented with worsening head and neck symptoms. Physical examination demonstrated left proptosis, cranial nerve (CN) VI palsy, and limited neck range of motion. Imaging demonstrated bilateral sinus disease, a 3.3 × 2 × 3-centimeter sellar/clival abscess, bilateral cavernous sinus thrombosis, and thrombosis of bilateral internal jugular veins. Urgent endoscopic sinus surgery was performed, and long-term intravenous antibiotics and anticoagulation were initiated with improvement in symptoms over three weeks. Providers caring for patients with COVID-19 should keep complicated sinusitis and Lemierre syndrome in their differential. Further study of COVID-19 pathophysiology in the sinonasal mucosa is needed.

Updated clinical practice recommendations for managing adults with 22q11.2 deletion syndrome.

This review aimed to update the clinical practice guidelines for managing adults with 22q11.2 deletion syndrome (22q11.2DS). The 22q11.2 Society recruited expert clinicians worldwide to revise the original clinical practice guidelines for adults in a stepwise process according to best practices: (1) a systematic literature search (1992-2021), (2) study selection and synthesis by clinical experts from 8 countries, covering 24 subspecialties, and (3) formulation of consensus recommendations based on the literature and further shaped by patient advocate survey results. Of 2441 22q11.2DS-relevant publications initially identified, 2344 received full-text review, with 2318 meeting inclusion criteria (clinical care relevance to 22q11.2DS) including 894 with potential relevance to adults. The evidence base remains limited. Thus multidisciplinary recommendations represent statements of current best practice for this evolving field, informed by the available literature. These recommendations provide guidance for the recognition, evaluation, surveillance, and management of the many emerging and chronic 22q11.2DS-associated multisystem morbidities relevant to adults. The recommendations also address key genetic counseling and psychosocial considerations for the increasing numbers of adults with this complex condition.

Updated clinical practice recommendations for managing children with 22q11.2 deletion syndrome.

This review aimed to update the clinical practice guidelines for managing children and adolescents with 22q11.2 deletion syndrome (22q11.2DS). The 22q11.2 Society, the international scientific organization studying chromosome 22q11.2 differences and related conditions, recruited expert clinicians worldwide to revise the original 2011 pediatric clinical practice guidelines in a stepwise process: (1) a systematic literature search (1992-2021), (2) study selection and data extraction by clinical experts from 9 different countries, covering 24 subspecialties, and (3) creation of a draft consensus document based on the literature and expert opinion, which was further shaped by survey results from family support organizations regarding perceived needs. Of 2441 22q11.2DS-relevant publications initially identified, 2344 received full-text reviews, including 1545 meeting criteria for potential relevance to clinical care of children and adolescents. Informed by the available literature, recommendations were formulated. Given evidence base limitations, multidisciplinary recommendations represent consensus statements of good practice for this evolving field. These recommendations provide contemporary guidance for evaluation, surveillance, and management of the many 22q11.2DS-associated physical, cognitive, behavioral, and psychiatric morbidities while addressing important genetic counseling and psychosocial issues.

Sleep profiles in children with 22q deletion syndrome: a study of 100 consecutive children seen in a multidisciplinary clinic.

