DIGEORGE SYNDROME

RUPESH MOHANDAS
GR 3
• Elizabeth Bennet – 7 y/o

• She was born at term after an uncomplicated pregnancy with a low birth weight of 2.1 kg
and dysmorphic facial features were noted , including low-set ears as well as a relatively
small mouth with an undersized lower jaw.

• At 2 days old she developed feeding difficulties, rapid breathing, increased fatigue, and a
bluish discoloration of the skin.

• She was diagnosed with truncus arteriosus and underwent cardiac surgery and
hypocalcemia which was treated with calcium and vitamin D.
 When genetic studies were done, these revealed normal karyotype. But with the help of
fluorescence in situ hybridization (FISH), she was found to have a deletion of chromosome
22q11.2 with a diagnosis of DiGeorge syndrome.

 At 2 weeks old, her absolute lymphocyte count was low for her age, with 560 cells µl-1 (normal
3000 lymphocytes µl-1).

 She had almost no CD3+ T cells.

 Her significant T-cell defect led to the diagnosis of complete DiGeorge syndrome, a rare variant of
DiGeorge syndrome that is associated with severe immunodeficiency and death if not treated
early in life.
 At 6 months of age she received a thymic transplant into her right leg quadriceps muscle.

 One year after transplantation she developed a significant number of T cells, although she
did not reach normal T cell count.

 At 6 years old she developed purple bruises(purpurs) and pinpoint lesions on her skin. She
was found to have low platelet count, due to destruction of her platelets by her
autoantibodies (immune thrombocytopenia)

 She was successfully treated with high-dose intravenous gamma globulin.

 DIGEORGE SYNDROME

It is often referred to as 22q11.2 deletion syndrome.

A condition in which small portion of chromosome 22 is deleted which

causes a bunch of developmental abnormalities and complications.

It is classified as microdeletion since less than 5 million base pairs are
present.

Autosomal dominant immunodeficinecy.

22q11.2 portion of dna spans about 30 genes
and 1.5 – 3 million base pairs.

This region encodes for some really important

genes.

One of which is TBX1 gene which plays a big

role in this disease.
TBX1 gene is involved in normal development of pharyngeal
pouches, specifically pouch 3 and pouch 4.
These are fetal structures that develop into parts of the
head and neck.
Pouch 3 develops into thymus and inferior parathyroid
gland.
Pouch 4 develops into superior parathyroid gland.
So with the 22q11.2 deletion there wont be TBX gene and
thymus and parathyroid gland both end up underdeveloped
( hypoplasia).
T-lymphocytes or T-cells are immune cells that are super important for
the adaptive immune response.
Produced in bone marrow but mature in thymus .
Someone with thymic hypoplasia and thymic dysfunction, the T-cells
don’t mature and people will have deficiency in mature T-cells.

Partial DiGeorge syndrome Complete DiGeorge syndrome

• Mild to moderate dysfunction • Severe dysfunction

• Can be fatal, due to severely

• Immunodeficiency is not life
compromised immune
threatening.
system.
Parathyroid glands secrete PTH, which
helps to increase level of calcium ions
in blood.
Parathyroid hypoplasia leads to low
levels of PTH which causes low levels
of calcium ions in blood
(hypocalcemia).
COMPLICATIONS

Common problems that occur with 22q11.2 deletion syndrome

include:
Congenital heart defects such as Ventricular septal defect,
Truncus arteriosus, Tetralogy of fallot.

Facial abnormalities

1. Cleft palate with or without cleft lip.

2. Distinct facial features. These may include
o small, low-set ears
o short width of eye openings (palpebral
fissures)
o hooded eyes
o a relatively long face
o an enlarged nose tip (bulbous) or
o a short or flattened groove in the upper
lip.
 Learning, behavioral and mental health problems - problems with development and
function of the brain, resulting in learning, social, developmental or behavioral
problems.

• Delays in toddler speech development and learning difficulties are common.

• Later in life, the risk of depression, anxiety disorders and other mental health
disorders increases.
 Autoimmune disorders. People who had poor immune function as
children, due to a small or missing thymus, may also have an increased
risk of autoimmune disorders

1. Idiopathic thrombocytopenia purppura (antibodies against platelets)

2. Autoimmune haemolytic anemia ( antibodies against red blood cells)

3. Autoimmune arthritis or Graves' disease.

 DIAGNOSIS
Diagnosis of DiGeorge syndrome can be difficult due to the number of potential symptoms
and the variation in phenotypes between individuals.

 Genetic analysis is normally performed using fluorescence in situ hybridization (FISH),

which is able to detect microdeletions that standard karyotyping miss.

 Newer methods of analysis include Multiplex ligation-dependent probe

amplification assay (MLPA) and quantitative polymerase chain reaction (qPCR), both
of which can detect atypical deletions in 22q11.2 that are not detected by FISH.

 Array-comparative genomic hybridization (array-CGH) screen the entire genome for

deletions or duplications. It can be used in post and pre-natal diagnosis of 22q11.2
TREATMENT
Although there is no cure for DiGeorge syndrome,
treatments can usually correct critical problems, such as a
heart defect or cleft palate.

 Hypoparathyroidism can usually be managed with

calcium supplements and vitamin D supplements.

 Most heart defects associated with 22q11.2 deletion

syndrome require surgery soon after birth to repair the

heart and improve the supply of oxygen-rich blood.

 Thymus transplantation can be used to address absence of the thymus in
the rare, so-called "complete" DiGeorge syndrome.

 Bacterial infections are treated with antibiotics.

 A cleft palate or other abnormalities of the palate and lip can usually be
surgically repaired.

 Treatment may be recommended if the child is later diagnosed with

attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder,
depression, or other mental health or behavioral disorders.
 REFERENCES

osmosis.org/learn/DiGeorge_syndrome
mayoclinic.org/diseases-conditions/digeorge-
syndrome/symptoms-causes/syc-20353543
primaryimmune.org/about-primary-
immunodeficiencies/specific-disease-types/digeorge-syndrome
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