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Correspondence and requests for materials should be addressed to Sólveig Óskarsdóttir, Department of Pediatric Rheumatology and Immunology, Queen Silvia Children’s Hospital, SE-416 85, Gothenburg, Sweden
Department of Pediatric Rheumatology and Immunology, Queen Silvia Children’s Hospital, Sahlgrenska University Hospital, Gothenburg, SwedenDepartment of Pediatrics, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
Advisium, ’s Heeren Loo Zorggroep, Amersfoort, The NetherlandsThe Dalglish Family 22q Clinic, University Health Network, Toronto, Ontario, CanadaDepartment of Psychiatry and Neuropsychology, Maastricht University, Maastricht, The Netherlands
Department of Psychiatry, Hospital for Sick Children, Toronto, Ontario, CanadaDepartment of Psychiatry, University of Toronto, Toronto, Ontario, CanadaGenetics & Genome Biology Program, Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada
Division of Neurology, 22q and You Center, Children’s Hospital of Philadelphia, Philadelphia, PADepartment of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA
Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PADivision of Pulmonary and Sleep Medicine, 22q and You Center, Children’s Hospital of Philadelphia, Philadelphia, PA
Department of Psychiatry and Neuropsychology, Maastricht University, Maastricht, The NetherlandsDepartment of Pediatric Psychology, University Medical Centre, Wilhelmina Children’s Hospital, Utrecht, The Netherlands
Division of Ophthalmology, The 22q and You Center, Children’s Hospital of Philadelphia, Philadelphia, PADepartment of Surgery, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA
Division of Neurology, 22q and You Center, Children’s Hospital of Philadelphia, Philadelphia, PADepartment of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA
Department of Surgery, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PACleft Lip and Palate Program, Division of Plastic, Reconstructive and Oral Surgery, 22q and You Center, Children’s Hospital of Philadelphia, Philadelphia, PA
Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PADivision of Endocrinology and Diabetes, 22q and You Center, Children’s Hospital of Philadelphia, Philadelphia, PA
Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PADivision of Hematology, 22q and You Center, Children’s Hospital of Philadelphia, Philadelphia, PA
Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PADivision of Gastroenterology, Hepatology and Nutrition, 22q and You Center, Children’s Hospital of Philadelphia, Philadelphia, PA
Richard D. Wood Jr. Center for Fetal Diagnosis and Treatment, 22q and You Center, The Children’s Hospital of Philadelphia, Philadelphia, PADepartments of Obstetrics and Gynecology and Surgery, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA
Rare Diseases Program, Institute for Sciences and Innovation in Medicine, Facultad de Medicina Clinica Alemana Universidad del Desarrollo, Santiago, Chile
Clinical Psychology Unit for Intellectual and Developmental Disabilities, Faculty of Psychology and Educational Sciences, University of Geneva, Geneva, Switzerland
Department of Speech-Language Pathology and Center for Childhood Communication, 22q and You Center, Children’s Hospital of Philadelphia, Philadelphia, PA
Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PADivision of Allergy and Immunology, 22q and You Center, The Children’s Hospital of Philadelphia, Philadelphia, PA
Pediatric Cardiology Unit, Department of Pediatrics, Obstetrics and Gynecology, “Sapienza” University of Rome, Rome, ItalyDepartment of Pediatric Cardiology and Cardiac Surgery, Ospedale Pediatrico Bambino Gesù, IRCCS, Rome, Italy
Department of Surgery, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PADivision of Urology, 22q and You Center, Children’s Hospital of Philadelphia, Philadelphia, PA
Advisium, ’s Heeren Loo Zorggroep, Amersfoort, The NetherlandsDepartment of Psychiatry and Neuropsychology, Maastricht University, Maastricht, The Netherlands
Department of Psychiatry, Hospital for Sick Children, Toronto, Ontario, CanadaGenetics & Genome Biology Program, Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada
Anne S. Bassett, The Dalglish Family 22q Clinic, University Health Network, 33 Ursula Franklin Street (formerly Russell St and Spadina), Toronto, Ontario M5S 2S1.
