A comprehensive investigation was undertaken by searching Medline and PubMed for English language publications. The search included papers published up to Sept 30, 2006. The search terms included “epidemiology”, “thymus”, “immune deficiency”, “velocardiofacial syndrome”, “DiGeorge syndrome”, “chromosome 22”, and “TBX1”. Combinations of search terms were also used. To limit the number of references, only a subset of relevant articles were selected.
SeminarVelocardiofacial syndrome, DiGeorge syndrome: the chromosome 22q11.2 deletion syndromes
Introduction
The nomenclature of the velocardiofacial syndrome, known as chromosome 22q11.2 deletion syndrome, has become confusing because many clinical syndromes are associated with a hemizygous deletion of chromosome 22q11.2. 35–90% of patients clinically diagnosed with DiGeorge syndrome (cardiac anomalies, hypoparathyroidism, immunodeficiency) and 80–100% with velocardiofacial syndrome (pharyngeal dysfunction, cardiac anomaly, dysmorphic facies) have the hemizygous deletion.1, 2, 3, 4, 5, 6, 7, 8 Additionally, some patients with CHARGE (coloboma, heart, atresia, retardation of growth, genitourinary problems, ear abnormalities) and conotruncal anomaly face syndromes have the deletion. The reason for the confused nomenclature is the enormous phenotypic heterogeneity of this syndrome (table 1). Here, the term chromosome 22q11.2 deletion syndrome is used when referring to patients who have the deletion, and specific syndromic nomenclature is used when the resource data rely on clinical features.
Chromosome 22q11.2 deletion syndrome is seen in one in 3900 to one in 9700 children,9, 10 and babies are born typically with a conotruncal cardiac anomaly and mild-to-moderate immune deficiency. Developmental delay, facial dysmorphia, palatal dysfunction, and feeding difficulties are also seen in most infants with the syndrome. Other clinical features (table 1) are noted less consistently. Despite the diversity of clinical features, nearly all patients will benefit from coordinated multidisciplinary care. Here, we address some of the most common medical issues of velocardiofacial syndrome and review recent insights into its pathophysiology.
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Epidemiology and genetics
Population-based estimates of the incidence and prevalence of chromosome 22q11.2 deletion syndrome are very different. One of the most-widely cited estimates is that of Wilson and colleagues,11 who calculated a minimum prevalence rate of one in 4000 livebirths on the basis of the presence of the deletion in 5% of patients with congenital cardiac defects. Most estimates come from surveys of one institution or clinic. Goodship and colleagues10 examined 207 infants with congenital heart defects
Diagnosis
Diagnosis is generally straightforward. Most patients with a clinical phenotype of velocardiofacial syndrome or DiGeorge syndrome have a hemizygous deletion of chromosome 22q11.2. The FISH method is accurate, but often takes 2–3 days and is expensive. Efforts to develop a rapid PCR-based method are underway and might result in a commercial test soon.20, 21, 22 Diagnosis becomes more confused when a patient with classic features of velocardiofacial syndrome has no evidence of deletion by FISH. A
Pathophysiology
The disease mechanisms of chromosome 22q11.2 deletion syndrome can be seen from two perspectives. One is the mechanism that underlies the deletion, and the other is the mechanism by which the deletion leads to the clinical phenotype. Since 1993, the deletion has been linked to low copy number repeats (LCRs).39 Four discrete blocks of LCRs are present in this region, and every block consists of several modules of repeats that have various lengths and orientations within a block.40 These blocks
Management
The management of patients with chromosome 22q11.2 deletion syndrome is highly dependent on age and phenotype (figure 5). Few prospective studies support a specific management style. Here, we describe common strategies for each organ system. Patients with the chromosome 22q11.2 deletion syndrome might present at any age, although most patients receive their diagnosis shortly after birth because of the presence of a cardiac anomaly. In newborn babies, a thorough physical and radiographic
Search strategy and selection criteria
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