22q11 deletion syndrome is a rare congenital disease associated with recurrent infections, heart defects, facial abnormalities and excess rates of psychopathology.
Has several presentations including DiGeorge syndrome, DiGeorge anomaly, velo-cardio-facial syndrome, Shprintzen syndrome, conotruncal anomaly face syndrome, Strong syndrome, congenital thymic aplasia, and thymic hypoplasia is a syndrome caused by the deletion of a small piece of chromosome 22.
Deletion occurs near the middle of the chromosome at a location designated q11.2 i.e., on the long arm of one of the pair of chromosomes 22, on region 1, band 1 , sub-band 2.
Inherited in an autosomal dominant pattern.
DiGeorge syndrome is a genetic disorder caused by the deletion of a small section of chromosome 22, and results in a midline congenital defect including thymic aplasia, or congenital deficiency of a thymus.
Patients with DiGeorge syndrome may present with a profound immunodeficiency disease, due to the lack of T cells.
DiGeorge syndrome is the most common congenital cause of thymic aplasia in humans.
The syndrome can be inherited, but is responsible for a minority of newly diagnosed individuals.
Only 5–10% have inherited the 22q11.2 deletion from a parent, whereas about 90–95% of cases have a de novo deletion of 22q11.2.
Prenatal testing, via amniocentesis, is available for pregnancies determined to be at risk.
Pregnancies with findings of congenital heart disease and/or palate anomalies detected by ultrasound examination may be offered prenatal testing.
69% of children have palatal abnormalities.
Most patients with 22q11.2 deletion syndrome are missing about 3 million base pairs on one copy of chromosome 22 in every cell.
It has a prevalence estimated at 1:4000.
The features of this syndrome vary widely, even among members of the same family.
Affects many parts of the body.
Characteristics include birth defects such as congenital heart disease, defects in the palate withneuromuscular problems with closure, learning disabilities, mild differences in facial features, and recurrent infections.
Infections are common in children due to an absent or hypoplastic thymus.
22q11.2 deletion syndrome may be first recognized in an affected newborn with heart defects or convulsions from hypocalcemia due to malfunctioning parathyroid glands.
Other kinds of birth defects including kidney abnormalities (37%) may be present.
Feeding difficulties may occur in newborns.
Late occurring processes include hypothyroidism, hypoparathyroidism or thrombocytopia, and psychiatric illnesses are common.
Microdeletions in 22q11.2 are associated with a 20 to 30-fold increased risk of schizophrenia.
About a quarter develop schizophrenia and 30% have acute psychoses.
CATCH-22-refers to Cardiac abnormalities. Abnormal facies, Thymic aplasia, Cleft palate, Hypocalcemia
Congenital heart disease occurs in 40% of individuals, including tetralogy of Fallot, interrupted aortic arch, ventricular septal defect, and persistent truncus arteriosus.
50% have palatal abnormalities, particularly velopharyngeal incompetence,and cleft palate.
Facial feature abnormalities include hypertelorism.
Common problems include hypernasality, language delays, and speech sound errors.
90% have learning disabilities.
50% have hypocalcemia due to hypoparathyroidism.
May be associated with hearing loss, growth hormone deficiencies, autoimmune disorders, seizures, and skeletal abnormalities.
22q11.2 deletion syndrome may involve migration defects of neural crest-derived tissues affecting development of the third and fourth branchial pouches.
It is one of the most common causes of mental retardation due to a genetic deletion syndrome.
Patients usually have a borderline normal IQ.
Most have higher verbal than the nonverbal scores.
Commonly have difficulty acquiring vocabulary, and articulation problems.
Also known as thymic aplasia.
Clinical associated with a triad of hypocalcaemia, tetany and absence of T cells.
Caused by a defect in the formation of third and fourth pharyngeal pouches early in gestation.
Not inherited despite its association with 22q11 chromosomal microdeletions.
Nondevelpoed thymus and absence of a parathyroid gland causing the T cell and calcium deficiencies, respectively.
presentation is neonatal tetany and recurrent infections due to viral and fungal elements.
Facial and cardiac malformations are common.
Patients present with cyanosis from cardiac disease or tetany from hypocalcaemia.
Chest x-ray shows absent or markedly reduced thymic shadow.
Low or undetectable T cells noted in the peripheral blood.
Low levels of circulating immunoglobulins present.
No cure for 22q11.2 deletion syndrome.
In the presence of fragments of thymus gland immunostimulatory agents may increase thymus growth and reconstitute immunity.
Fetal thymic transplantation may be a treatment option.
Treatment results in a good prognosis.