The Dalglish Family 22q Clinic, University Health Network, Toronto, Ontario, CanadaDepartment of Psychiatry, University of Toronto, Toronto, Ontario, CanadaGenetics & Genome Biology Program, Research Institute, Hospital for Sick Children, Toronto, Ontario, CanadaClinical Genetics Research Program and Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada
Donna M. McDonald-McGinn, Division of Human Genetics, 22q and You Center, Section of Genetic Counseling, and Clinical Genetics Center, Children’s Hospital of Philadelphia and Department of Pediatrics, Perelman School of Medicine of the University of Pennsylvania, 3500 Civic Center Blvd., Philadelphia, PA 19104.
The 22q and You Center, Clinical Genetics Center, and Division of Human Genetics, Children’s Hospital of Philadelphia, Philadelphia, PADepartment of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PADepartment of Human Biology and Medical Genetics, Sapienza University, Rome, Italy
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.
22q11.2 deletion is the most frequent cause of DiGeorge syndrome and several other conditions previously described clinically (velocardiofacial syndrome, conotruncal anomaly face syndrome, Cayler cardiofacial) and a subset of patients with Opitz G/BBB syndrome.
Figure 1Chromosome 22 ideogram and genes within the chromosome 22q11.2 LCR22A-LCR22D region. Cytogenetic representation of chromosome 22 showing the short (p) and long (q) arms along with the centromere, which functions to separate both arms. Chromosome 22 is an acrocentric chromosome, as indicated by the two horizontal lines in the p arm. The 22q11.2 deletion occurs on the long arm of 1 of the 2 chromosomes, depicted by dashed lines in the 22q11.2 band. The position of the 2 low copy repeats (LCRs), LCR22A and LCR22D, which flank the typical 3 Mb deletion, on 22q11.2 are indicated. Schematic representation of the 3 Mb chromosome 22q11.2 region that is commonly deleted in 22q11.2 deletion syndrome, including the 4 LCRs (LCR22s) that span this region (LCR22A, LCR22B, LCR22C, and LCR22D) and genes within the region. Common commercial probes for fluorescence in situ hybridization (FISH) are indicated (N25 and TUPLE). Protein-coding and selected noncoding (∗) genes are indicated with respect to their relative position along chromosome 22 (Chr22). T-box 1 (TBX1; green box) is highlighted as the most widely studied gene within the 22q11.2 region. Variants in this gene have resulted in conotruncal cardiac anomalies in animal models and humans. Several known human disease-causing genes that map to the region are indicated in gray boxes. These include proline dehydrogenase 1 (PRODH; associated with type I hyperprolinaemia), solute carrier family 25 member 1 (SLC25A1; encoding the tricarboxylate transport protein and is associated with combined D-2- and L-2-hydroxyglutaric aciduria), platelet glycoprotein Ib β-polypeptide (GP1BB; associated with Bernard–Soulier syndrome), scavenger receptor class F member 2 (SCARF2; associated with Van den Ende–Gupta syndrome), synaptosomal-associated protein 29 kDa (SNAP29; associated with cerebral dysgenesis, neuropathy, ichthyosis and palmoplantar keratoderma syndrome), and leucine-zipper-like transcription regulator 1 (LZTR1; associated with schwannomatosis 2 and autosomal recessive Noonan syndrome). Additional genes associated with autosomal recessive conditions include cell division cycle protein 45 (CDC45; associated with craniosynostosis, cleft lip/palate, gastrointestinal and genitourinary anomalies, skeletal differences and short stature; CGS syndrome, C—craniosynostosis, cleft lip/palate, G—gastrointestinal and genitourinary, S—skeletal and short stature; and Meier-Gorlin syndrome) and transport and Golgi organization 2 homolog (TANGO2; associated with metabolic crisis with rhabdomyolysis, seizures, hypoglycemia, thyroid disease, optic nerve atrophy, amblyopia, dysconjugate gaze, dysarthria, hypotonia, hypertonia, dystonia, hyperreflexia, clonus, positive Babinski, spastic Achilles tendons, multiple joint