DiGeorge syndrome: part of CATCH 22.

Abstract

DiGeorge syndrome (DGS) comprises thymic hypoplasia, hypocalcaemia, outflow tract defects of the heart, and dysmorphic facies. It results in almost all cases from a deletion within chromosome 22qll. We report the clinical findings in 44 cases. We propose that DiGeorge syndrome should be seen as the severe end of the clinical spectrum embraced by the acronym CATCH 22 syndrome; Cardiac defects, Abnormal facies, Thymic hypoplasia, aeft palate, and Hypocalcaemia resulting from 22qll deletions. (J7 Med Genet 1993;30:852-6) In 1965 DiGeorge described a child with hypoparathyroidism and recurrent infections along with three necropsy cases of absent thymus and parathyroid glands at an immunology meeting.' The phenotype of the syndrome that was named after him was widened to include congenital heart disease and facial dysmorphism. The first clue to the aetiology of DGS came when de la Chapelle reported a family with a chromosome translocation, t(20;22)(ql1;q 1), in which four subjects with unbalanced products had DGS.2 It is now well established that the vast majority of cases result from deletions within chromosome 22q 1.5 Here we report the phenotypic features in our series of 44 cases of DGS and set this in the broader clinical context of 22ql 1 deletions, for which we now propose the acronym CATCH 22 syndrome.

Tbx1 regulation of myogenic differentiation in the limb and cranial mesoderm

“…Deletion of TBX1 has been linked to the majority of the abnormalities that occur in DiGeorge syndrome (DGS), which encompasses the facial region, derivatives of the branchial arches such as the thymus and parathyroid glands, and vascular/cardiac defects. DiGeorge syndrome affects approximately 1 in 4,000 births and is due to a 22q11.2 deletion, the most frequent chromosomal deletion in humans (Wilson et al, 1993;McDonaldMcGinn et al, 1997;Ryan et al, 1997;Botto et al, 2003). Whereas recent studies have implicated both Tbx1 and the adaptor protein CRK-L in the pathogenesis of this syndrome, point mutations in TBX1 in humans result in similar abnormalities, which is strongly suggestive that haploinsufficiency of TBX1 plays a major role (Yagi et al, 2003;Guris et al, 2006;Paylor et al, 2006).…”

Deletion mapping on chromosome 10p and definition of a critical region for the second DiGeorge syndrome locus (DGS2)

“…It is characterised by an absent or hypoplastic thymus with T-cell deficiency, absent or hypoplastic parathyroid glands with hypoparathyroidism and hypocalcaemia, conotruncal heart defect, craniofacial dysmorphism, and mental retardation. 1,2 More than 90% of patients with DGS have a microdeletion of 22q11 (DGS1). 3,4 The associated phenotypes are variable, with a large proportion of patients exhibiting only a subset of the above mentioned traits.…”

Auxological evaluation in patients with DiGeorge/velocardiofacial syndrome (deletion 22q11.2 syndrome)

“…[3][4][5] Growth retardation is reported in 36% of the patients included in the European collaborative study, 5 and in 39 -63% of the patients with a clinical diagnosis of DG/VCF syndrome in the series collected before the advent of the microdeletion studies. 1,6 -8 Growth hormone deficiency has been detected in 4 patients from the literature presenting with extreme short stature, two of whom had pituitary anomalies.…”