DiGeorge syndrome (DGS) belongs to a group of phenotypically similar disorders which share a microdeletion at band 22q11.2.
One of the most common reasons to suspect DGS is the presence of a conotruncal cardiac anomaly. Neonatatal hypocalcemia will also bring about suspicion of this syndrome especially in cases where the heart defect or hypocalcemia is coupled with a cleft palate . This is often seen in affected individuals. Equally, pediatric severe immune deficiency is good reason to suspect this syndrome as well.
The characteristics of this syndrome are not obvious in infancy as they are not fully manifested until the child is a bit older. The distinctive facial features many be subtle or even absent especially in people who are not ethnic whites.
Delay in development may not be overly visible in infancy. It can also remain unnoticed until the child has attained school age.
In nearly 40% of patients, feeding difficulty is present. These difficulties may be due to nasal regurgitation arising from a submucous cleft palate. Swallowing difficulties often clear up with the first year leaving the child with hypernasal speech as manifestation. Dysmotility and abnormality of the oropharyngeal and cricoesophagheal swallowing phase may bring about abnormal swallowing (with aspiration in many cases).
To evaluate DiGeorge syndrome, some of the laboratory studies carried out include multiplex ligation-dependent probe amplification (MLPA), TBX1 gene sequencing or TBX1 deletion/duplication analysis, fluorescent in situ hybridization (FISH) and array comparative genomic hybridization (aCGH) .
Radiography and MRI, CT scanning, Echocardiography and Angiography are some of the imaging studies carried out.
Treatment depends on the associated abnormalities and may include heart surgery, speech therapy, nasogastric feeding, calcium supplementation, and thymus transplantation or adoptive transfer of mature T cells.
The prognosis for this condition varies a great deal depending on the nature and level of involvement of the different organs. Majority of adults with this condition live a long and productive life .
The major cause mortality with this condition is severe immune deficiency and congenital heart defect. This explains why mortality is higher in infants. Infants with thymus aplasia suffer severe immunodeficiency. They typically die of sepsis, which is usually due to bacterial or fungal infections.
As stated earlier, the condition is triggered by part of chromosome 22. Every individual has two copies of this chromosome with one coming from each parent. The chromosome has 500 to 800 genes on average.
With DGS, a copy of the chromosome 22 will be short a segment housing an average of 40 genes. Many of these genes are yet to be clearly identified or well understood . The deletion of genes from the chromosome 22 occurs randomly in the father’s sperm or mother’s egg. In some cases it occurs early into development. This means that deletion will be repeated in all of the cells in the body as the fetus continues to develop.
According to estimates, DGS occurs between 1 per 2000 to 1 per 4000 individuals in the general population of the world. It is one of the most common causes of cleft palate and most congenital heart defects.
Even though DGS is a congenital condition, the age at which it becomes visible to diagnosis is dependent on the type of defect it causes and its severity . Therefore, patients who have hypocalcemia and other more serious cardiac defects are diagnosed within the neonatal frame. In patients older than 3-6 months, recurrent infections are visible in patients that are older than 3-6months.
People who have normal immune function without hypocalcemia, mild cardiac defects, and very little facial anomalies may stay undiagnosed until late into childhood. There have been cases of diagnosis in adulthood and these are mostly reported in individuals with mild symptoms that are isolated . There have been frequent prenatal diagnosis of fetuses with congenital heart conditions so pregnant women at risk of giving birth to children with this defect should be closely monitored.
Deletion of this portion of the chromosome triggers a range of embryonic developmental disruptions which often involve the kidneys, skeleton, brain, neck and head. Parts of the heart, head and neck, thymus, and parathyroids arise from the third and fourth pharyngeal pouches and as a result of the chromosomal deletion, a developmental field defect occurs . This leads to variable T-cell deficiency and hypocalcemia.
The size of the most common deletion seen in over 80% of cases is 3 million base pair. It encompasses 4 micro RNAs and 40genes. Among these genes is the TBX1 gene which is suspected to play a major role in the typical symptoms of this condition. There have not been any proofs of genotype-phenotype correlation.
Mode of inheritance
Since the condition is as a result of noninherited deletion its occurrence is sporadic in majority of cases (over 90%).
Only 10% of individuals have inherited this deletion from a parent as an autosomal dominant condition. The involvement of siblings has only been diagnosed when chromosome 22 deletion was found in a parent.
An affected individual has a 50% chance of transmitting this condition to his or her child. There have also been reports of wide intra and interfamily variability in the clinical manifestation of this condition.
There are no guidelines for prevention of DiGeorge syndrome.
DiGeorge syndrome is a genetic condition known by other names such as DiGeorge anomaly, 22q11.2 deletion syndrome, velo-cardio-facial syndrome, Shprintzen syndrome, conotruncal anomaly face,strong syndrome, thymic hypoplasia and congenital thymic aplasia .
It is caused by the deletion of a small portion of chromosome 22. The deletion takes place towards the middle of the chromosome at a location designated as 22q11.2. The designation shows that the deletion occurs on region 1, band 1, sub-band 2 of the long arm of one of the pair of chromosomes 22.
This syndrome was first described in 1968 by Angelo DiGeorge, a pediatric endocrinologist. The condition is with truncus arteriosus also associated with truncus arteriosus .
Genetic counselling is vital so that parents will be fully aware of the recurrence risk of DiGeorge syndrome.
The families of individuals with significant immunodeficiency equally have to be educated on the potential complications that can arise due to exposure to poliovirus vaccine, MMR vaccine, and chicken pox vaccine that is live attenuated .