contractures, progressive microcephaly, cerebral atrophy, progressive intellectual disability, encephalopathy, cardiac arrhythmia, left ventricular hypertrophy, dilated cardiomyopathy, prominent trabeculations, decreased left ventricular function, long QT, torsades de pointes, and sudden death; TANGO2-related disorders). Common 22q11.2 deletions are shown, with the typical 3 Mb deletion flanked by LCR22A and LCR22D (LCR22A-LCR22D) on top and the nested deletions with their respective deletion sizes indicated below. Each of the deletions portrayed is flanked by a particular LCR22. Those rare deletions not mediated by LCRs are not shown. Additional genes in the region include AIF3M, apoptosis-inducing factor mitochondrion- associated 3; ARVCF, armadillo repeat gene; CLDN5, claudin 5; CLTCL1, clathrin heavy chain-like 1; COMT, catechol-O-methyltransferase; CRKL, v-crk avian sarcoma virus CT10 oncogene homologue-like; DGCR, DiGeorge syndrome critical region; GNB1L, guanine nucleotide-binding protein (G protein), β-polypeptide 1-like; GSC2, goosecoid homeobox 2; HIC2, hypermethylated in cancer 2; HIRA, histone cell cycle regulator; KLHL22, kelch-like family member 22; LINC00896, long intergenic non-protein-coding RNA 896; LOC101927859, serine/arginine repetitive matrix protein 2-like; CCDC188, coiled-coil domain-containing 188; LRRC74B, leucine-rich repeat-containing 74B; MED15, mediator complex subunit 15; mir, microRNA; MRPL40, mitochondrial ribosomal protein L40; P2RX6, purinergic receptor P2X ligand-gated ion channel 6; PI4KA, phosphatidylinositol 4-kinase catalytic-α; RANBP1, Ran-binding protein 1; RTN4R, reticulon 4 receptor; SEPT5, septin 5; SERPIND1, serpin peptidase inhibitor clade D (heparin co-factor) member 1; THAP7, THAP domain-containing 7; TRMT2A, tRNA methyltransferase 2 homologue A; TSSK2, testis-specific serine kinase 2; TXNRD2, thioredoxin reductase 2; UFD1L, ubiquitin fusion degradation 1-like; USP41, ubiquitin-specific peptidase 41; ZDHHC8, zinc-finger DHHC-type-containing 8; ZNF74, zinc-finger protein 74. (Figure adapted with permission from McDonald-McGinn et al.
22q11.2DS is often suspected because of congenital abnormalities, primarily cardiac and speech/language deficits, learning/behavioral problems, recurrent infections, and subtle dysmorphic features. Occasional cases are identified via newborn screening for severe combined immunodeficiency.
Although awareness of 22q11.2DS has increased, the diagnosis is often delayed or missed, especially in those without serious congenital heart disease (CHD).
Subsequent research has highlighted important novel associations. The aim in this study was to systematically review the literature and provide updated recommendations to facilitate optimal care for children and adolescents with 22q11.2DS.
Materials and Methods
The 22q11.2 Society recruited expert clinicians worldwide to revise the original clinical practice guidelines for children through a stepwise process: (1) a systematic literature search, according to best practices (Preferred Reporting Items for Systematic Reviews and Meta-Analyses, 2020; Supplemental Figure 1),
guided by a methodologist, (2) study selection and synthesis by the clinical experts from 9 countries, covering 24 subspecialties, and (3) creation of a multidisciplinary consensus document using the Grading of Recommendations Assessment, Development and Evaluation framework (GRADE)
based on the literature and best practice and shaped by patient advocate survey results, with subsequent independent approval sought.
Inclusion criteria comprised any report with relevance to clinical care of individuals born with a 22q11.2 deletion involving the typical deletion region. Reports involving other conditions including distal 22q11.2 deletions or restricted to prenatal issues were excluded. Given the limited number of systematic studies in 22q11.2DS, a qualitative synthesis of the evidence was performed by a multidisciplinary panel of clinical experts, with review of all reports available from the systematic search.