STUDY OBJECTIVES: While previous studies have suggested a high prevalence of sleep disorders in children with 22q deletion syndrome (22qDS), they were limited by potential selection bias. In the current investigation, we assessed sleep characteristics in 100 consecutive children presenting to a 22qDS multidisciplinary clinic. METHODS: An observational retrospective case series of consecutive children presenting to 22qDS multidisciplinary clinic was performed. Children aged 2 to 17 years of age were included, and data were abstracted including sleep characteristics (sleep history, Childhood Sleep Habits Questionnaire [CSHQ], and free response questions), comorbid medical conditions, and demographics. RESULTS: Overall, 100 children were included in analysis, 85% of whom had scores on the CSHQ consistent with clinically meaningful sleep disorder. Sleep problems were common in all domains of the CSHQ, including daytime sleepiness (66%), sleep-onset delay (54%), parasomnias (52%), night wakings (52%), sleep-disordered breathing (49%), sleep duration (45%), bedtime resistance (38%), and sleep anxiety (33%). Overall CSHQ score was significantly associated with daytime behavioral problems and speech delay [F(2,97) = 10.4, P < .001, adjusted R2 = 0.16]. The most common interventions reported to be helpful for sleep by parents were behavioral (routine, bedtime story), environmental (light avoidance at night, calming music), and pharmacologic (melatonin, clonidine). CONCLUSIONS: These data confirm a high prevalence of sleep disorders in a large, unselected sample of children with 22qDS, and suggest an important relationship between sleep dysfunction and daytime behavioral challenges. Our findings highlight the potential role for multimodal treatment approaches including behavioral, environmental, and pharmacologic interventions. CITATION: Ingram DG, Raje N, Arganbright JM. Sleep profiles in children with 22q deletion syndrome: a study of 100 consecutive children seen in a multidisciplinary clinic. J Clin Sleep Med. 2023;19(1):27-34.

Tonsillectomy in Children with 22q11.2 Deletion Syndrome.

Tonsillectomy is one of the most common procedures performed in children, however there are currently no published studies evaluating tonsillectomy in children with 22q11.2 deletion syndrome (22q11DS). With this study, our goal was to investigate the indications, efficacy, and complications of tonsillectomy in a pediatric cohort of patients with 22q11DS. This is a retrospective chart review of patients in our 22q Center's repository. Inclusion criteria were a diagnosis of 22q11DS and a history of tonsillectomy or adenotonsillectomy. Data collected included: indications for tonsillectomy, preoperative and postoperative polysomnography (PSG) results, and surgical complications. In total, 33 patients were included. Most common indications for tonsillectomy were facilitation with speech surgery (n = 21) and sleep-disordered breathing (SDB)/obstructive sleep apnea (OSA) (n = 16). Average length of stay was 1.15 days. Most patients (69%) had some degree of persistent OSA on postoperative PSG. Complications occurred in 18% of patients and included respiratory distress, hemorrhage, and hypocalcemia. This study demonstrates tonsillectomy was a commonly performed procedure in this cohort of patients with 22q11DS. These data highlight the potential need for close postoperative calcium and respiratory monitoring. The data were limited with respect to PSG outcomes, and future studies are needed to better characterize OSA outcomes and complications in this patient population.

Airway anomalies in patients with 22q11.2 deletion syndrome: A scoping review.

OBJECTIVE: People with 22q11.2 deletion syndrome (22q11DS) can present with a wide variety of findings. Various airway anomalies have been described intermittently within this syndrome, but this feature has not been extensively investigated. Increased provider awareness of these findings may help guide clinical decision-making and improve overall patient outcomes. The objectives of this review are to identify the types of airway anomalies in 22q11DS and the prevalence of airway anomalies within symptomatic individuals. METHODS: PubMed/MEDLINE, Cochrane Library, and EMBASE databases were searched in February 2022 for all available articles. Search terms included those that described 22q11DS or one of its synonymous conditions AND those that described airway anatomy and anomalies. The term airway anomaly was defined as any structural aberration in the conductive airway from the oral or nasal vestibule region to the mainstem bronchus. Studies were screened by two authors. A review of references was conducted. Eligible manuscripts underwent full-text review for quality appraisal and data extraction. RESULTS: From a total of 909 unique manuscripts, 58 studies were selected, describing 328 people. The prevalence of airway anomaly diagnosis within symptomatic individuals ranged from 14% to 74%. Twenty-two unique airway anomalies were described. Laryngeal web was the most frequently described anomaly, followed by airway malacia and subglottic stenosis. Laryngeal web was 40% sensitive for suggesting a diagnosis of 22q11DS. Among affected individuals, as many as 46% had multiple concomitant airway anomalies. Aside from respiratory symptoms, other features that prompted airway evaluation included difficult intubation or failed extubation. CONCLUSION: The findings within this review support the notion that a wide variety of airway anomalies may be seen in people with 22q11DS and that these findings have been discovered frequently in those with airway symptoms. Providers should maintain a low threshold to perform an airway examination in those with 22q11DS, especially when airway symptoms are present.

