Sleep Disturbances in 22q11.2 Deletion Syndrome: A Case with Obstructive and Central Sleep Apnea

2007 ◽  
Vol 44 (3) ◽  
pp. 340-346 ◽  
Author(s):  
Carrie L. Heike ◽  
Anthony M. Avellino ◽  
Sohail K. Mirza ◽  
Yemiserach Kifle ◽  
Jonathan Perkins ◽  
...  
Keyword(s):  
Sleep Apnea ◽  
Sleep Disturbances ◽  
Phenotypic Variability ◽  
Central Sleep Apnea ◽  
22Q11.2 Deletion Syndrome ◽  
Obtuse Angle ◽  
Deletion Syndrome ◽  
22Q11.2 Deletion ◽  
Mandibular Distraction Osteogenesis ◽  
Obstructive Sleep

The 22q11.2 deletion syndrome is characterized by wide phenotypic variability, frequently involving characteristic craniofacial features, cardiac malformations, and learning difficulties. Skeletal anomalies are also common and include an obtuse angle of the cranial base, retrognathia, and cervical spine abnormalities. Despite these anomalies, sleep-disturbed breathing is not reported frequently in patients with 22q11.2 deletion syndrome. We describe a patient with an obstructive sleep disturbance that was successfully treated with a tonsillectomy followed by mandibular distraction osteogenesis. She also had central sleep apnea, initially attributed to spinal cord impingement from cervical instability. Posterior cervical fusion was associated with a decrease in the number of central apneic events.

22q11.2 Deletion syndrome and obstructive sleep apnea

2014 ◽  
Vol 78 (8) ◽  
pp. 1360-1364 ◽  
Author(s):  
William P. Kennedy ◽  
Pamela A. Mudd ◽  
Meg A. Maguire ◽  
Margaret C. Souders ◽  
Donna M. McDonald-McGinn ◽  
...  
Keyword(s):  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
22Q11.2 Deletion Syndrome ◽  
Deletion Syndrome ◽  
22Q11.2 Deletion ◽  
Obstructive Sleep

Surgical Management of Patients With 22q11.2 Deletion Syndrome

2019 ◽  
Vol 4 (5) ◽  
pp. 857-869
Author(s):  
Oksana A. Jackson ◽  
Alison E. Kaye
Keyword(s):  
Surgical Management ◽  
Preoperative Evaluation ◽  
Preoperative Assessment ◽  
22Q11.2 Deletion Syndrome ◽  
Deletion Syndrome ◽  
22Q11.2 Deletion ◽  
Surgical Decision ◽  
Obstructive Sleep ◽  
Spine Abnormalities ◽  
Speech Assessment

Purpose The purpose of this tutorial was to describe the surgical management of palate-related abnormalities associated with 22q11.2 deletion syndrome. Craniofacial differences in 22q11.2 deletion syndrome may include overt or occult clefting of the palate and/or lip along with oropharyngeal variances that may lead to velopharyngeal dysfunction. This chapter will describe these circumstances, including incidence, diagnosis, and indications for surgical intervention. Speech assessment and imaging of the velopharyngeal system will be discussed as it relates to preoperative evaluation and surgical decision making. Important for patients with 22q11.2 deletion syndrome is appropriate preoperative screening to assess for internal carotid artery positioning, cervical spine abnormalities, and obstructive sleep apnea. Timing of surgery as well as different techniques, common complications, and outcomes will also be discussed. Conclusion Management of velopharyngeal dysfunction in patients with 22q11.2 deletion syndrome is challenging and requires thoughtful preoperative assessment and planning as well as a careful surgical technique.

Defining Risk of Postoperative Obstructive Sleep Apnea in Patients With 22q11.2DS Undergoing Pharyngeal Flap Surgery for Velopharyngeal Dysfunction Using Polysomnographic Evaluation

2020 ◽  
Vol 57 (7) ◽  
pp. 808-818
Author(s):  
Alfred Lee ◽  
Brian L. Chang ◽  
Cynthia Solot ◽  
Terrence B. Crowley ◽  
Vamsee Vemulapalli ◽  
...  
Keyword(s):  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Tertiary Care ◽  
22Q11.2 Deletion Syndrome ◽  
Deletion Syndrome ◽  
Apnea Hypopnea Index ◽  
Pressure Therapy ◽  
Obstructive Sleep ◽  
Increased Risk ◽  
Pharyngeal Flap