Using the Grading of Recommendations Assessment, Development and Evaluation framework, high confidence evidence was deemed too limited to justify formal grading of individual recommendations with respect to the quality of available scientific literature or of fine gradations of strength.
Consensus recommendations were formulated based on the literature, consideration of being more beneficial than harmful, and best practice according to the experts involved (each having seen tens to hundreds of patients), and input from patient advocate survey results. The revised guidelines were subsequently approved for submission by 2 external reviewers (parent of a child with 22q11.2DS and a genetics expert), neither of whom were part of the guidelines updating process.
The systematic literature search initially identified 6018 publications regarding 22q11.2DS across the lifespan (Supplemental Figure 1); 3577 were excluded after initial screening (most were duplicates, or involved other conditions) and 97 could not be retrieved, resulting in 2344 reports included for full-text review. Thereafter, 26 reports were excluded as they had no relevance to clinical care. Of the final 2318 that met the inclusion criteria (list included in Supplemental Material, Study Selection and Data Extraction under Methods), 1545 were deemed to have potential relevance to children and adolescents.
The patient advocate survey results, completed by eight 22q11.2DS patient advocacy organizations, based in 7 countries on 3 continents and representing 7624 families, supported updated guidelines to improve: awareness for health care providers and the public; access to 22q11.2DS specific clinics, knowledgeable providers, and comprehensive care; and access to genetic testing and genetic counseling. The respondents ranked the top 5 most relevant subspecialty areas of care, through a combination of free responses and checkboxes of predetermined options as (1) cardiology, (2) brain and behavior (psychiatry, neurology, early intervention, education), (3) genetics (testing, counseling, reproductive health), (4) ear, nose, and throat (ENT) (chronic infections, hearing, palate), and (5) immunology, rheumatology, hematology, and oncology. Regarding knowledge transfer, the respondents conveyed a need for guidelines to be shareable, portable, and available on the internet/social media.
The vast majority of scientific literature relevant to clinical management of children with 22q11.2DS involved study designs in low confidence categories,
with few randomized clinical trials, formal systematic reviews, or meta-analyses. Given the state of the scientific evidence available and the challenges inherent to 22q11.2DS that include multiple comorbidities and high inter-individual variability, recommendations in these updated guidelines were not formally graded on an individual basis.
The recommendations rather emphasize those with lowest harm and highest potential benefit for patients with this rare condition, informed by long term experience with patients and their families, that reflect current best practice.
Pediatric care for patients with 22q11.2DS requires both generalists and specialists in multiple fields to appreciate the overall interrelated effects of associated medical and developmental features and their impact on well-being and quality of life. Basic knowledge about variable expressivity, severity of features, and changes over time, as well as an emphasis on family-centered care,
Periodic assessments may identify new or anticipated features enabling early treatment. Preventive management of developmental issues can mitigate frustration and support achieving full potential. Coordination of care with multidisciplinary evaluations is required. Relatives, including parents, siblings, and often grandparents, benefit from information and support. Optimizing health, functioning, and quality of life is the overall goal of these recommendations.
We summarize main features and management recommendations by system in the following sections and in corresponding tables. Figure 2 presents the multisystem features, and Table 1 highlights recommended assessments and health monitoring at diagnosis and by age. In addition, important “Do’s” and “Do not’s” are provided in Table 2. In this, international/local differences should be considered. Of note, these recommendations are most relevant to high-income countries and corresponding resources.
Figure 2Features and risks in children and adolescents with 22q11.2 deletion syndrome.Figure 2 presents the associated multisystem features observed in children and adolescents with 22q11.2 deletion syndrome. The relative prevalence of each feature is indicated as a gradient of blue, with the darkest shade indicating the most common, intermediate blue specifying less common, and pale blue signifying rare but clinically relevant. White boxes denote features that may be commonly associated but do not necessarily require clinical attention. ADHD, attention deficit hyperactivity disorder; CL/P, cleft lip/palate; AHA, autoimmune hemolytic anemia; ITP, immune thrombocytopenia; NG/G, nasogastric/gastric; NVLD, nonverbal learning disorder; SMCP, submucous cleft palate; TEF, tracheoesophageal fistula.
