genetic disorder of DiGeorge syndrome was primarily described in by the
paediatrician Angelo DiGeorge 1968 as an immunodeficiency from a impaired
growth of pharyngeal pouches, Other names for the same condition
are Velo-Cardio-Facial Syndrome and Shprintzen Syndrome – The name confusion
arose because different researchers each described parts of the very broadened
image that are caused by deletion 22q11.2.
.Its frequency in the population is an estimated 1 :
3000 live births it is the most common deletion syndrome that has been
Digeorge syndrome also referred to as 22q11.2 deletion
syndrome this results in an embryological problems when the foetus is
developing it affects pharyngeal pouches particularly 3 and 4 this is something
that happens during the first 8 weeks of foetus gestation .This describes a
condition in which a small portion of chromosome 22 is deleted which causes
developmental abnormalities and complications.
22q11.2 refers to chromosome 22 ,q denotes the long
arm and its on region 1 band 1 and sub-band 2, this portion spans 30 genes and
1.5 to 3 million base pairs therefore this classifies it as a micro deletion as
its less than 5 million base pairs.
even though this region is relatively small it codes
for some very important genes one of which is TBX1 gene which plays a major
role in the development of the disease.
The TBX1 gene is involved in normal development of the
pharyngeal pouches , specifically pouch 3 and 4 which are foetal structures
that develop into parts of the head and neck.
The third pharyngeal pouch goes on to develop into the
thymus and the inferior parathyroid gland , the fourth pouch goes on to develop
into the superior parathyroid gland.
So with a 22q11.2 deletion and therefore no TBX1 gene
, the thymus and parathyroid gland end up being underdeveloped this is called
T lymphocytes or T cells are immune cells that are
super important for the adaptive immune response that are produced in the bone
marrow but mature in thymus so if someone has thymic hypoplasia and thymic
dysfunction , the T cells do not mature , and these people have a deficiency in
mature t cells.
Most people with Digeorge syndrome have mild to
moderate thymic dysfunction called partial digeorge syndrome , which means
immunodeficiency isn’t life threatening , however complete digeorge syndrome
can be fatal in first year of life due to severely compromised immune system.
The parathyroid glands is the other organ that is
affected by digeorge syndrome , it secretes parathyroid hormone which increases
level of calcium ions in the blood. Parathyroid hypoplasia leads to low levels
of parathyroid hormone , which causes low levels of calcium ions in the blood
called hypocalcaemia , this may also result in seizures in the first stages of
the childs life.
In addition to affecting the thyroid and parathyroid
glands and causing hypoplasia , the 22q11.2 region encodes genes that may
affect other organs and tissues , individuals with 22q11.2 deletion syndrome
commonly have congenital heart defects typically conotruncal deficiencies , in
particular truncus arteriosus and tetralogy of Fallot , as well as facial
abnormalities like a cleft palate and a characteristic ‘facies’ which means
they have many abnormal fascial features such as a long face , small teeth or a
broad nose . these become characteristic facies of digeorge syndrome.
Patients might have high rates of behavioural and
mental health conditions like schizophrenia. There are large
individual variations among persons with velocardiofacial syndrome
(VCFS). Many also have lip / palpitations and disorders in the palate,
throat and mouth motor function, as well as kidney and urinary tract
malformations. Motor development and speech and language development are
often delayed. Cognitive abilities usually lie in the lower part of the
normal area or in the area of ??mild developmental disability.
To diagnose DiGeorge syndrome may be difficult however
it may be done by genetic testing if it is suspected ,however this may only be
found using the FISH method (fluorescence IN Situ Hybridization) , also other
blood tests looking at T cell numbers and function , calcium and parathyroid
hormone can also be helpful.
As this syndrome is due to a genetic deletion there is
no known cure , though many of the symptoms can be treated and managed so we have
various goals to manage the repercussions of this syndrome such as to correct
any anatomical defects such as abnormalities in the heart and the palate , we
also aim to correct any possible hypocalcaemia , correct various functional
problems such as those in the immune system , speech or the VPI another example
may be infections due to immunodeficiency might be treated with antibiotics ,hypercalcaemia
can be managed with vitamin D and calcium supplements.
Possible complications of this syndrome depend on the
problems that are present and the early diagnosis such as heart disease and
heart failure , untreated hypocalcaemia may cause cramps , there may also exist
serious infections of severe immune deficiency and neurological complications
in brain formation.
However surgery might be required for more complicated
cases such as thymus transplant for severe DiGeorge syndrome or heart surgery for
children with congenital heart defects. Surgery may also be performed on the
lips and palate. Cardio logical , endocrinological , immunological and
neurological treatment and follow – up. In numerous cases people need speech
therapists due to speech difficulties and delayed language development.
As we have already previously mentioned this syndrome
is caused by a chromosomal aberration , which is caused by a structural
This is a an autosomal dominant genetic disorder
meaning that if one of the parents is affected by such an aberration then there
is a 50% chance that the child will get the syndrome. The vast majority of cases (about
90%) are due to new mutation, that is, the change in the chromosome pair has
developed in this individual. In 10% of the people with the syndrome, the
chromosomal defect is inherited from one of the parents.
The European DiGeorge syndrome database currently lists 181 different
symptoms or malformations that are certainly linked to the syndrome – but each
patient has only a few of them. Because a large proportion of the people
who carry deletion 22q11.2 are not ill, there are approximately 7% of the
children with DiGeorge syndrome who inherited chromosomal failure from one of
Due to the widespread affect of this disorder it must
be differentiated from other forms of diseases primarily from congenital heart
disease , infection trend , hypocalcaemia , fascial malformations , delayed
development , palpitations , ear deformities , deafness and malformations in the aortic arch along with speech
Over 90% of children with DiGeorge syndrome have
“open snow” which means that they have difficulty in pronouncing the
“hard” sounds – k, p, t. This is because the soft palate does not
close properly between the nose and mouth when the child speaks. Some of the
children have an actual cleft palate completely at the rear of the soft palate.
While the children are tired, the leakage between the
nose and mouth may cause milk and other food .To run into the nose – it is very
uncomfortable for the child and inhibits the child’s desire to eat.
The nose root is relatively wide, the eyes are quite far apart and the
ears are low. People with VCFS often have a small, “sweet” mouth
and their eyes can be almond shaped. The symptoms that are commonly
referred to as Catch22 as it is the symptoms that lead to the diagnosis of the
condition. Nevertheless, it is important to pay attention to the various
issues that may arise.