Objective: To determine pre- and postoperative prevalence of obstructive sleep apnea (OSA) in patients with 22q11.2 deletion syndrome (DS) undergoing wide posterior pharyngeal flap (PPF) surgery for velopharyngeal dysfunction (VPD). Design: Retrospective study using pre- and postoperative polysomnography (PSG) to determine prevalence of OSA. Medical records were reviewed for patients’ medical comorbidities. Parents were surveyed about snoring. Setting: Academic tertiary care pediatric hospital. Patients: Forty patients with laboratory confirmed 22q11.2DS followed over a 6-year period. Interventions: Pre- and postoperative PSG, speech evaluation, and parent surveys. Main Outcome Measure: Severity and prevalence of OSA, defined by obstructive apnea hypopnea index (OAHI), before and after PPF surgery to determine whether PPF is associated with increased risk of OSA. Results: Mean OAHI did not change significantly after PPF surgery (1.1/h vs 2.1/h, P = .330). Prevalence of clinically significant OSA (OAHI ≥ 5) was identical pre- and postoperatively (2 of 40), with both cases having severe-range OSA requiring positive airway pressure therapy. All other patients had mild-range OSA. Nasal resonance was graded as severe preoperatively in 85% of patients. None were graded as severe postoperatively. No single patient factor or parent-reported concern predicted risk of OSA (OAHI ≥ 1.5). Conclusions: Patients with 22q11.2DS are medically complex and are at increased risk of OSA at baseline. Wide PPF surgery for severe VPD does not significantly increase risk of OSA. Careful perioperative planning is essential to optimize both speech and sleep outcomes.

Polysomnography in Pediatric Otolaryngology: If Not Obstructive Sleep Apnea, What Is It?

2017 ◽  
Vol 157 (6) ◽  
pp. 1053-1059 ◽  
Author(s):  
Christine H. Heubi ◽  
Jareen Meinzen-Derr ◽  
Sally R. Shott ◽  
David F. Smith ◽  
and Stacey L. Ishman
Keyword(s):  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Sleep Disturbances ◽  
Case Series ◽  
Central Sleep Apnea ◽  
Categorical Variables ◽  
Periodic Limb Movements ◽  
Continuous Variables ◽  
Retrospective Case ◽  
Obstructive Sleep

Objective To determine common polysomnographic (PSG) diagnoses for children referred by otolaryngologists. Study Design Retrospective case series with chart review. Setting Single tertiary pediatric hospital (2010-2015). Subjects and Methods Review of the medical records of 1258 patients undergoing PSG by otolaryngology referral. Patients who underwent previous otolaryngologic surgery were excluded. Data distributions were evaluated using means with standard deviations for continuous variables and frequencies with percentages for categorical variables. Results A total of 1258 patients were included; 55.9% were male, 64.5% were Caucasian, 16.6% had Down syndrome, and 48% had public insurance. The median age at the time of PSG was 5.2 years (range = 0.2-18.94). Indications for PSG were sleep-disordered breathing (SDB; 69.4%), restless sleep (12.7%), airway anomalies (7.5%), and laryngomalacia (7.2%). SDB was seen in 73.4%, obstructive sleep apnea (OSA) in 53.2%, OSA + central sleep apnea (CSA) in 4.5%, CSA in 0.9%, and non-OSA snoring in 15%. Other diagnoses included periodic limb movements of sleep (PLMS; 7.4%), hypoventilation (6.8%), and nonapneic hypoxemia (2.6%). SDB was more common in younger children and seen in 91.4% of children <12 months and in 69.2% of children ≥24 months, while non-OSA snoring was more common with increasing age (3.7% in children <12 months, 17.7% of children ≥24 months). PLMS were seen in 8.9% of children ≥24 months and in no children <12 months. Conclusion While OSA and snoring were the most common diagnoses reported, PLMS, alveolar hypoventilation, and CSA occurred in 7.4%, 6.8%, and 5.4%, respectively. These findings indicate that additional diagnoses other than OSA should be considered for children seen in an otolaryngology clinic setting who undergo PSG for sleep disturbances.