Consider velopharyngeal port imaging (eg, nasopharyngoscopy or speech videofluoroscopy) with cleft team (SLP and surgeon) when adequate speech output and articulation skills are present to allow for valid diagnostic imaging.
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Evaluation of speech and language by speech-language pathologist
Increased risk for obstructive sleep apnea after VPD surgery.
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Cognitive development, academic functioning, and child psychiatry
Assessment of cognitive/learning capacities including language domains with standardized measures
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Assessment of adaptive functioning (eg, daily living skills)
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Psychiatric assessment (ASD, ADHD/ADD, anxiety, and psychotic disorders)
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Table 1 provides recommendations for periodic assessment and management of children and adolescents with 22q11.2 deletion syndrome at diagnosis, annually/biannually, and by age.
a Proband and parents; strategy depending on test availability.
b When rare recessive condition associated with 22q11.2 region is suspected or atypical phenotypic features observed.
c Having seen many pediatric patients with 22q11.2DS both in consultation and in follow-up.
d Applies to children with and children without known CHD.
e Consider velopharyngeal port imaging (eg, nasopharyngoscopy or speech videofluoroscopy) with cleft team (SLP and surgeon) when adequate speech output and articulation skills are present to allow for valid diagnostic imaging.
f Should include assessment of speech (eg, articulation, resonance, voice), receptive and expressive language, and social/pragmatics skills.
g Dental assessment not relevant before age 2 years.
h Consider videofluoroscopic swallow study or fiberoptic endoscopic evaluation of swallowing if any signs or symptoms of aspiration.
i T cell phenotyping; CD3, CD4, CD8 cell counts (+ CD4/CD45RA). B cell count (CD19) and switched memory B cells (CD19 or CD20+, CD27+IgM-).
j Include antibodies against tetanus, diphtheria, and pneumococci.
k Especially important before VPD surgery to exclude instability; can be performed from age 4 years when sufficient bony ossification has occurred.
l Increased risk for obstructive sleep apnea after VPD surgery.
perform parental studies even if both parents have negative histories because parents may be mildly affected and somatic and germline mosaicism are possible,
The correlation between severity of postoperative hypocalcemia and perioperative mortality in chromosome 22q11.2 microdeletion (22q11DS) patient after cardiac-correction surgery: a retrospective analysis.
Social cognition dysfunction in adolescents with 22q11.2 deletion syndrome (velo-cardio-facial syndrome): relationship with executive functioning and social competence/functioning.
Psychiatric disorders from childhood to adulthood in 22q11.2 deletion syndrome: results from the International Consortium on Brain and Behavior in 22q11.2 Deletion Syndrome.
Designate 1 clinician to coordinate medical and health-related social needs, be familiar with the important common and rare associated features, recognize that symptoms change over time and family members/caregivers are essential members of the team
Expect the adolescent with 22q11.2DS to present all their symptoms without prompts, overwhelm families with a list of nonactionable associated features, exclude family members from participating in care discussions
Table 2 presents important management tips in the form of “Do’s” and “Do not’s” for 16 topic areas pertinent to clinicians caring for children and adolescents with 22q11.2 deletion syndrome.
CBC, complete blood count; CNS, central nervous system; OSA, obstructive sleep apnea; VPD, velopharyngeal dysfunction.
22q11.2DS is a contiguous gene deletion syndrome. Affected individuals have a heterozygous loss of 1 copy of the chromosome 22q11.2 region. Most deletions occur as de novo events but approximately 10% are inherited from a parent.
most commonly LCR22A to LCR22D (85%-90%), resulting in an approximately 2.5 to 3 megabase (Mb) deletion involving approximately 50 protein-coding genes.
Rarer LCR22B to LCR22D and LCR22C to LCR22D deletions (∼5%) occur with overlapping features as this region includes the important developmental gene CRKL associated with congenital heart disease and renal anomalies.
