Microdeletions and Microduplications. These chromosomal deletions or duplications-smaller than 3 to 5 million base pairs-are too small to be detected with standard karyotyping. However, prenatal chromosomal micro array analysis (CMA) , described later (p. 271), permits identification of syndromes associated with these microdeletion or duplications. When CMA is used, the region of DNA that is missing or duplicated is termed a genomic copy number variant. Despite the relatively small size, a microdeletion or duplication may involve a stretch of DNA that contains multiple genes-causing a contiguous gene syndrome, which can encompass serious but unrelated phenotypic abnormalities (Schmickel, 1986). In some cases, a micro duplication may involve the exact DNA region that causes a recognized microdeletion syndrome (Table 13-2). When a speciic microdeletion syndrome is suspected clinically, it is confirmed using either CMA or luorescence in situ hybridization.
22qlel.2 Microdeletion Syndrome. his syndrome is also known as DiGeorge syndrome, Shprintzen syndrome, and velocardiofacial syndrome. It is the most common microdeletion, with a prevalence of 1 in 3000 to 6000 births. Although inherited in an autosomal dominant fashion, more than 90 percent of cases arise from de novo mutations. The full deletion includes 3 million base pairs, encompasses 40 genes, may include 180 diferent features, and thus poses some counseling challenges (Shprintzen, 2008). Features can vary widely, even among afected family members. Previously, diferent constellations of features were thought to characterize the DiGeorge and Shprintzen phenotypes, but it is now accepted that they represent the same microdeletion (McDonald-McGinn, 2015).
In approximately 75 percent of afected individuals, associated abnormalities include conotruncal cardiac anomalies,
Prevalence reflects live births.
Data from National Library of Medicine, 2017; Johns Hopkins University, 2017.
such as tetralogy of Fallot, truncus arteriosus, interrupted aortic arch, and ventricular septal defects (McDonald-McGinn, 2015). Immune deiciency, such as T-cell lymphopenia, also develops in approximately 75 percent. More than 70 percent have velopharyngeal insuiciency or cleft palate. Learning disabilities, autism spectrum disorder, and intellectual disability are also common. Other manifestations include hypocalcemia, renal anomalies, esophageal dysmotility, hearing loss, behavioral disorders, and psychiatric illness-particularly schizophrenia. Short palpebral issures, bulbous nasal tip, micrognathia, short philtrum, and small or posteriorly rotated ears are characteristic facial features.
hese are DNA rearrangements in which a segment of DNA breas away from one chromosome and attaches to another. he rearranged chromosomes are called derivative (der) chromosomes. here are two types-reciprocal and robertsonian translocations.