Immunodeficiency Due to Insufficiency

of the Cellular Link of the Immune

System: DiGeorge Syndrome
I. DiGeorge Syndrome as a specific form of immunodeficiency:
 DiGeorge Syndrome is a genetic disorder that affects multiple organ systems, including the
immune system.
 Characterized by the partial or total absence of the thymus gland, leading to impaired T-
cell development and dysfunction.
 T-cells play a crucial role in adaptive immunity, and their deficiency in individuals with
DiGeorge Syndrome results in immunodeficiency and increased susceptibility to
infections.
II. Genetic basis (chromosome 22q11.2 deletion), T-cell developmental
disruption:

 DiGeorge Syndrome is primarily caused by a deletion on chromosome 22q11.2

affecting genes that are critical for thymus development and T-cell maturation.
 The absence or underdevelopment of the thymus gland impairs the production of
functional T-cells, which are essential for recognizing and fighting off pathogens.
 This disruption in T-cell development leads to an inadequate immune response and
III. Impact on immune response and susceptibility to infections:

T-cells play a central role in

coordinating immune defense
mechanisms, including antigen
recognition, activation of other
immune cells, and production of
antibodies.

The lack of T-cells compromises the

adaptive immune system's ability
to mount an effective response
against invading pathogens, making
individuals with DiGeorge Syndrome
more susceptible to recurrent
infections, including bacterial, viral,
and fungal diseases.

The compromised immune

The absence of a functional thymus
response also affects the body's
gland and deficient T-cell population
ability to control and eliminate
in individuals with DiGeorge
pathogens, leading to chronic and
Syndrome significantly impacts
severe infections in affected
their immune response.
individuals.
 Immunopathogenesis of DiGeorge Syndrome:
Step 1: DiGeorge Syndrome is
caused by a microdeletion in
chromosome 22q11.2, Critical
genes within this region, including
TBX1, are involved in thymic
development.
• Markers: Fluorescence in situ hybridization
(FISH) or polymerase chain reaction (PCR)
can be used to detect the chromosome
22q11.2 deletion.
Step 4: Impaired T-cell Maturation,
Normal T-cell maturation involves
migration from the bone marrow to the
thymus for selection processes, In
DiGeorge Syndrome, abnormal thymic
development impairs proper T-cell
maturation and functionality.
• Markers: Immunophenotyping to evaluate T-cell
function and immune response markers such as
interleukins and cytokines.
Step 2: Thymic Development,
During embryonic development,
the thymus gland arises from the
third pharyngeal pouch, The
microdeletion affects the
migration and differentiation of
thymic epithelial cells.
• Markers: Imaging techniques such as
ultrasound or MRI can assess thymic size
and structure.
Step 5: Compromised Adaptive
Immunity, Deficient T-cells impair
adaptive immune responses and
increase susceptibility to infections.
• Markers: Comprehensive immunological
profiling to assess T-cell function and immune
response markers.
Step 3: Thymic Aplasia/Hypoplasia
and T-cell Development
• Thymic Aplasia: Complete absence of the
thymus gland.
• Thymic Hypoplasia: Underdevelopment of
the thymus, leading to reduced T-cell
production.
• Markers: Flow cytometry to assess T-cell
subsets and markers, including CD3, CD4,
and CD8.
Step 6: Disrupted T-cell development
leads to immune system imbalance and
dysfunction. Overall immune function is
compromised, affecting the body's
ability to mount effective immune
responses.
• Markers: Immunological profiling, including
immune cell subsets, cytokines, and immune
response markers, can provide insights into the
disrupted immune system link in individuals
with DiGeorge Syndrome.
V. Clinical Manifestations of DiGeorge Syndrome

Congenital Heart Disease Abnormal Facies Thymic Hypoplasia

(primarily conotruncal
anomalies)
• Congenital heart disease is a common
feature of DiGeorge Syndrome, with
conotruncal anomalies such as
tetralogy of Fallot and interrupted
aortic arch being frequently observed.
• The reason for this manifestation is the
deletion in chromosome 22q11.2,
which impacts the development of
cardiac structures during
embryogenesis.
(hypertelorism, low set ears,
short philtrum, among
others)
• Abnormal facial features, including
hypertelorism (wide-set eyes), low set
ears, and a short philtrum, are
characteristic signs of DiGeorge
Syndrome.
• These facial dysmorphisms are linked
to the genetic deletion in chromosome
22q11.2, which affects craniofacial
development in utero.
• Thymic hypoplasia, resulting in
underdevelopment of the thymus
gland, is a key component of DiGeorge
Syndrome.
• The genetic deletion in chromosome
22q11.2 affects the migration and
differentiation of thymic epithelial
cells, leading to thymic hypoplasia and
subsequent T-cell deficiency.
V. Clinical Manifestations of DiGeorge Syndrome

Cleft Palate/Cellular Immune Deficiency

• Cleft palate and cellular immune deficiency are
associated features of DiGeorge Syndrome.
• The deletion on chromosome 22q11.2 affects the
development of both the palate and immune system,
resulting in cleft palate formation and impaired T-cell
function.

Hypoparathyroidism with Hypocalcemia

• Hypoparathyroidism, characterized by low levels of
parathyroid hormone and hypocalcemia, is commonly
observed in individuals with DiGeorge Syndrome.
• The genetic deletion on chromosome 22q11.2 impacts
the development of the parathyroid glands, leading to
hypoparathyroidism and calcium regulation
abnormalities.
VI. Treatments and management of DiGeorge Syndrome

The goal of treatment is to address the specific symptoms and complications

associated with the syndrome and improve the overall quality of life for
individuals affected by it.

Addressing immune-related issues, such as T-cell deficiency and recurrent

infections. Individuals with DiGeorge Syndrome are at a higher risk of developing
infections due to their impaired immune function.

• Treatment of infections with antibiotics and antifungal medications, are essential in managing these
immune-related complications.
• Immunoglobulin replacement therapy may be recommended for individuals with significant immune
deficiencies to improve immune function and reduce the frequency of infections.
surgical interventions to correct congenital heart defects and cleft palate, as well
as ongoing management of hypoparathyroidism with calcium and vitamin D
supplementation to maintain proper calcium levels in the body. Thymus
transplantation may be considered for patients with severe thymic dysfunction to
improve immune function.

management of hypoparathyroidism with calcium and vitamin D supplementation

to maintain proper calcium levels in the body.
Спасибо за внимание!
Prepared by: Asaad Ward