Deletion Syndrome

Once a patient presents with symptoms that may be suspected as 22q11.2 deletion syndrome, several tests have to be conducted in order to determine if this is in fact the cause. With our proband, it is clear that this is a case of familiar inheritance. As a clinician, is it important to start by asking about the patient’s current and past medical history, history of present illness, developmental and social functioning and obstetric history so we can get a more in depth understanding of the patient’s presentation (“22q11.2 Deletion Syndrome”, 2016). A physical exam is also necessary to assure that there is nothing that we may be missing, or that the patient failed to report. Often further clues can be provided from inspecting and examining the
patient. Blood tests can also be done to check if there are any abnormalities that may not necessarily be related to a phenotypic condition and are likely causing some of the symptoms that the patient may or may not be aware of.
Some of the pertinent blood tests would include thyroid function, parathyroid function, complete blood cell count, immunologic evaluation, and calcium levels. Findings can bring light to some of the other complications that are going on with the patient that they may not be associating with their current state of health (Bassett et al., 2011). I would also suggest that the proband’s daughter be seen by a physician and go through the same procedures of history taking, physical examination, and be sent for further diagnostic testing. Some of the other evaluations suggested upon initial diagnosis that were not mentioned include: a baseline cardiac evaluation (with chest x-ray, ECG, and echo), a renal ultrasound, an ophthalmology evaluation, audiology evaluation, chest x-ray for evaluating thoracic vertebral anomalies, and evaluation of the palate (McDonald-McGinn et al.,
2013).

In terms of genetic testing, I would recommend that our proband as well as her daughter have multiple tests.
Currently in the U.S., fluorescence in situ hybridization (FISH) with probes such as TUPLE1 and N25 (Bassett et al., 2011), is the most commonly used method for detecting 22q11.2 microdeletions (Hacıhamdioğlu et al., 2015). While it is found to be a highly accurate test with significant reliability, and is commonly used for prenatal diagnosis as well, it is limited to a single target sequence within the deletion region, meaning that some atypical deletions that are not included in this region can be missed. While approximately 85% of 22q11.2 deletion syndrome patients have a large deletion that will likely be detected by FISH studies, the remaining patients with smaller or atypical deletions, may go undetected (Bassett et al., 2011). A test thought to be more sophisticated due to its ability to detect deletions of all sizes, is the multiplex ligand-dependent probe amplification (MLPA). The MLPA is found to be a more cost-effective method, with quicker results, and has the ability to detect smaller deletions and ones that may have been missed by FISH. MLPA is now becoming increasingly more accepted in the U.S (Hacıhamdioğlu et al., 2015). Chromosomal microarray (CMA) can also be used to identify more atypical and smaller deletions. According to McDonald-McGinn et al. (2013), Chromosomal microarray tests are the most suitable studies to be ordered to identify the
deletion in a proband when phenotype is nonspecific and are commonly seen used when evaluating a patient with developmental abnormalities. CMA can identify a large variety of chromosomal abnormalities that may be causing the symptoms presented (McDonald-McGinn et al., 2013). Methods such as FISH and MLPA are used more commonly for targeted deletion analysis, including confirmation of deletion following CMA, testing proband’s relatives for the deletion, or for when rapid diagnosis is necessary if 22q11.2 deletion syndrome is suspected (McDonald-McGinn et al., 2013). Because there is such a wide variety of testing, with very specific guidelines as to which test is most appropriate for which patient, this may be something that I would refer to a genetic counseling specialist who may decide what tests are best ordered for this patient and her daughter.