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
Velo-cario-Facial Syndrome
Merlin G. Butler, F. John Meaney in Genetics of Developmental Disabilities, 2019
Velo-cardio-facial syndrome (VCFS) is a relatively common genetic disorder that affects about 1 in 2000 individuals (1). Caused by a microdeletion on chromosome 22q.11 (2,3), the syndrome is associated with multiple congenital anomalies and learning disabilities (4–8). The phenotypic spectrum of VCFS may be the most pleiotropic of any genetic syndrome. Over 180 clinical features have been reported in individuals with VCFS (1,9) with none being obligatory findings. Individuals with VCFS may have as few as four or five anomalies or over 50 depending on the severity of expression of the syndrome. Arguably, the most frequently described features of VCFS are behavioral, cognitive, and developmental problems (9).
Genetics
Rachel U Sidwell, Mike A Thomson in Concise Paediatrics, 2020
Deletion of a portion of the chromosome occurs, e.g. cri du chat syndrome (46,XY, del[5p]). Microdeletions (smaller deletions now visible microscopically using new techniques such as high-resolution banding and FISH, or by molecular techniques) include Williams syndrome (chromosome 7) and DiGeorge syndrome (chromosome 22, see p. 30).
Metyrosine treatment in a woman with chromosome 22q11.2 deletion syndrome and psychosis: a case study
Published in International Journal of Developmental Disabilities, 2019
Maria Hagen Engebretsen, Arvid Nikolai Kildahl, Iver Harald Hoy, Trine Lise Bakken
The chromosome 22q11.2 deletion syndrome (22q11.2 DS), also called DiGeorge syndrome or Velocardiofacial syndrome (VCFS), is a multiple anomaly disorder that is caused by a microdeletion of DNA. The 22q11.2 DS is more common than earlier studies indicate. A study of prenatal samples indicates a frequency of about 1 in 1000 (Grati et al. 2015). A number of medical and emotional conditions are associated with 22q11.2 DS, such as cardiovascular malformations, palatal abnormalities, facial dysmorphic features, immune deficiency, urogenital disorders, and mental illness (McDonald-McGinn et al. 2016, Schneider et al. 2014, Young et al. 2011). Cognitive impairments affect most people with 22q11.2 DS, including impaired attention, working memory, executive functions, and verbal learning (Young et al. 2011). Mean IQ is found to be about 70 and severe and profound ID is uncommon (McDonald-McGinn et al. 2016). Both behavior and social functioning may be affected negatively (Kates et al. 2015). An extremely high frequency of psychosis is found in patients with 22q11.2 DS (Monks et al. 2014, Schneider et al. 2014). A multi-site study including about 1400 persons with 22q11.2 DS aged 6-70 found psychotic disorders in 41% from age 25 (Schneider et al. 2014).
Clinical guidance on pharmacotherapy for the treatment of attention-deficit hyperactivity disorder (ADHD) for people with intellectual disability
Published in Expert Opinion on Pharmacotherapy, 2020
Jonjo Miller, Bhathika Perera, Rohit Shankar
Velocardiofacial syndrome (VCFS) can be associated with ID. No papers looking at solely people with ID and VCFS were identified. However, Green [51] published a trial in 34 patients with VCFS given MPH, which found a clinically significant improvement in 72% of patients, in whom the mean IQ was 82.8 (SD10.5). Gothelf [52] found in a 4 week prospective open-label observation study, in children with VCFS, low dose (0.3 mg/kg/od) MPH was effective in improving ADHD symptoms. The 12 patients treated came from an initial group of 18, in whom the mean IQ was 77.0 SD ± 15; however, for the treated patients, no exact IQ is stated. Mean CATQ score decreased by 49% after treatment; this was highly significant with p < 0.0001. Neuropsychological testing in the form of CCPT found significant improvements 1 h after MPH administration in omission errors, variability of reaction time, and ‘hits’ (all P < 0.05). There was a strong negative correlation between MPH improvement in CCPT index and IQ (r = −0.68, p = 0.01); useful negative evidence that the lower IQ group with VCFS responded sub-maximally.
Primary Immunodeficiency and Thrombocytopenia
Published in International Reviews of Immunology, 2022
Maryam Mohtashami, Azadehsadat Razavi, Hassan Abolhassani, Asghar Aghamohammadi, Reza Yazdani
The DiGeorge/velocardiofacial syndrome (DGS/VCFS) has been recognized as a frequent syndrome in humans and microdeletion of the 22q11.2 regions is introduced as the main cytogenic aberration in these patients. Cardiac defects, T-cells deficiencies and thrombocytopenia are reported in this syndrome [100, 101]. A high percentage of 22q11.2 deletion patients (more than 90%) are heterozygous for a deletion of the GPIb gene, hence, Bernard-Soulier syndrome (BSS) is expected in these patients supposing a reason for thrombocytopenia [54]. Macrothrombocytopenia is usually mild in BSS patients; however, another study has been reported that DGS patients with decreased count platelet have large mean platelet volume (MPV) and macrothrombocytopenia. On the other hand, immunologic responses are considered as the main factor of thrombocytopenia in some cases. Consequently, further studies are needed to determine thrombocytopenia prevalence in DGS patients [102, 103].
Related Knowledge Centers
- Chromosome 22
- Congenital Heart Defect
- Hearing Loss
- Intellectual Disability
- Kidney Failure
- Schizophrenia
- Autoimmune Disease
- Global Developmental Delay
- Cleft Lip & Cleft Palate
- Rheumatoid Arthritis