scholarly journals 22q11.2 Low Copy Repeats Expanded in the Human Lineage

2021 ◽  
Vol 12 ◽  
Author(s):  
Lisanne Vervoort ◽  
Nicolas Dierckxsens ◽  
Zjef Pereboom ◽  
Oronzo Capozzi ◽  
Mariano Rocchi ◽  
...  
Keyword(s):  
Human Population ◽  
De Novo ◽  
Phenotypic Variability ◽  
22Q11.2 Deletion Syndrome ◽  
Deletion Syndrome ◽  
Species Variation ◽  
Human Lineage ◽  
22Q11.2 Deletion ◽  
Functional Studies ◽  
Low Copy Repeats

Segmental duplications or low copy repeats (LCRs) constitute duplicated regions interspersed in the human genome, currently neglected in standard analyses due to their extreme complexity. Recent functional studies have indicated the potential of genes within LCRs in synaptogenesis, neuronal migration, and neocortical expansion in the human lineage. One of the regions with the highest proportion of duplicated sequence is the 22q11.2 locus, carrying eight LCRs (LCR22-A until LCR22-H), and rearrangements between them cause the 22q11.2 deletion syndrome. The LCR22-A block was recently reported to be hypervariable in the human population. It remains unknown whether this variability also exists in non-human primates, since research is strongly hampered by the presence of sequence gaps in the human and non-human primate reference genomes. To chart the LCR22 haplotypes and the associated inter- and intra-species variability, we de novo assembled the region in non-human primates by a combination of optical mapping techniques. A minimal and likely ancient haplotype is present in the chimpanzee, bonobo, and rhesus monkey without intra-species variation. In addition, the optical maps identified assembly errors and closed gaps in the orthologous chromosome 22 reference sequences. These findings indicate the LCR22 expansion to be unique to the human population, which might indicate involvement of the region in human evolution and adaptation. Those maps will enable LCR22-specific functional studies and investigate potential associations with the phenotypic variability in the 22q11.2 deletion syndrome.

scholarly journals Ontogeny of the facial phenotypic variability in Mexican patients with 22q11.2 deletion syndrome

2019 ◽  
Vol 15 (1) ◽  
Author(s):  
Arodi Farrera ◽  
María Villanueva ◽  
Alfredo Vizcaíno ◽  
Patricia Medina-Bravo ◽  
Norma Balderrábano-Saucedo ◽  
...  
Keyword(s):  
Medical Condition ◽  
Phenotypic Variability ◽  
22Q11.2 Deletion Syndrome ◽  
Deletion Syndrome ◽  
Postnatal Ontogeny ◽  
Facial Morphology ◽  
22Q11.2 Deletion ◽  
Large Variability ◽  
Shape And Size ◽  
Mexican Patients

Abstract Background 22q11.2 deletion syndrome is a medical condition that results from genomic loss at chromosome 22. Affected patients exhibit large variability that ranges from a severe condition to mild symptoms. In addition, the spectrum of clinical features differs among populations and even within family members. The facial features related to this syndrome are not an exception, and although part of its variation arises through development, few studies address this topic in order to understand the intra and inter-population heterogeneities. Here, we analyze the ontogenetic dynamics of facial morphology of Mexican patients with del22q11.2 syndrome. Methods Frontal facial photographs of 37 patients (mean age = 7.65 ± 4.21 SE) with del22q11.2DS and 200 control subjects (mean age = 7.69 ± 4.26 SE) were analyzed using geometric morphometric methods. Overall mean shape and size differences between patients and controls were analyzed, as well as differences in ontogenetic trajectories (i.e. development, growth, and allometry). Results We found that Mexican patients show typical traits that have been reported for the Caucasian population. Additionally, there were significant differences between groups in the facial shape and size when all the ontogenetic stages were considered together and, along ontogeny. The developmental and allometric trajectories of patients and controls were similar, but they differed in allometric scaling. Finally, patients and controls showed different growth trajectories. Conclusion The results suggest that the typical face of patients with del22q11.2DS is established prenatally; nonetheless, the postnatal ontogeny could influence the dysmorphology and its variability through size-related changes.