Distal deletions beyond LCR22D (involving other LCRs, LCR22E to LCR22H, OMIM 611867), comprising a distinct entity, should not be confused with 22q11.2DS and are not the subject of these recommendations.
Beginning in the 1990’s, the 22q11.2 deletion was identified using fluorescence in situ hybridization (FISH) and probes located between LCR22A-LCR22B.
but both tests required an elevated index of suspicion. Chromosomal microarray analysis (CMA) identifies genome-wide copy number variants (CNVs), thus 22q11.2 deletions and their breakpoints and in a minority of patients any other relevant CNVs if present.
Even the common 2.5 Mb deletion is usually submicroscopic, ie, missed in karyotyping except for rare unbalanced translocations. Thus, CMA currently provides the most clinically useful information for diagnosis and genetic counseling, but we acknowledge that it may not be available or covered in many settings around the world.
Occasionally, the 22q11.2 deletion may uncover a pathogenic variant or small CNV involving a disease-producing gene in the remaining allele, unmasking an autosomal recessive condition. Examples include PRODH (hyperprolinemia),
If atypical features are noted, targeted or exome/genome sequencing should be considered to identify single nucleotide variants or small CNVs on the remaining intact allele.
Genetic counseling
Parental testing is always recommended to determine whether the 22q11.2 deletion is de novo or transmitted from a parent to provide care and genetic counseling for the affected parent.
This includes the opportunity to identify the rare parent with somatic mosaicism. Parents of a child with a de novo deletion have a small increased recurrence risk over the general population based on reports of germline mosaicism.
Reproductive counseling will include discussions regarding prenatal screening/definitive testing options. Affected individuals, both males and females, have a 50% chance of having a child with 22q11.2DS in each pregnancy. In addition to care recommendations, as for any newly diagnosed individual, risk of transmission and variable expressivity are key discussion points. Available reproductive options including prenatal screening and preconception options such as preimplantation genetic diagnostics using in vitro fertilization should also be reviewed.
Prenatal considerations
Prenatal features may be observed on fetal ultrasound/echocardiogram in the first trimester, but more commonly at ≥20 weeks’ gestation. Cardiac anomalies are frequently associated but extracardiac abnormalities, affecting all systems, can be present in as many as 90%.
Expanding the fetal phenotype: prenatal sonographic findings and perinatal outcomes in a cohort of patients with a confirmed 22q11.2 deletion syndrome.
However, not all congenital features are appreciated prenatally (eg, laryngeal web). Ultrasound anomalies warrant referral to maternal-fetal medicine and genetic counseling. Prenatal diagnostic testing via chorionic villus sampling or amniocentesis is recommended to optimize delivery planning. CMA remains the most comprehensive test.
Noninvasive prenatal screening is bringing some affected pregnancies, and previously undiagnosed mothers, to attention but it requires confirmatory diagnostic testing.
Effects of platforms, size filter cutoffs, and targeted regions of cytogenomic microarray on detection of copy number variants and uniparental disomy in prenatal diagnosis: results from 5026 pregnancies.
Noninvasive prenatal testing for trisomies 21, 18, and 13, sex chromosome aneuploidies, and microdeletions in average-risk pregnancies: a cost-effectiveness analysis.
Expanding the fetal phenotype: prenatal sonographic findings and perinatal outcomes in a cohort of patients with a confirmed 22q11.2 deletion syndrome.
Expanding the fetal phenotype: prenatal sonographic findings and perinatal outcomes in a cohort of patients with a confirmed 22q11.2 deletion syndrome.
Fetuses with a 22q11.2 deletion may be considered high risk for pregnancy/delivery given elevated prevalence of late preterm births and intrauterine growth restriction.
Additional severity may be conveyed by associated pulmonary atresia, major aortopulmonary collaterals, and/or discontinuity of pulmonary arteries. Other congenital anomalies, including crossed pulmonary arteries, aberrant subclavian artery, and aortic arch anomalies, may raise clinical suspicion both as isolated findings or as associated with CTD.
