The Child with a Syndrome
John C Watkinson, Raymond W Clarke, Christopher P Aldren, Doris-Eva Bamiou, Raymond W Clarke, Richard M Irving, Haytham Kubba, Shakeel R Saeed in Paediatrics, The Ear, Skull Base, 2018
22q11 deletion syndrome encompasses the clinical conditions previously termed velocardiofacial syndrome and Di George syndrome which are now known to be different manifestations of the same genetic defect. A variety of clinical features can occur but not in every child.10 Common features include submucous cleft palate, congenital heart anomalies, absent thymus with impairment of T-cell immunity (Di George sequence) and characteristic facial features. The ENT clinical features result from abnormal development of structures derived from the third and fourth pharyngeal pouches. The first presentation to medical services may well be with recurrent episodes of AOM due to the impaired T-cell immunity. Another presentation to the otolaryngologist is with a congenital glottic web which is almost always diagnostic of 22q11 deletion (see Chapter 30, Congenital disorders of the larynx, trachea and bronchi).11,12 Again, the phenotypic profile is highly variable and awareness and suspicion are key. If there is suspicion of 22q11, full ENT assessment including laryngoscopy should be performed and referral to a geneticist and cardiologist initiated.13
Vascular rings
Prem Puri in Newborn Surgery, 2017
Double aortic arch is associated with a chromosome band 22q11 deletion in approximately 20% of patients. Band 22q11 deletion is responsible for DiGeorge, velocardiofacial, and conotruncal anomaly face syndromes, which are often referred to using the unified terms CATCH-22 syndrome and chromosome band 22q11 deletion syndrome. In patients with double aortic arch, the frequency of phenotypes satisfying the clinical criteria for these various syndromes is not known. Rather, the important point is that double aortic arch may be associated with band 22q11 deletion, which has various other possible manifestations. These include, but are not limited to, palatal abnormalities, laryngotracheal anomalies, speech and learning delay, characteristic facial features, hypocalcemia, abnormalities of T-cell-mediated immune function, and neurologic defects.
Non-Invasive Prenatal Testing (NIPT)
Carlos Simón, Carmen Rubio in Handbook of Genetic Diagnostic Technologies in Reproductive Medicine, 2022
SAs may result in physical and/or intellectual impairments that can be highly variable and dependent on the specific chromosomal region affected and the amount of duplicated or deleted genetic material (51). SAs in general are common and do not increase with maternal age, unlike the common trisomies. Pathogenic CNVs can occur across the genome, but around 25% are recurrent (52). The most common is the 22q11.2 deletion, which causes DiGeorge syndrome, with a frequency of 1 in 992 in a low-risk obstetric population (Grati et al., 2015) (52). Although NIPT has the potential to include CNV screening, most commercial platforms only report the detection of the most common recurrent microdeletion syndromes, with few detecting all CNVs that are 7 Mb or greater (18): 5p− (cri-du-chat syndrome), 22q11.2− (DiGeorge syndrome), 15q− (Prader–Willi/Angelman syndrome), 4p− (Wolf–Hirschhorn syndrome), and 1p36 (53) (Table 26.4).
Genetic Testing Is Messier in Practice than in Theory: Lessons from Neonatology
Published in The American Journal of Bioethics, 2022
Katharine Press Callahan, Chris Feudtner
Again, let’s illustrate with another hypothetical case. Consider a fetal patient with renal anomalies. Whole exome sequencing is sent. The patient is diagnosed with a variant of 22q11.2 deletion syndrome. While other specific deletions causing this syndrome are associated with renal anomalies (Lopez-Rivera et al. 2017), this particular deletion has not been previously associated. Her genetic diagnosis is more certainly associated with an increased risk of developing psychiatric disease in adulthood. Where on the framework would this genetic information fall and who would be responsible to decide? Does this diagnosis meet the proposed threshold for which 70% of women would consider termination? If a woman did opt for termination, would this decision have been based on the renal anomaly or the risk of psychiatric disease?
Prevalence and incidence of psychotic disorders in 22q11.2 deletion syndrome: a meta-analysis
Published in International Review of Psychiatry, 2022
Umberto Provenzani, Stefano Damiani, Ilaria Bersano, Simran Singh, Antonella Moschillo, Tommaso Accinni, Natascia Brondino, Dominic Oliver, Paolo Fusar-Poli
The 22q11.2 deletion syndrome (22q11.2DS) is one of the most common syndromes caused by a rare Copy Number Variation, with a prevalence estimated at around 1/3000 to 1/6000 live births (McDonald-McGinn et al., 2015). In the majority of cases, it is caused by a 3 Mb hemizygous deletion in chromosomal region 22q11.2, de novo in 85–90% of cases (Delio et al., 2013; Swillen et al., 2000). The term is used to refer to a heterogeneous group of disorders that share the same genetic alteration: DiGeorge syndrome or velo-cardio-facial syndrome, Cono-Truncal Anomaly Face Syndrome, Opitz syndrome and CHARGE syndrome (coloboma, heart defects, atresia choanae, growth retardation, genital abnormalities, and ear abnormalities) (McLean-Tooke et al., 2007). It can affect both sexes, and it is present in different ethnic groups thus not being characteristic of Caucasians (McDonald-McGinn et al., 1999), but it has a higher prevalence in western countries (Park et al., 2007). The gold-standard diagnostic test is fluorescence in situ hybridisation (Bretelle et al., 2010), while other recent techniques include multiplex ligation-dependent probe amplification (which uses probes directed towards the entire 22q11 region) and microarray comparative genome hybridisation (Morrow et al., 2018).
Serum zonulin and claudin-5 levels in children with obsessive–compulsive disorder
Published in Nordic Journal of Psychiatry, 2020
Ümit Işık, Pınar Aydoğan Avşar, Evrim Aktepe, Duygu Kumbul Doğuç, Faruk Kılıç, Halil İbrahim Büyükbayram
Claudins are a multigene family of 20–24 kDa integral membrane proteins and 24 claudin proteins; these have been identified in humans [24,25]. The claudins are expressed in numerous tissues with claudins-3, -5, and -12 being expressed by brain endothelial cells with claudin-5 being the most enriched [26]. Claudin-5 is a transmembrane tight–junction protein that is strongly expressed in the BBB site and endothelial cells of the brain. The characteristics of the brain endothelial tight–junction complex are regarded to be dependent on claudin-5 cell–cell interaction, thus enabling this protein to play an important part in maintaining the integrity of the brain endothelial barrier. Hence, changes in the claudin-5 function can contribute to the paracellular route “opening” and enhanced permeability of the brain’s endothelial barrier [24]. The claudin-5 gene is located within 22q11.21 chromosome [9,24]. Individuals with the 22q11 deletion syndrome (22q11DS) have a 30-fold enhanced lifetime risk of developing schizophrenia and other neuropsychiatric conditions [27]. Claudin-5 expression has been studied in schizophrenia, and the authors suggested that the disruption of BBB may be a modifying factor in schizophrenia development [9,11]. Although OCD is common in 22q11DS [28], there is no study that has examined the relationship between OCD and claudin-5.
Related Knowledge Centers
- Chromosome 22
- Congenital Heart Defect
- Hearing Loss
- Intellectual Disability
- Kidney Failure
- Schizophrenia
- Autoimmune Disease
- Rheumatoid Arthritis
- Global Developmental Delay
- Cleft Lip & Cleft Palate