Implications of COMT and Subclinical Psychiatric Symptoms on the Phenotypic Variability of 22q11.2 Deletion Syndrome: A Transversal and Longitudinal Approach

2017 ◽  
Vol 41 (S1) ◽  
pp. S82-S83
Author(s):  
S. Guerrera ◽  
M. Armando ◽  
M. Pontillo ◽  
F. Papaleo ◽  
S. Vicari
Keyword(s):  
Negative Symptoms ◽  
Psychiatric Symptoms ◽  
Phenotypic Variability ◽  
22Q11.2 Deletion Syndrome ◽  
Structured Interview ◽  
Deletion Syndrome ◽  
Psychotic Symptoms ◽  
22Q11.2 Deletion ◽  
Comt Polymorphism ◽  
The Impact

Introduction22q11.2 deletion syndrome (22q11.2DS) results from a hemizygous microdeletion on chromosome 22 and is characterized by phenotypic variability. Several studies have been conducted on the impact of COMT functional polymorphism in 22q11DS, suggesting that attenuated psychotic manifestations are frequent in children and adolescents and represent one of the strongest predictors for the onset of psychotic disorder.ObjectivesWe explored possible interaction between COMT polymorphism and subclinical psychiatric symptoms in a 22q11.2DS cohort of 42 participants aged 6 to 26 years: 17 hemizygosity for COMT-Met and 25 hemizygosity for COMT-Val.AimsTo analyse impact of COMT gene in 22q11DS and its related psychiatric correlates.MethodEach participant, genotyped for the catechol O-methyltransferase (COMT) Met/Val polymorphism, underwent structured psychiatric and cognitive assessment. Analysis of positive and negative symptoms was performed by the structured interview for prodromal syndromes (SIPS). Finally, longitudinal data available in a subsample of 24 individuals were used to explore the developmental trajectories of psychotic symptoms one year later.ResultsThere was a significant positive correlation between COMT Val polymorphism and positive symptoms; at follow-up, no significant correlation were found between COMT polymorphism and psychiatric symptoms. No other significant differences were found between groups (Comt/Met-Comt/Val) on any other CBCL or QI score.ConclusionsCOMT and additional genes microdeleted might interact in the susceptibility to schizophrenia in 22q11.2DS: psychotic symptoms might result from an epistatic interaction with other genes. Moreover, gene-environment, in presence of genetic vulnerability could increase the risk of schizophrenia in 22q11DS.Disclosure of interestThe authors have not supplied their declaration of competing interest.

scholarly journals Contribution of Mitochondrial DNA Heteroplasmy to the Congenital Cardiac and Palatal Phenotypic Variability in Maternally Transmitted 22q11.2 Deletion Syndrome

Genes ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 92
Author(s):  
Boris Rebolledo-Jaramillo ◽  
Maria Gabriela Obregon ◽  
Victoria Huckstadt ◽  
Abel Gomez ◽  
Gabriela M. Repetto
Keyword(s):  
Mitochondrial Dna ◽  
Permutation Test ◽  
Phenotypic Variability ◽  
22Q11.2 Deletion Syndrome ◽  
Deletion Syndrome ◽  
P Value ◽  
Incomplete Penetrance ◽  
Frequency Change ◽  
22Q11.2 Deletion ◽  
Mitochondrial Dna Heteroplasmy

Congenital heart disease (CHD) and palatal anomalies (PA), are among the most common characteristics of 22q11.2 deletion syndrome (22q11.2DS), but they show incomplete penetrance, suggesting the presence of additional factors. The 22q11.2 deleted region contains nuclear encoded mitochondrial genes, and since mitochondrial function is critical during development, we hypothesized that changes in the mitochondrial DNA (mtDNA) could be involved in the intrafamilial variability of CHD and PA in cases of maternally inherited 22q11.2DS. To investigate this, we studied the transmission of heteroplasmic mtDNA alleles in seventeen phenotypically concordant and discordant mother-offspring 22q11.2DS pairs. We sequenced their mtDNA and identified 26 heteroplasmic variants at >1% frequency, representing 18 transmissions. The median allele frequency change between a mother and her child was twice as much, with a wider distribution range, in PA discordant pairs, p-value = 0.039 (permutation test, 11 concordant vs. 7 discordant variants), but not in CHD discordant pairs, p-value = 0.441 (9 vs. 9). Only the variant m.9507T>C was considered to be pathogenic, but it was unrelated to the structural phenotypes. Our study is novel, yet our results are not consistent with mtDNA variation contributing to PA or CHD in 22q11.2DS. Larger cohorts and additional factors should be considered moving forward.

Sign in / Sign up

Export Citation Format

Share Document