DiGeorge syndrome and genetics
DiGeorge syndrome, also known as velocardiofacial syndrome or chromosome 22q11 deletion syndrome, is a rare genetic disorder present at birth that can lead to a range of health issues. It is primarily caused by a deletion on chromosome 22 at the 22q11.2 location, which typically results in the loss of about two million DNA base pairs, affecting around forty genes. This genetic alteration can lead to symptoms such as immune deficiency, heart defects, cleft palate, and characteristic facial features, including an elongated face and almond-shaped eyes. The severity of symptoms can vary, with more than 90% of cases arising from new deletions rather than inherited ones. Certain genes within the deleted region, like TBX1, HIRA, and UFD1L, have been implicated in the syndrome’s manifestations, particularly concerning heart defects and neurological development. Diagnosis often involves a combination of medical history, physical examination, blood tests, and genetic testing. While there is currently no known prevention for DiGeorge syndrome, treatments may include thymic tissue or bone marrow transplants to improve immune function, particularly in infants. Overall, the condition is lifelong, but early diagnosis and intervention can help manage symptoms effectively.
DiGeorge syndrome and genetics
ALSO KNOWN AS: Velocardiofacial syndrome; chromosome 22q11 deletion syndrome
DEFINITION DiGeorge syndrome is a rare genetic disease present at birth and is associated with recurrent infection, heart defects, and characteristic facial features. People with complete DiGeorge syndrome have no thymus or parathyroid glands.
Risk Factors
Maternal diabetes is thought to increase the risk of DiGeorge syndrome.
Etiology and Genetics
DiGeorge syndrome results from the deletion (loss) of a small part of the long arm of chromosome 22 at position 22q11.2. Most people with this deletion are missing about two million base pairs of deoxyribonucleic acid (DNA), which corresponds to about forty genes, although some patients have shorter deletions in the same region. The degree of phenotypic expression in different individuals seems to be related to the size of the deletion. There have been sporadic reports of patients with similar symptoms who have deletions on other chromosomes (at positions 10p13, 17p13, and 18q21).
Efforts to identify the one or two genes in the 22q11.2 band that are most critical to the expression of the syndrome have largely been unsuccessful, and it appears likely that the diminished expression of several related genes affecting common developmental processes is responsible. Three genes, however, have been identified that may be particularly important. The TBX1 gene, which encodes the T-box transcription factor 1, is probably responsible for the heart defects characteristic of the syndrome. A gene called HIRA specifies another transcriptional regulator that acts early in the development of the nervous system, and the gene UFD1L codes for a protein involved in the degradation pathway of ubiquinated compounds.
The 22q11.2 deletion characteristic of DiGeorge syndrome can be inherited, but this is only rarely the case in new diagnoses. More than 90 percent of affected individuals have a de novo deletion, and fewer than 10 percent have an affected parent. Apparently the 22q11.2 region has a chromosomal structure that makes it occasionally susceptible to breakage during genetic recombination events that occur naturally during sperm and egg development. According to information from the US National Library of Medicine, the 22q11.2 deletion occurred in about 0.1 percent of fetuses and 1 in 4,000 to 6,000 live births.
Symptoms
Features of DiGeorge syndrome are present at birth and do not worsen with age. Features may include immune deficiency leading to increased infections, cleft palate, heart defects, failure to thrive, small head, increased incidence of psychiatric disorders, and characteristic facial features, including elongated face, almond-shaped eyes, wide nose, and small ears. Other features of the disease may be learning difficulties; hypoparathyroidism, a disorder in which insufficient parathyroid hormone is secreted from the parathyroid glands, resulting in abnormally low levels of calcium in the blood; weak muscles; and short height. Occasional abnormalities include structural brain defects, scoliosis, umbilical or inguinal hernias, kidney abnormalities, anogenital abnormalities, eye abnormalities, thyroid problems, and tapered and hyperextensible fingers.
Screening and Diagnosis
The doctor will ask about a patient’s symptoms and medical history and will perform a physical exam. Other tests may include blood tests to rule out other conditions, detect parathyroid hormone levels, and discover immune problems; genetic tests to look for deletions in chromosome 22; and a chest x-ray, a test that uses radiation to take pictures of structures inside the body, especially to determine if the thymus is present.
Treatment and Therapy
Patients should talk with their doctors about the best plans. In infants, thymic tissue transplantation or bone marrow transplantation may help restore immune function, but the risks and benefits of these procedures must be carefully considered.
Prevention and Outcomes
There is no known way to prevent DiGeorge syndrome.
Bibliography
Baker-Gomez, Sherry. Missing Genetic Pieces: Strategies for Living with VCFS, the Chromosome 22q11 Deletion. Phoenix: Desert Pearl, 2004. Print.
Cutler-Landsman, Donna, ed. Educating Children with Velo-Cardio-Facial Syndrome. 2d ed. San Diego: Plural, 2013. Print.
Jones, Kenneth L. Smith’s Recognizable Patterns of Human Malformation. 7th ed. Philadelphia: Elsevier Saunders, 2013. Print.
Kleigman, Robert M., et al., eds. Nelson Textbook of Pediatrics. 19th ed. Philadelphia: Saunders; 2011. Print.
Lackey, Alexandra E., and Maria Rosaria Muzio. “DiGeorge Syndrome.” National Library of Medicine, 8 Aug. 2023, www.ncbi.nlm.nih.gov/books/NBK549798/. Accessed 9 Sept. 2024.
"About Velocardiofacial Syndrome." National Human Genome Research Institute, 29 June 2017, www.genome.gov/Genetic-Disorders/Velocardiofacial-Syndrome. Accessed 9 Sept. 2024.
Shprintzen, Robert J., and Karen J. Golding-Kushner. Velo-Cardio-Facial Syndrome. 2 vols. San Diego: Plural, 2008–9. Print.
"22Q11.2 Deletion Syndrome." Medline Plus, 1 Dec. 2019, medlineplus.gov/genetics/condition/22q112-deletion-syndrome/. Accessed 9 Sept. 2024.