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Centre for Arab Genomic Studies A Division of Sheikh Hamdan Award for Medical Sciences The Catalogue for Transmission Genetics in Arabs CTGA Database 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 Copyright © Centre for Arab Genomic Studies 1 4 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 Copyright © Centre for Arab Genomic Studies 2