Sleep Disorders in Children with Prader Willi Syndrome: Current Perspectives.

Children with Prader-Willi syndrome (PWS) face a multitude of potential health challenges including life-threatening obesity, endocrinopathies, behavioral and emotional dysregulation, developmental delays, and sleep disorders. In the current perspective piece, we provide a focused review of the condition's etiology and clinical findings, as well as a more in-depth discussion of sleep disorders frequently associated with PWS. In particular, we highlight and discuss difficult clinical scenarios frequently encountered by the pediatric sleep physician caring for this patient population, including diagnosis and treatment of complex sleep-related breathing disorders, considerations for sleep apnea surgery, the interplay between growth hormone and sleep apnea, diagnostic challenges in hypersomnia/narcolepsy, and current and emerging therapies for hypersomnia/narcolepsy. Overall, although there are many areas that need further research, sleep disorders remain a fruitful target for improving quality of life of children with PWS and their families.

Postoperative Hypocalcemia following Non-Cardiac Surgical Procedures in Children with 22q11.2 Deletion Syndrome.

The guidelines for management of children with 22q11.2 deletion syndrome (22q11DS) highlight the risk for developing hypocalcemia after surgery and recommend monitoring calcium perioperatively. Despite this guidance, little has been published on postoperative hypocalcemia and 22q11DS. Our goals were to evaluate the frequency of perioperative calcium monitoring and examine how often postoperative hypocalcemia was identified. This is a retrospective chart review of patients in our 22q Center's repository. Inclusion criteria were a diagnosis of 22q11DS and a history of a non-cardiac surgical procedure. Data collected included all non-cardiac surgeries and perioperative calcium labs. In total, 68 patients were included and underwent 305 on-cardiac surgeries. Patients in only 17% of these surgeries had postoperative calcium testing, but of those tested, 58% showed hypocalcemia. Patients with history of hypocalcemia at the time of chart review undergoing non-cardiac surgeries were tested postoperatively 40% of the time; however, 67% of these had hypocalcemia. Similarly, for patients without history of hypocalcemia, postoperative testing occurred 60% of the time, with 52% of these having hypocalcemia. This study demonstrates that postoperative hypocalcemia in children with 22q11DS following non-cardiac surgeries is common and affects patients both with and without prior history of hypocalcemia. These data support establishing a protocol for perioperative testing/management of hypocalcemia for patients with 22q11DS.

22q11.2 duplications: Expanding the clinical presentation.

22q11.2 duplication syndrome has a frequency of ~1/700 in the intellectual disability population. Despite this frequency, there is limited information on the variable clinical presentation. Although the phenotype and incidence of congenital anomalies are well described for 22q11.2 deletion syndrome, they are not as well understood for individuals with 22q11.2 duplication syndrome. This study is a single-center, retrospective review of patients diagnosed with 22q11.2 duplication syndrome designed to categorize the variable phenotype seen in these individuals. The data suggest that the incidence of congenital anomalies may be higher than previously reported for this syndrome. Affected individuals are at increased risk for a variety of problems including gastrointestinal complications, endocrine dysfunction, ophthalmologic abnormalities, palatal anomalies, congenital heart disease, musculoskeletal differences, and neurologic abnormalities. Individuals with 22q11.2 duplication syndrome would benefit from care coordinated by a multidisciplinary team and managed according to the 22q11.2 deletion syndrome guidelines.

Microsurgical Management of Early Onset Alveolar Soft Part Sarcoma of the Oral Tongue: Case Report and Review of the Literature.

