Investigations
1st investigations to order
serum calcium
Test
Hypocalcaemia may occur due to hypoparathyroidism.
Result
low
serum intact PTH
Test
Hypoparathyroidism may be seen due to failure of embryological development of the parathyroid glands. It is associated with a higher likelihood of significant immune dysfunction and may also be associated with the presence of hypothyroidism.
Result
low
T-cell count
Test
T-cell lymphopenia is seen often, although not uniformly. Although not a diagnostic test, detection of T-cell lymphopenia supports the diagnosis of DiGeorge syndrome.
T- (CD3, CD4, CD8) and B- (CD20) cell subsets are routinely enumerated by flow cytometry in most clinical laboratories.
Most patients have some degree of T-cell lymphopenia, usually not severe enough to cause clinical symptoms.[69] Profound T-cell dysfunction is rare, but when present requires immune reconstitution through thymic transplantation or adoptive transfer of mature T cells.
One study proposes using the thymic to thoracic ratio as a screening parameter to identify newborns who require evaluation for 22q deletion.[70]
Result
low
chromosomal microarray analysis
Test
The preferred testing method for patients with suspected DiGeorge syndrome as it can detect small deletions, and can do so across the whole genome.[16][51][52]
Has an advantage over multiplex ligation-dependent probe amplification (MLPA) and fluorescence in situ hybridisation (FISH) which only detect copy number variants within limited genomic regions.
When positive, a loss of one copy is seen at the 22q11.2 locus.
Result
positive
multiplex ligation-dependent probe amplification
immune-specific titres (if previously immunised)
Test
Patients who have been immunised should have positive titres. Absence of positive titres to immunisations suggests T-cell-mediated immunodeficiency.
Result
may be absent
FBC
Test
Lymphopenia may be present.
Result
abnormal
TSH
Test
Should be checked initially and at least yearly, as there is a risk of thyroid dysfunction.
Result
may be high
free T4
Test
Should be checked initially and at least yearly, as there is a risk of thyroid dysfunction.
Result
may be low
chest x-ray
Test
DiGeorge syndrome is characterised by failure of development of a thymus gland.
Result
absent thymus
ECG
Test
The QT interval may be prolonged if hypocalcaemia is present.
Result
may show prolonged QT interval
serum immunoglobulins
Test
In addition to T-cell lymphopenia, may have immunoglobulin deficiency.
Result
may be low
Investigations to consider
fluorescence in situ hybridisation
Test
Typically used in settings where chromosomal microarray analysis (CMA) and multiplex ligation-dependent probe amplification (MLPA) are both unavailable.[52] Detects copy number variants within limited genomic regions.
Two fluorescent spots should be seen if the microdeletion is not present. If only one is seen, the patient person is hemizygous at TUPLE1.
Result
1 copy of probe per cell confirms 22q11.2 deletion
karyotype
Test
Unable to detect 22q11.2 deletion, except in rare translocations. However, it may support identification and diagnosis of other genetic abnormalities.[16]
Result
may detect other genetic abnormalities
echocardiogram
Test
Some heart defects are associated with DiGeorge syndrome, including type B interrupted aortic arch, tetralogy of Fallot, and truncus arteriosus defect.
Result
abnormal structural heart disease
renal and bladder ultrasound
Test
Urinary tract disorders may be seen, which may require consultation from a specialist.
Patients frequently have renal anomalies, including obstruction, dysplasia, and reflux.
Result
renal agenesis or obstruction
audiometry
Test
Hearing disorders may be seen, which may contribute to delayed speech development and learning disability.
Result
abnormal
dental and palatal evaluations
Test
Evaluation for velopharyngeal insufficiency, cleft palate, or submucous cleft.
Nasopharyngeal endoscopy may be required to adequately identify palatal abnormalities.[56]
Result
may show typical abnormalities
ophthalmology evaluation
Test
Coloboma of the eye may be seen in some patients. Patients with CHARGE syndrome will also present with heart defects, atresia of the nasal choanae, retardation of growth and/or development, genital and/or urinary abnormalities, and ear abnormalities and deafness.
Result
may show coloboma of the eye
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