Vascular anomalies may cause a vascular ring that can compress the trachea/esophagus, manifesting as stridor/feeding and swallowing difficulties and may require studies beyond an echocardiogram, such as a chest MRI, for confirmation.
CTDs usually require intracardiac repair in infancy or early childhood, necessitating syndrome-specific perioperative and multidisciplinary management to minimize increased complication risk; eg, prolonged mechanical ventilation and length of hospital stay.
22q11.2 Deletion syndrome is associated with increased perioperative events and more complicated postoperative course in infants undergoing infant operative correction of truncus arteriosus communis or interrupted aortic arch.
Palatal abnormalities are seen in about two-thirds of children and typically include velopharyngeal dysfunction (VPD) with or without a formal diagnosis of submucous cleft palate (SMCP), with overt cleft palate and cleft lip/palate occurring less frequently.
The inability of the soft palate and pharyngeal walls to close properly during speech may be complicated by anatomical and functional factors such as palatal clefting, altered velopharyngeal dimensions, cranial nerve abnormalities, and velopharyngeal muscle hypoplasia. This may result in severe VPD with hypernasality, compensatory articulation patterns, and poor intelligibility.
Children often present with a complex communication profile including structural, neurologic, developmental, and cognitive speech-language disorders and social/pragmatic deficits that vary with regards to time of presentation and clinical profile. Emergence of speech and language is typically delayed, with high prevalence of both receptive and expressive language delays/disorders including apraxia. More pronounced expressive deficits are often evident in preschool years.
Speech/language assessments are required beginning at 6-18 months and routinely thereafter.
Overt palatal clefts are typically repaired around age 1 year. SMCP or VPD should be assessed jointly with speech-language pathologists, including evaluation with velopharyngeal imaging (nasendoscopy/videofluoroscopy) when VPD is clinically suspected and once adequate speech is present.
Many children require intensive speech-language therapy throughout childhood. Progress may be slow because of cognitive/learning and behavioral differences.
Defining risk of postoperative obstructive sleep apnea in patients with 22q11.2DS undergoing pharyngeal flap surgery for velopharyngeal dysfunction using polysomnographic evaluation.
Defining risk of postoperative obstructive sleep apnea in patients with 22q11.2DS undergoing pharyngeal flap surgery for velopharyngeal dysfunction using polysomnographic evaluation.
Defining risk of postoperative obstructive sleep apnea in patients with 22q11.2DS undergoing pharyngeal flap surgery for velopharyngeal dysfunction using polysomnographic evaluation.
Airway anomalies, including laryngomalacia, tracheomalacia, subglottic stenosis, glottic web, vocal fold paralysis, and laryngeal cleft, occur in approximately 20% of children.
Symptoms include stridor/noisy breathing, aspiration, and need for supplemental oxygen with a subset (often those with concomitant CHD) requiring tracheostomy. Screening should occur routinely with formal airway evaluation recommended as symptoms warrant.
For patients with chronic otitis media with effusion, myringotomy with ear tube placement should be considered to optimize hearing. Occasionally hearing loss is severe, requiring hearing aids.
Ocular findings are common including strabismus, refractive errors (hyperopia and astigmatism), and incidental features (retinal vascular tortuosity, posterior embryotoxon, eyelid hooding).
Common dental abnormalities, including caries, impaired saliva secretion, enamel defects, and malocclusions can affect general health and quality of life.
Caries prevention includes oral hygiene, fluorides, and sealants. Some children need examination/treatment under anesthesia. For CHD-related endocarditis risk, consult national guidelines regarding preventive antibiotics.
Defining risk of postoperative obstructive sleep apnea in patients with 22q11.2DS undergoing pharyngeal flap surgery for velopharyngeal dysfunction using polysomnographic evaluation.
Transient neonatal hypocalcemia may occur, and hypocalcemic seizures may be the first sign of 22q11.2DS. Hypocalcemia can recur during periods of biologic stress, eg, perioperative, with acute illness, puberty, in pregnancy, or decreased oral intake,
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