OBJECTIVES: Alveolar soft part sarcoma is a rare subset of soft tissue sarcomas, typically presenting in subjects 15 to 35 years of age. Usual presentation sites are the trunk, extremities, and the head and neck. Subjects younger than 5 years are rarely affected. METHODS: In this retrospective case report, we present a 16-month old male with a rapidly growing soft tissue mass of the anterior and posterior tongue, found to be alveolar soft part sarcoma. RESULTS: The subject was treated with primary surgical resection and the resulting defect was reconstructed with a radial forearm free flap. CONCLUSIONS: To our knowledge, this is the youngest subject to have been diagnosed with alveolar soft part sarcoma. Surgical extirpation and microvascular reconstruction were successful, and the patient remains disease free 4 years post-operatively.

Pediatric drug-induced sleep endoscopy: An updated review of the literature.

The field of drug-induced sleep endoscopy (DISE) has grown considerably over the last 10∼15 years, to now include its use in pediatric patients. In this review article, we outline our approach to the use of this technology in Children with Airway Obstruction, most specifically in the management of children with airway obstruction and known or suspected adenotonsillar enlargement.

Sleep patterns and problems among children with 22q11 deletion syndrome.

BACKGROUND: To delineate sleep habits and problems in children with 22q11.2 deletion syndrome (22q11DS). METHODS: Thirty children, age 1-15 (mean 6.8) years, participated in the study, which was an internet-based anonymous survey of parents of children with 22q11DS administered via the 22q11.2 Foundation. The main outcome was the Childhood Sleep Habits Questionnaire (CSHQ). RESULTS: Scores on the CSHQ demonstrated clinically significant sleep problems in 29 of the 30 children. When compared with previously reported normative values for typically developing children of the same age, children with 22q11DS had significantly greater sleep problems. Only 30% of children had previously undergone sleep study. While about half of children had tried a medication for sleep, it usually was not felt to be helpful. In contrast, parents reported that behavioral interventions, such as consistent bedtime routine and appropriate sleep environment, were helpful. This is one of the first studies to specifically address sleep problems other than obstructive sleep apnea in children with 22q11DS. CONCLUSIONS: The findings suggest children with 22q11DS may have a higher risk of experiencing clinical sleep problems, compared to typically developing children. Consideration of additional screening and treatment of sleep disorders in children with 22q11DS is warranted.

The Generalizability of the Clinical Assessment Score-15 for Pediatric Sleep-Disordered Breathing.

OBJECTIVE: The Clinical Assessment Score-15 (CAS-15) has been validated as an office-based assessment for pediatric sleep-disordered breathing in otherwise healthy children. Our objective was to determine the generalizability of the CAS-15 in a multi-institutional fashion. METHODS: Five hundred and thirty children from 13 sites with suspected sleep-disordered breathing were recruited, and the investigators completed the CAS-15. Based on decisions made in the course of clinical care, investigators recommended overnight polysomnography, observation, medical therapy, and/or surgery. Two hundred and forty-seven subjects had a follow-up CAS-15. RESULTS: Mean age was 5.1 (2.6) years; 54.2% were male; 39.1% were white; and 37.0% were African American. Initial mean (standard deviation [SD]) CAS-15 was 37.3 (12.7), n = 508. Spearman correlation between the initial CAS-15 and the initial apnea-hypopnea index (AHI) was 0.41 (95% confidence interval [CI], 0.29, 0.51), n = 212, P < .001. A receiver-operating characteristic curve predicting positive polysomnography (AHI > 2) had an area under the curve of 0.71 (95% CI, 0.63, 0.80). A score ≥ 32 had a sensitivity of 69.0% (95% CI, 61.7, 75.5), a specificity of 63.4% (95% CI, 47.9, 76.6), a positive predictive value of 88.7% (95% CI, 82.1, 93.1), and a negative predictive value of 32.9% (95% CI, 23.5, 44.0) in predicting positive polysomnography. Among children who underwent surgery, the mean change (SD) score was 30.5 (12.6), n = 201, t = 36.85, P < .001, effect size = 3.1. CONCLUSION: This study establishes the generalizability of the CAS-15 as a useful office tool for the evaluation of pediatric sleep-disordered breathing. LEVEL OF EVIDENCE: 2B Laryngoscope, 130:2256-2262, 2020.

