Deaths of the Young and Elderly
John M. Wayne, Cynthia A. Schandl, S. Erin Presnell in Forensic Pathology Review, 2017
Answer B is correct. DiGeorge syndrome, also known as velocardiofacial syndrome or 22q11.2 deletion syndrome, demonstrates a constellation of features that often includes thymic hypoplasia or aplasia and cardiac defects that range in severity from asymptomatic (small aortic coarctation) to emergent (tetralogy of Fallot). The neonate may present with hypocalcemia as the parathyroid glands may also be abnormal. Other midline abnormalities such as cleft palate may result in feeding difficulties. DiGeorge syndrome may be detected by chromosomal microarray studies and usually also by FISH analysis with deletion of one 22q11.2 probe signal; however, a normal FISH analysis does not exclude DiGeorge syndrome, which is a compendium of clinical findings. Since many individuals with DiGeorge syndrome can be sufficiently managed medically and surgically, the case described is also worrisome for neglect, which should be investigated along with studies to demonstrate the suspected genetic abnormality. Note also that an ectopic thymus gland may be present, but not found by autopsy, so additional evidence for the syndrome should be present before making this diagnosis (such as genetic evidence).
D-2-hydroxyglutaric (DL-2-hydroxyglutaric) aciduria
William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop in Atlas of Inherited Metabolic Diseases, 2020
In the combined D-2 and L-2 hydroxyglutaric patients in whom the fundamental defect is in SLC25A1, the gene for the citrate carrier CIC. Deficiency impairs the efflux of citrate and isocitrate from mitochondria in exchange for malate. This leads to depletion of cytosolic citrate and accumulation of mitochondrial citrate. The gene is on chromosome 22q11 in the area deleted in DiGeorge syndrome. A variety of mutations was found in 12 patients, eight of whom were homozygous [12]. Missense mutations such as c.844C>T were the most common; there was one nonsense mutation, two frameshifts and a mutation which caused a splicing error. In two patients, no protein was detected on immunoblot.
Genetics
Stephan Strobel, Lewis Spitz, Stephen D. Marks in Great Ormond Street Handbook of Paediatrics, 2019
DiGeorge syndrome is due to a monoallelic deletion of chromosome 22q11 (del22q11.2) (Fig. 15.13). These microdeletions are typically ~3 Mb of genomic DNA and are not detectable by G-banded karyo-type. The TBX1 gene within the area of deletion is of particular importance in the phenotype.
Current updates and future perspectives in the evaluation of azoospermia: A systematic review
Published in Arab Journal of Urology, 2021
Nahid Punjani, Caroline Kang, Dolores J. Lamb, Peter N. Schlegel
CRKL encodes the SRC homology 2 (SH2) and SH3 homology adaptor protein that plays a role in mediating tyrosine kinase signalling pathways [54]. This well-known gene causes many of the major anomalies present in 22q11.2 deletion syndrome (DiGeorge syndrome) and was more recently defined as the gene-dosage defect that causes the genitourinary abnormalities found in both DiGeorge syndrome and seemingly non-syndromic patients with upper and lower tract genitourinary anomalies. Associated birth defects included micropenis and cryptorchidism, but the histopathology identified in the cryptorchid mouse model was atypical spermatogenic failure unlike the spermatogenic arrest present in individuals (or mice) with cryptorchid testis [54]. This protein therefore has a unique role in testicular descent, spermatogenesis, and like MAZ described above is associated with numerous other systemic conditions such as cardiac, developmental, gastrointestinal, ocular, auditory, and craniofacial abnormalities [3].
Evaluation and Maintenance of Behavioral Interventions for 22q11.2 Deletion Syndrome
Published in Developmental Neurorehabilitation, 2022
Louis Busch, Valdeep Saini, Sidrah Karim, Roland Jones
22q11.2 deletion syndrome (22q11DS), also known as DiGeorge syndrome, velocardiofacial syndrome, and conotruncal anomaly face syndrome, is a genetic deletion syndrome caused by hemizygous deletion of the q11.2 part of chromosome 22.1,2 Estimated to occur in 1 in 4,000 live births, 22q11.2 deletion can be inherited as an autosomal dominant or arise as a de novo deletion or translocation.3–6
Related Knowledge Centers
- Chromosome 22
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- Global Developmental Delay
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