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DiGeorge Syndrome
Alternative Names
DGS
Hypoplasia of Thymus and Parathyroids
Third and Fourth Pharyngeal Pouch Syndrome
DiGeorge Syndrome Chromosome Region
Takao VCF Syndrome
DGCR
Catch 22
22q11.2 Deletion Syndrome
DiGeorge Anomaly
DGA
Microdeletion 22q11
Velocardiofacial Syndrome
WHO International Classification of Diseases
Diseases of the blood and blood-forming organs
and certain disorders involving the immune
mechanism
OMIM Number
188400
Mode of Inheritance
Autosomal dominant
Gene Map Locus
22q11.2
Description
DiGeorge syndrome is a rare congenital primary
immune deficiency disease that includes
symptoms such as abnormal characteristic facial
features, increased susceptibility to infection,
hypoplasia of thymus and parathyroid glands
and cardiomyopathy.
The incidence of
DiGeorge syndrome is in the range of 1 per
3000 births, causing morbidity and mortality
mainly due to congenital heart defect, where
most deaths occur 6 months after birth. The
second most common cause of mortality is
infections due to severe immune deficiency.
The syndrome is frequently progressive to
psychomotor retardation with a 50% chance of
mental retardation.
DiGeorge syndrome is caused by abnormal
development of certain cells and tissues of the
neck during growth and differentiation of the
fetus.
Molecular Genetics
Most patients with DiGeorge syndrome have a
micro deletion from chromosome 22 at position
q11.2, produced by an error in recombination at
meiosis. The symptoms of the disease are
related to the amount of genetic material lost in
the deletion.
Epidemiology in the Arab World
Lebanon
Mansour et al. 2005 conducted a retrospective
study of 240 consecutive patients with
congenital heart disease. The most common
anatomic cardiac anomalies were ventricular or
atrial septal defects (62), tetralogy of Fallot
(39), pulmonary stenosis (25), and transposition
of the great arteries (24). The heart lesions were
divided physiologically into volume overload
(90), cyanotic (87), and obstructive (63). In all,
105 syndromic subjects included the
velocardiofacial syndrome (18), Down's
syndrome (17), CHARGE association (6),
DiGeorge syndrome (5), Williams syndrome
(3), Edwards syndrome (3), Noonan syndrome
(3), VACTERL association (2), and Patau
syndrome (trisomy 13) (2).
Saudi Arabia
Mathew et al. (1986) reported four children with
hypoparathyroidism. Two of the children had
hypoparathyroidism as part of DiGeorge
Syndrome.
In 1999, Iqbal et al. used fluorescent in situ
hybridization (FISH) to diagnose microdeletion
syndromes in 4 patients with Prader-Willi
Syndrome [del(15)(q11.2q12)], 4 patients with
DiGeorge syndrome [del(22)(q11.2q11.23)] and
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patients
with
Williams
syndrome
[del(7)(q11.23q11.23)]. For the diagnosis of
DiGeorge syndrome Iqbal et al. (1999) used the
D22S75 DiGeorge chromosome region probe
with chromosome 15 control probe.
United Arab Emirates
Sztriha et al. (2004) reported two boys with
chromosome 22q11 deletion syndrome and
polymicrogyria. Both patients showed severe
developmental delay with cardiovascular
malformations and one of them had drug
resistant epilepsy. Patient 1 was born to nonconsanguineous parents by Cesarean section
after a pregnancy complicated with gestational
diabetes. The patient developed myoclonic and
generalized tonic clonic seizures, which were
refractory to several antiepileptic drugs. Brain
MRI revealed polymicrogyria in the frontal,
parietal, and temporal areas, unilaterally. Right
functional hemispherectomy was performed
because of intractable epilepsy. The clinical
and radiological findings were suggestive of
22q11 deletion. Chromosomal analysis and
fluorescent in situ hybridization (FISH) with a
DNA probe specific for the DiGeorge syndrome
were performed.
It showed monosomic
microdeletion at 22q11.2. None of the parents
had the deletion. Patient 2 was born post-term
to non-consanguineous parents. Brain MRI
revealed bilateral polymicrogyria in the frontal,
parietal, and temporal areas. Chromosomal
analysis with FISH showed monosomic
microdeletion at 22q11.2. None of the parents
had the deletion. Both patients had serious
delay of mental and motor development. They
also
had
dysmorphic
features
and
cardiovascular abnormalities.Histology revealed
four-layered polymicrogyria.
References
Iqbal MA, Ulmer C, Sakati N. Use of FISH
technique in the diagnosis of chromosomal
syndromes. East Mediterr Health J. 1999;
5(6):1218-24.
Mansour AM, Bitar FF, Traboulsi EI, Kassak
KM, Obeid MY, Megarbane A, Salti HI.
Ocular pathology in congenital heart disease.
Eye. 2005; 19(1):29-34.
Mathew PM, Hamdan JA, Mallouh A, Ahmed
MS. Hypoparathyroidism in Arab children.
Ann Trop Paediatr. 1986; 6(3):187-90.
Sztriha L, Guerrini R, Harding B, Stewart F,
Chelloug N, Johansen JG. Clinical, MRI, and
pathological features of polymicrogyria in
chromosome 22q11 deletion syndrome. Am J
Med Genet A. 2004; 127(3):313-7.
Contributors
Ghazi O. Tadmouri: 5.12.2005
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