Airway Anomalies in Patients With 22q11.2 Deletion Syndrome: A 5-Year Review.

OBJECTIVES: To characterize the frequency of airway anomalies in patients with 22q11.2 deletion syndrome (22q11DS). METHODS: Retrospective review of patients with 22q11DS who had undergone microlaryngoscopy/bronchoscopy (MLB) for aerodigestive symptoms at a tertiary care children's hospital from 2011 to 2016. RESULTS: Thirty patients underwent an MLB due to the following indications: aspiration (11), stridor (10), chronic respiratory failure due to ventilator dependence (8), and difficult intubation (1). Median age at MLB was 6.5 months (range, 0.25-32 months). Forty airway anomalies were identified in 20 (66%) patients. Laryngomalacia (10), tracheomalacia (8), and bronchomalcia (8) were the most common intraoperative findings, followed by laryngeal cleft (5), anterior glottic web (5), subglottic stenosis (3), and subglottic cysts (1). Synchronous airway anomalies were common and identified in 11 (55%) of the patients who had identified anomalies on MLB. Nineteen of the 20 patients required operative intervention due to the anomalies identified. CONCLUSIONS: Structural airway abnormalities are common in children with 22q11DS undergoing MLB, and synchronous anomalies can frequently exist. Providers caring for children with 22q11DS should be vigilant about airway evaluation when aerodigestive symptoms are present.

Revisiting the argument for 1- versus 2-vein outflow in head and neck free tissue transfers: A review of 317 microvascular reconstructions.

BACKGROUND: The purpose of this study was to determine the benefit of 1-vein versus 2-vein outflow in microvascular free tissue transfers. METHODS: A retrospective review reflects the experience of 6 surgeons. Analysis included all patients who underwent reconstruction at a single institution between January 2004 and December 2012. RESULTS: Three hundred nine patients underwent a total of 317 microvascular free flap reconstructions for head and neck defects. Two hundred thirteen of 317 flaps (67.2%) used 1 venous anastomosis and 104 (32.8%) used 2 venous anastomoses. Venous congestion necessitated urgent take back in 37 of 57 patients (64.9%) requiring exploration for perioperative complications. Thirty of 37 flaps (81.1%) with venous congestion had 1 vein anastomosis, whereas 7 (18.9%) had dual vein outflow (p = .03). Overall flap success was 303 of 317 (95.6%), despite an 18.0% (57 of 317) perioperative take back rate. CONCLUSION: Coapting 2 veins was shown to minimize venous congestion. © 2015 Wiley Periodicals, Inc. Head Neck 38: 820-823, 2016.

Evaluation of bone length and number of osteotomies utilizing the osteocutaneous radial forearm free flap for mandible reconstruction: An 8-year review of complications and flap survival.

BACKGROUND: The purpose of this study was to assess the impact of bone harvest length and multiple osteotomies on osteocutaneous radial forearm free flap (RFFF) complication rates. METHODS: A retrospective chart review was conducted for patients undergoing osteocutaneous RFFF reconstruction during an 8-year period. RESULTS: One hundred fifty-five osteocutaneous RFFF procedures were performed. Recipient-site flap complications were 18 of 55 (32.7%) when bone harvest length was less than 7 cm and 40 of 100 (40.0%) when it was ≥7 cm. No osteotomies were performed in 69 of 155 cases with a corresponding complication rate of 30.4% (21 of 69). One osteotomy was utilized in 69 of 155 flaps, whereas 17 of 155 required more than 1 osteotomy; complications were experienced in 42% (29 of 69) and 47% (8 of 17) of these cases, respectively. CONCLUSION: Osteocutaneous RFFF complication rates were only slightly higher when the bone length was ≥7 cm or when multiple osteotomies were required.